partnership for success with huntington’s wa€¦ · school of medical sciences, ... psychiatric...
TRANSCRIPT
Partnership for Success with Huntingtonrsquos WA
AIMS
1 To ameliorate symptoms and improve quality of life
2 TO CHANGE POLICY and PRACTICE IN PATIENT CARE
VERY GENEROUSLY FUNDED BY LOTTERYWEST
Can rehabilitation help people with
early-mid stage Huntingtonrsquos
disease
M Ziman J A Thompson T Cruickshank A Reyes Z Khan L Penailillo R A Barker SR Davies S Andrew J
Lee A Hannan R Newton School of Medical Sciences Edith Cowan University Perth WA Cambridge Centre for Brain Repair Cambridge University UK
Neurosciences Unit Department of Health North Metropolitan Area Perth WA Howard Florey Institute University of Melbourne Melbourne VIC
Launch March 2010
Huntingtonrsquos
disease (HD)
Inherited Neurodegenerative
Disorder
Mutation in the Htt gene
50 chance of inheritance if either
parent has the mutated gene
Onset ndash 30-70 years of age
Incidence ~57 per 100000 in
Australia
HD is a fatal complex and
severely debilitating disease
for which there is no cure
There is a gradual loss of neural cells and
muscle cells
So gradual loss of cognitive physical
and emotional function
HISTORY
Paracelsus (1527) 16th century
1872 recognized as a disease for first time
Dr George Huntington (New York) published
ldquoOn Choreardquo in The Medical and Surgical
Reporter of Philadelphia
22 years - Sole publication of just a few paragraphs
was entirely anecdotal and unreferenced
1993 the huntingtin protein was inextricably linked
to the huntingtin gene (Htt or IT15) and to the
disease
HOW
Mutation in the Htt gene
Htt gene has C A G repeat in
exon 1
Normal = 9-36 repeats
Mutant gene = 40 -
250
Produces an abnormal protein
with a polyglutamine tract
Length of CAG repeat
correlates with age of onset
(can be as young as 2)
ABNORMAL PROTEIN -
NEURAL LOSS
protein-protein interactions
With normal proteins
Aggregates in cytoplasm
Inclusion bodies in nucleus
bullVesicular Transport Defective
bullGene transcription and expression
affected
NORMAL PROTEIN In nucleus cell body dendrites of many nerve cells
Transcription vesicle transport cytoskeletal anchoring and pro-survival properties
Timed loss of neurons with abnormal HD protein
RESULT
Loss of neurons in specific brain regions
In the striatum (basal ganglia) causing
loss of movement control
In the cortex and cerebellum - causing
Psychosis and Dementia
Loss of brain volume
Striatal neurons
Coordinate complicated motor and
visual and thinking tasks
- Computer games
- Driving a car
Striatal neurons linked to cortical
neurons
Striatum is also
affected in
Parkinsonrsquos disease
Muscle Movement Disorders - CHOREA hyperkinetic - dystonia and rigidity hypokinetic initiating voluntary movements
Chorea Atrophy
Summary of Symptoms Neural Cell Death
Cognitive (Neural)
Symptoms
Muscle Cell Deficits
Motor (Muscular) Symptoms
STRIATUM Loss GABAergic medium spiny neurons
Loss of Executive Function (Planning)
Decreased fibre diameter Reduce neural input
Muscle Atrophy - Gait Dysfunction
CORTEX Pyramidal neurons
Loss of Short Term Memory (Dementia)
Fibre type switching
Chorea
Decreased Creatine Kinase (energy stores)
Psychiatric disturbances (delusionsparanoiaanxiety)
Decreased Creatine Kinase (energy stores)
Saccadic eye movements
Loss of Brain Neurotrophic factor BDNF
Depression Mitochondrial dysfunction - energy
Loss of Balance - Vestibular
Huntingtonrsquos disease is not just a disease of the CNS
Peripheral effects of HD
Weight loss
(Adapted from van der Burg (2009) Lancet Neurology 8 765-774
Need to treat all defects using multi-disciplinary intervention
No treatment is
currently available that
slows alters or
reverses the disease
progression
Treatment of Symptoms
Pharmacological Therapies
Antipsychotics
Benzodiazepines
Dopamine Antagonists
Antidepressants
Antichoreic Agents
NEWER MEDICATION
Glutamate Blockers
antioxidants (Q10)
Nerve Growth Factors
Creatine
Stem Cell and
Foetal Tissue Transplants
IMPROVE
NEUROGENESIS
AS THERAPY
Replacing old or lost neurons with new
neurons
NEUROGENESIS
Upregulated by Mental and Physical
Exercise
Physical stimulation (exercise)
upregulates production of endogenous
stem cells within the brain
Cognitive stimulation increases stem cell
survival and integration of new neurons
Together increased production and
survival of neural stem cells in mouse
models of HD
Environmental enrichment - combined
use of mental and physical stimulation to
effect neurological changes
HEROs (Huntingtons Enrichment Rehabilitation Optimisation Scheme)
AIM Implement Environmental Enrichment Program (HEROS)
bullOUTCOMES Slow progression of Huntingtonrsquos disease
bullUpregulate stem cells within the brain and assist their maturation and integration into the existing brain circuitry bullImprove QOL for people with HD benefits carers and families
bullChange policy and practice for treatment of HD
bullMULTIDISCIPLINARY RESEARCH COLLABORATION neuroscientists neurologists neuroradiologists psychologists and psychiatrists occupational therapists physiotherapists exercise physiologists social workers AND the HD Association
Scientifically validate our research Myriad of assessments
Participant Baseline measures Taken June 2010
1 Psychiatric assessment ndash Clinical UHDRS motor score
2 Occupational Therapy and Physiotherapy assessment
3 MRI Brain Volume and fMRI - Functional Imaging and Mapping
4 Blood Biochemical tests ndash Insulin BDNF Creatine Kinase Salivary Cortisol
5 Physical Movement analyses i Height Weight Muscle Dimensions Composition
ii Muscle Strength ndash Isokinetic Isometric Contractions
iii Gait and Walking
iv Fine Motor and Reaction time
v Balance Prevalence of Falls QOL
MRI and fMRI to measure brain volume and function
Body Composition
Height Weight
Arm and Thigh
measurements
Dexa Scan ndash
Dual Energy X-Ray
Absorptiometry scan
ndash Body Composition
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Can rehabilitation help people with
early-mid stage Huntingtonrsquos
disease
M Ziman J A Thompson T Cruickshank A Reyes Z Khan L Penailillo R A Barker SR Davies S Andrew J
Lee A Hannan R Newton School of Medical Sciences Edith Cowan University Perth WA Cambridge Centre for Brain Repair Cambridge University UK
Neurosciences Unit Department of Health North Metropolitan Area Perth WA Howard Florey Institute University of Melbourne Melbourne VIC
Launch March 2010
Huntingtonrsquos
disease (HD)
Inherited Neurodegenerative
Disorder
Mutation in the Htt gene
50 chance of inheritance if either
parent has the mutated gene
Onset ndash 30-70 years of age
Incidence ~57 per 100000 in
Australia
HD is a fatal complex and
severely debilitating disease
for which there is no cure
There is a gradual loss of neural cells and
muscle cells
So gradual loss of cognitive physical
and emotional function
HISTORY
Paracelsus (1527) 16th century
1872 recognized as a disease for first time
Dr George Huntington (New York) published
ldquoOn Choreardquo in The Medical and Surgical
Reporter of Philadelphia
22 years - Sole publication of just a few paragraphs
was entirely anecdotal and unreferenced
1993 the huntingtin protein was inextricably linked
to the huntingtin gene (Htt or IT15) and to the
disease
HOW
Mutation in the Htt gene
Htt gene has C A G repeat in
exon 1
Normal = 9-36 repeats
Mutant gene = 40 -
250
Produces an abnormal protein
with a polyglutamine tract
Length of CAG repeat
correlates with age of onset
(can be as young as 2)
ABNORMAL PROTEIN -
NEURAL LOSS
protein-protein interactions
With normal proteins
Aggregates in cytoplasm
Inclusion bodies in nucleus
bullVesicular Transport Defective
bullGene transcription and expression
affected
NORMAL PROTEIN In nucleus cell body dendrites of many nerve cells
Transcription vesicle transport cytoskeletal anchoring and pro-survival properties
Timed loss of neurons with abnormal HD protein
RESULT
Loss of neurons in specific brain regions
In the striatum (basal ganglia) causing
loss of movement control
In the cortex and cerebellum - causing
Psychosis and Dementia
Loss of brain volume
Striatal neurons
Coordinate complicated motor and
visual and thinking tasks
- Computer games
- Driving a car
Striatal neurons linked to cortical
neurons
Striatum is also
affected in
Parkinsonrsquos disease
Muscle Movement Disorders - CHOREA hyperkinetic - dystonia and rigidity hypokinetic initiating voluntary movements
Chorea Atrophy
Summary of Symptoms Neural Cell Death
Cognitive (Neural)
Symptoms
Muscle Cell Deficits
Motor (Muscular) Symptoms
STRIATUM Loss GABAergic medium spiny neurons
Loss of Executive Function (Planning)
Decreased fibre diameter Reduce neural input
Muscle Atrophy - Gait Dysfunction
CORTEX Pyramidal neurons
Loss of Short Term Memory (Dementia)
Fibre type switching
Chorea
Decreased Creatine Kinase (energy stores)
Psychiatric disturbances (delusionsparanoiaanxiety)
Decreased Creatine Kinase (energy stores)
Saccadic eye movements
Loss of Brain Neurotrophic factor BDNF
Depression Mitochondrial dysfunction - energy
Loss of Balance - Vestibular
Huntingtonrsquos disease is not just a disease of the CNS
Peripheral effects of HD
Weight loss
(Adapted from van der Burg (2009) Lancet Neurology 8 765-774
Need to treat all defects using multi-disciplinary intervention
No treatment is
currently available that
slows alters or
reverses the disease
progression
Treatment of Symptoms
Pharmacological Therapies
Antipsychotics
Benzodiazepines
Dopamine Antagonists
Antidepressants
Antichoreic Agents
NEWER MEDICATION
Glutamate Blockers
antioxidants (Q10)
Nerve Growth Factors
Creatine
Stem Cell and
Foetal Tissue Transplants
IMPROVE
NEUROGENESIS
AS THERAPY
Replacing old or lost neurons with new
neurons
NEUROGENESIS
Upregulated by Mental and Physical
Exercise
Physical stimulation (exercise)
upregulates production of endogenous
stem cells within the brain
Cognitive stimulation increases stem cell
survival and integration of new neurons
Together increased production and
survival of neural stem cells in mouse
models of HD
Environmental enrichment - combined
use of mental and physical stimulation to
effect neurological changes
HEROs (Huntingtons Enrichment Rehabilitation Optimisation Scheme)
AIM Implement Environmental Enrichment Program (HEROS)
bullOUTCOMES Slow progression of Huntingtonrsquos disease
bullUpregulate stem cells within the brain and assist their maturation and integration into the existing brain circuitry bullImprove QOL for people with HD benefits carers and families
bullChange policy and practice for treatment of HD
bullMULTIDISCIPLINARY RESEARCH COLLABORATION neuroscientists neurologists neuroradiologists psychologists and psychiatrists occupational therapists physiotherapists exercise physiologists social workers AND the HD Association
Scientifically validate our research Myriad of assessments
Participant Baseline measures Taken June 2010
1 Psychiatric assessment ndash Clinical UHDRS motor score
2 Occupational Therapy and Physiotherapy assessment
3 MRI Brain Volume and fMRI - Functional Imaging and Mapping
4 Blood Biochemical tests ndash Insulin BDNF Creatine Kinase Salivary Cortisol
5 Physical Movement analyses i Height Weight Muscle Dimensions Composition
ii Muscle Strength ndash Isokinetic Isometric Contractions
iii Gait and Walking
iv Fine Motor and Reaction time
v Balance Prevalence of Falls QOL
MRI and fMRI to measure brain volume and function
Body Composition
Height Weight
Arm and Thigh
measurements
Dexa Scan ndash
Dual Energy X-Ray
Absorptiometry scan
ndash Body Composition
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Launch March 2010
Huntingtonrsquos
disease (HD)
Inherited Neurodegenerative
Disorder
Mutation in the Htt gene
50 chance of inheritance if either
parent has the mutated gene
Onset ndash 30-70 years of age
Incidence ~57 per 100000 in
Australia
HD is a fatal complex and
severely debilitating disease
for which there is no cure
There is a gradual loss of neural cells and
muscle cells
So gradual loss of cognitive physical
and emotional function
HISTORY
Paracelsus (1527) 16th century
1872 recognized as a disease for first time
Dr George Huntington (New York) published
ldquoOn Choreardquo in The Medical and Surgical
Reporter of Philadelphia
22 years - Sole publication of just a few paragraphs
was entirely anecdotal and unreferenced
1993 the huntingtin protein was inextricably linked
to the huntingtin gene (Htt or IT15) and to the
disease
HOW
Mutation in the Htt gene
Htt gene has C A G repeat in
exon 1
Normal = 9-36 repeats
Mutant gene = 40 -
250
Produces an abnormal protein
with a polyglutamine tract
Length of CAG repeat
correlates with age of onset
(can be as young as 2)
ABNORMAL PROTEIN -
NEURAL LOSS
protein-protein interactions
With normal proteins
Aggregates in cytoplasm
Inclusion bodies in nucleus
bullVesicular Transport Defective
bullGene transcription and expression
affected
NORMAL PROTEIN In nucleus cell body dendrites of many nerve cells
Transcription vesicle transport cytoskeletal anchoring and pro-survival properties
Timed loss of neurons with abnormal HD protein
RESULT
Loss of neurons in specific brain regions
In the striatum (basal ganglia) causing
loss of movement control
In the cortex and cerebellum - causing
Psychosis and Dementia
Loss of brain volume
Striatal neurons
Coordinate complicated motor and
visual and thinking tasks
- Computer games
- Driving a car
Striatal neurons linked to cortical
neurons
Striatum is also
affected in
Parkinsonrsquos disease
Muscle Movement Disorders - CHOREA hyperkinetic - dystonia and rigidity hypokinetic initiating voluntary movements
Chorea Atrophy
Summary of Symptoms Neural Cell Death
Cognitive (Neural)
Symptoms
Muscle Cell Deficits
Motor (Muscular) Symptoms
STRIATUM Loss GABAergic medium spiny neurons
Loss of Executive Function (Planning)
Decreased fibre diameter Reduce neural input
Muscle Atrophy - Gait Dysfunction
CORTEX Pyramidal neurons
Loss of Short Term Memory (Dementia)
Fibre type switching
Chorea
Decreased Creatine Kinase (energy stores)
Psychiatric disturbances (delusionsparanoiaanxiety)
Decreased Creatine Kinase (energy stores)
Saccadic eye movements
Loss of Brain Neurotrophic factor BDNF
Depression Mitochondrial dysfunction - energy
Loss of Balance - Vestibular
Huntingtonrsquos disease is not just a disease of the CNS
Peripheral effects of HD
Weight loss
(Adapted from van der Burg (2009) Lancet Neurology 8 765-774
Need to treat all defects using multi-disciplinary intervention
No treatment is
currently available that
slows alters or
reverses the disease
progression
Treatment of Symptoms
Pharmacological Therapies
Antipsychotics
Benzodiazepines
Dopamine Antagonists
Antidepressants
Antichoreic Agents
NEWER MEDICATION
Glutamate Blockers
antioxidants (Q10)
Nerve Growth Factors
Creatine
Stem Cell and
Foetal Tissue Transplants
IMPROVE
NEUROGENESIS
AS THERAPY
Replacing old or lost neurons with new
neurons
NEUROGENESIS
Upregulated by Mental and Physical
Exercise
Physical stimulation (exercise)
upregulates production of endogenous
stem cells within the brain
Cognitive stimulation increases stem cell
survival and integration of new neurons
Together increased production and
survival of neural stem cells in mouse
models of HD
Environmental enrichment - combined
use of mental and physical stimulation to
effect neurological changes
HEROs (Huntingtons Enrichment Rehabilitation Optimisation Scheme)
AIM Implement Environmental Enrichment Program (HEROS)
bullOUTCOMES Slow progression of Huntingtonrsquos disease
bullUpregulate stem cells within the brain and assist their maturation and integration into the existing brain circuitry bullImprove QOL for people with HD benefits carers and families
bullChange policy and practice for treatment of HD
bullMULTIDISCIPLINARY RESEARCH COLLABORATION neuroscientists neurologists neuroradiologists psychologists and psychiatrists occupational therapists physiotherapists exercise physiologists social workers AND the HD Association
Scientifically validate our research Myriad of assessments
Participant Baseline measures Taken June 2010
1 Psychiatric assessment ndash Clinical UHDRS motor score
2 Occupational Therapy and Physiotherapy assessment
3 MRI Brain Volume and fMRI - Functional Imaging and Mapping
4 Blood Biochemical tests ndash Insulin BDNF Creatine Kinase Salivary Cortisol
5 Physical Movement analyses i Height Weight Muscle Dimensions Composition
ii Muscle Strength ndash Isokinetic Isometric Contractions
iii Gait and Walking
iv Fine Motor and Reaction time
v Balance Prevalence of Falls QOL
MRI and fMRI to measure brain volume and function
Body Composition
Height Weight
Arm and Thigh
measurements
Dexa Scan ndash
Dual Energy X-Ray
Absorptiometry scan
ndash Body Composition
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Huntingtonrsquos
disease (HD)
Inherited Neurodegenerative
Disorder
Mutation in the Htt gene
50 chance of inheritance if either
parent has the mutated gene
Onset ndash 30-70 years of age
Incidence ~57 per 100000 in
Australia
HD is a fatal complex and
severely debilitating disease
for which there is no cure
There is a gradual loss of neural cells and
muscle cells
So gradual loss of cognitive physical
and emotional function
HISTORY
Paracelsus (1527) 16th century
1872 recognized as a disease for first time
Dr George Huntington (New York) published
ldquoOn Choreardquo in The Medical and Surgical
Reporter of Philadelphia
22 years - Sole publication of just a few paragraphs
was entirely anecdotal and unreferenced
1993 the huntingtin protein was inextricably linked
to the huntingtin gene (Htt or IT15) and to the
disease
HOW
Mutation in the Htt gene
Htt gene has C A G repeat in
exon 1
Normal = 9-36 repeats
Mutant gene = 40 -
250
Produces an abnormal protein
with a polyglutamine tract
Length of CAG repeat
correlates with age of onset
(can be as young as 2)
ABNORMAL PROTEIN -
NEURAL LOSS
protein-protein interactions
With normal proteins
Aggregates in cytoplasm
Inclusion bodies in nucleus
bullVesicular Transport Defective
bullGene transcription and expression
affected
NORMAL PROTEIN In nucleus cell body dendrites of many nerve cells
Transcription vesicle transport cytoskeletal anchoring and pro-survival properties
Timed loss of neurons with abnormal HD protein
RESULT
Loss of neurons in specific brain regions
In the striatum (basal ganglia) causing
loss of movement control
In the cortex and cerebellum - causing
Psychosis and Dementia
Loss of brain volume
Striatal neurons
Coordinate complicated motor and
visual and thinking tasks
- Computer games
- Driving a car
Striatal neurons linked to cortical
neurons
Striatum is also
affected in
Parkinsonrsquos disease
Muscle Movement Disorders - CHOREA hyperkinetic - dystonia and rigidity hypokinetic initiating voluntary movements
Chorea Atrophy
Summary of Symptoms Neural Cell Death
Cognitive (Neural)
Symptoms
Muscle Cell Deficits
Motor (Muscular) Symptoms
STRIATUM Loss GABAergic medium spiny neurons
Loss of Executive Function (Planning)
Decreased fibre diameter Reduce neural input
Muscle Atrophy - Gait Dysfunction
CORTEX Pyramidal neurons
Loss of Short Term Memory (Dementia)
Fibre type switching
Chorea
Decreased Creatine Kinase (energy stores)
Psychiatric disturbances (delusionsparanoiaanxiety)
Decreased Creatine Kinase (energy stores)
Saccadic eye movements
Loss of Brain Neurotrophic factor BDNF
Depression Mitochondrial dysfunction - energy
Loss of Balance - Vestibular
Huntingtonrsquos disease is not just a disease of the CNS
Peripheral effects of HD
Weight loss
(Adapted from van der Burg (2009) Lancet Neurology 8 765-774
Need to treat all defects using multi-disciplinary intervention
No treatment is
currently available that
slows alters or
reverses the disease
progression
Treatment of Symptoms
Pharmacological Therapies
Antipsychotics
Benzodiazepines
Dopamine Antagonists
Antidepressants
Antichoreic Agents
NEWER MEDICATION
Glutamate Blockers
antioxidants (Q10)
Nerve Growth Factors
Creatine
Stem Cell and
Foetal Tissue Transplants
IMPROVE
NEUROGENESIS
AS THERAPY
Replacing old or lost neurons with new
neurons
NEUROGENESIS
Upregulated by Mental and Physical
Exercise
Physical stimulation (exercise)
upregulates production of endogenous
stem cells within the brain
Cognitive stimulation increases stem cell
survival and integration of new neurons
Together increased production and
survival of neural stem cells in mouse
models of HD
Environmental enrichment - combined
use of mental and physical stimulation to
effect neurological changes
HEROs (Huntingtons Enrichment Rehabilitation Optimisation Scheme)
AIM Implement Environmental Enrichment Program (HEROS)
bullOUTCOMES Slow progression of Huntingtonrsquos disease
bullUpregulate stem cells within the brain and assist their maturation and integration into the existing brain circuitry bullImprove QOL for people with HD benefits carers and families
bullChange policy and practice for treatment of HD
bullMULTIDISCIPLINARY RESEARCH COLLABORATION neuroscientists neurologists neuroradiologists psychologists and psychiatrists occupational therapists physiotherapists exercise physiologists social workers AND the HD Association
Scientifically validate our research Myriad of assessments
Participant Baseline measures Taken June 2010
1 Psychiatric assessment ndash Clinical UHDRS motor score
2 Occupational Therapy and Physiotherapy assessment
3 MRI Brain Volume and fMRI - Functional Imaging and Mapping
4 Blood Biochemical tests ndash Insulin BDNF Creatine Kinase Salivary Cortisol
5 Physical Movement analyses i Height Weight Muscle Dimensions Composition
ii Muscle Strength ndash Isokinetic Isometric Contractions
iii Gait and Walking
iv Fine Motor and Reaction time
v Balance Prevalence of Falls QOL
MRI and fMRI to measure brain volume and function
Body Composition
Height Weight
Arm and Thigh
measurements
Dexa Scan ndash
Dual Energy X-Ray
Absorptiometry scan
ndash Body Composition
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
HD is a fatal complex and
severely debilitating disease
for which there is no cure
There is a gradual loss of neural cells and
muscle cells
So gradual loss of cognitive physical
and emotional function
HISTORY
Paracelsus (1527) 16th century
1872 recognized as a disease for first time
Dr George Huntington (New York) published
ldquoOn Choreardquo in The Medical and Surgical
Reporter of Philadelphia
22 years - Sole publication of just a few paragraphs
was entirely anecdotal and unreferenced
1993 the huntingtin protein was inextricably linked
to the huntingtin gene (Htt or IT15) and to the
disease
HOW
Mutation in the Htt gene
Htt gene has C A G repeat in
exon 1
Normal = 9-36 repeats
Mutant gene = 40 -
250
Produces an abnormal protein
with a polyglutamine tract
Length of CAG repeat
correlates with age of onset
(can be as young as 2)
ABNORMAL PROTEIN -
NEURAL LOSS
protein-protein interactions
With normal proteins
Aggregates in cytoplasm
Inclusion bodies in nucleus
bullVesicular Transport Defective
bullGene transcription and expression
affected
NORMAL PROTEIN In nucleus cell body dendrites of many nerve cells
Transcription vesicle transport cytoskeletal anchoring and pro-survival properties
Timed loss of neurons with abnormal HD protein
RESULT
Loss of neurons in specific brain regions
In the striatum (basal ganglia) causing
loss of movement control
In the cortex and cerebellum - causing
Psychosis and Dementia
Loss of brain volume
Striatal neurons
Coordinate complicated motor and
visual and thinking tasks
- Computer games
- Driving a car
Striatal neurons linked to cortical
neurons
Striatum is also
affected in
Parkinsonrsquos disease
Muscle Movement Disorders - CHOREA hyperkinetic - dystonia and rigidity hypokinetic initiating voluntary movements
Chorea Atrophy
Summary of Symptoms Neural Cell Death
Cognitive (Neural)
Symptoms
Muscle Cell Deficits
Motor (Muscular) Symptoms
STRIATUM Loss GABAergic medium spiny neurons
Loss of Executive Function (Planning)
Decreased fibre diameter Reduce neural input
Muscle Atrophy - Gait Dysfunction
CORTEX Pyramidal neurons
Loss of Short Term Memory (Dementia)
Fibre type switching
Chorea
Decreased Creatine Kinase (energy stores)
Psychiatric disturbances (delusionsparanoiaanxiety)
Decreased Creatine Kinase (energy stores)
Saccadic eye movements
Loss of Brain Neurotrophic factor BDNF
Depression Mitochondrial dysfunction - energy
Loss of Balance - Vestibular
Huntingtonrsquos disease is not just a disease of the CNS
Peripheral effects of HD
Weight loss
(Adapted from van der Burg (2009) Lancet Neurology 8 765-774
Need to treat all defects using multi-disciplinary intervention
No treatment is
currently available that
slows alters or
reverses the disease
progression
Treatment of Symptoms
Pharmacological Therapies
Antipsychotics
Benzodiazepines
Dopamine Antagonists
Antidepressants
Antichoreic Agents
NEWER MEDICATION
Glutamate Blockers
antioxidants (Q10)
Nerve Growth Factors
Creatine
Stem Cell and
Foetal Tissue Transplants
IMPROVE
NEUROGENESIS
AS THERAPY
Replacing old or lost neurons with new
neurons
NEUROGENESIS
Upregulated by Mental and Physical
Exercise
Physical stimulation (exercise)
upregulates production of endogenous
stem cells within the brain
Cognitive stimulation increases stem cell
survival and integration of new neurons
Together increased production and
survival of neural stem cells in mouse
models of HD
Environmental enrichment - combined
use of mental and physical stimulation to
effect neurological changes
HEROs (Huntingtons Enrichment Rehabilitation Optimisation Scheme)
AIM Implement Environmental Enrichment Program (HEROS)
bullOUTCOMES Slow progression of Huntingtonrsquos disease
bullUpregulate stem cells within the brain and assist their maturation and integration into the existing brain circuitry bullImprove QOL for people with HD benefits carers and families
bullChange policy and practice for treatment of HD
bullMULTIDISCIPLINARY RESEARCH COLLABORATION neuroscientists neurologists neuroradiologists psychologists and psychiatrists occupational therapists physiotherapists exercise physiologists social workers AND the HD Association
Scientifically validate our research Myriad of assessments
Participant Baseline measures Taken June 2010
1 Psychiatric assessment ndash Clinical UHDRS motor score
2 Occupational Therapy and Physiotherapy assessment
3 MRI Brain Volume and fMRI - Functional Imaging and Mapping
4 Blood Biochemical tests ndash Insulin BDNF Creatine Kinase Salivary Cortisol
5 Physical Movement analyses i Height Weight Muscle Dimensions Composition
ii Muscle Strength ndash Isokinetic Isometric Contractions
iii Gait and Walking
iv Fine Motor and Reaction time
v Balance Prevalence of Falls QOL
MRI and fMRI to measure brain volume and function
Body Composition
Height Weight
Arm and Thigh
measurements
Dexa Scan ndash
Dual Energy X-Ray
Absorptiometry scan
ndash Body Composition
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
HISTORY
Paracelsus (1527) 16th century
1872 recognized as a disease for first time
Dr George Huntington (New York) published
ldquoOn Choreardquo in The Medical and Surgical
Reporter of Philadelphia
22 years - Sole publication of just a few paragraphs
was entirely anecdotal and unreferenced
1993 the huntingtin protein was inextricably linked
to the huntingtin gene (Htt or IT15) and to the
disease
HOW
Mutation in the Htt gene
Htt gene has C A G repeat in
exon 1
Normal = 9-36 repeats
Mutant gene = 40 -
250
Produces an abnormal protein
with a polyglutamine tract
Length of CAG repeat
correlates with age of onset
(can be as young as 2)
ABNORMAL PROTEIN -
NEURAL LOSS
protein-protein interactions
With normal proteins
Aggregates in cytoplasm
Inclusion bodies in nucleus
bullVesicular Transport Defective
bullGene transcription and expression
affected
NORMAL PROTEIN In nucleus cell body dendrites of many nerve cells
Transcription vesicle transport cytoskeletal anchoring and pro-survival properties
Timed loss of neurons with abnormal HD protein
RESULT
Loss of neurons in specific brain regions
In the striatum (basal ganglia) causing
loss of movement control
In the cortex and cerebellum - causing
Psychosis and Dementia
Loss of brain volume
Striatal neurons
Coordinate complicated motor and
visual and thinking tasks
- Computer games
- Driving a car
Striatal neurons linked to cortical
neurons
Striatum is also
affected in
Parkinsonrsquos disease
Muscle Movement Disorders - CHOREA hyperkinetic - dystonia and rigidity hypokinetic initiating voluntary movements
Chorea Atrophy
Summary of Symptoms Neural Cell Death
Cognitive (Neural)
Symptoms
Muscle Cell Deficits
Motor (Muscular) Symptoms
STRIATUM Loss GABAergic medium spiny neurons
Loss of Executive Function (Planning)
Decreased fibre diameter Reduce neural input
Muscle Atrophy - Gait Dysfunction
CORTEX Pyramidal neurons
Loss of Short Term Memory (Dementia)
Fibre type switching
Chorea
Decreased Creatine Kinase (energy stores)
Psychiatric disturbances (delusionsparanoiaanxiety)
Decreased Creatine Kinase (energy stores)
Saccadic eye movements
Loss of Brain Neurotrophic factor BDNF
Depression Mitochondrial dysfunction - energy
Loss of Balance - Vestibular
Huntingtonrsquos disease is not just a disease of the CNS
Peripheral effects of HD
Weight loss
(Adapted from van der Burg (2009) Lancet Neurology 8 765-774
Need to treat all defects using multi-disciplinary intervention
No treatment is
currently available that
slows alters or
reverses the disease
progression
Treatment of Symptoms
Pharmacological Therapies
Antipsychotics
Benzodiazepines
Dopamine Antagonists
Antidepressants
Antichoreic Agents
NEWER MEDICATION
Glutamate Blockers
antioxidants (Q10)
Nerve Growth Factors
Creatine
Stem Cell and
Foetal Tissue Transplants
IMPROVE
NEUROGENESIS
AS THERAPY
Replacing old or lost neurons with new
neurons
NEUROGENESIS
Upregulated by Mental and Physical
Exercise
Physical stimulation (exercise)
upregulates production of endogenous
stem cells within the brain
Cognitive stimulation increases stem cell
survival and integration of new neurons
Together increased production and
survival of neural stem cells in mouse
models of HD
Environmental enrichment - combined
use of mental and physical stimulation to
effect neurological changes
HEROs (Huntingtons Enrichment Rehabilitation Optimisation Scheme)
AIM Implement Environmental Enrichment Program (HEROS)
bullOUTCOMES Slow progression of Huntingtonrsquos disease
bullUpregulate stem cells within the brain and assist their maturation and integration into the existing brain circuitry bullImprove QOL for people with HD benefits carers and families
bullChange policy and practice for treatment of HD
bullMULTIDISCIPLINARY RESEARCH COLLABORATION neuroscientists neurologists neuroradiologists psychologists and psychiatrists occupational therapists physiotherapists exercise physiologists social workers AND the HD Association
Scientifically validate our research Myriad of assessments
Participant Baseline measures Taken June 2010
1 Psychiatric assessment ndash Clinical UHDRS motor score
2 Occupational Therapy and Physiotherapy assessment
3 MRI Brain Volume and fMRI - Functional Imaging and Mapping
4 Blood Biochemical tests ndash Insulin BDNF Creatine Kinase Salivary Cortisol
5 Physical Movement analyses i Height Weight Muscle Dimensions Composition
ii Muscle Strength ndash Isokinetic Isometric Contractions
iii Gait and Walking
iv Fine Motor and Reaction time
v Balance Prevalence of Falls QOL
MRI and fMRI to measure brain volume and function
Body Composition
Height Weight
Arm and Thigh
measurements
Dexa Scan ndash
Dual Energy X-Ray
Absorptiometry scan
ndash Body Composition
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
HOW
Mutation in the Htt gene
Htt gene has C A G repeat in
exon 1
Normal = 9-36 repeats
Mutant gene = 40 -
250
Produces an abnormal protein
with a polyglutamine tract
Length of CAG repeat
correlates with age of onset
(can be as young as 2)
ABNORMAL PROTEIN -
NEURAL LOSS
protein-protein interactions
With normal proteins
Aggregates in cytoplasm
Inclusion bodies in nucleus
bullVesicular Transport Defective
bullGene transcription and expression
affected
NORMAL PROTEIN In nucleus cell body dendrites of many nerve cells
Transcription vesicle transport cytoskeletal anchoring and pro-survival properties
Timed loss of neurons with abnormal HD protein
RESULT
Loss of neurons in specific brain regions
In the striatum (basal ganglia) causing
loss of movement control
In the cortex and cerebellum - causing
Psychosis and Dementia
Loss of brain volume
Striatal neurons
Coordinate complicated motor and
visual and thinking tasks
- Computer games
- Driving a car
Striatal neurons linked to cortical
neurons
Striatum is also
affected in
Parkinsonrsquos disease
Muscle Movement Disorders - CHOREA hyperkinetic - dystonia and rigidity hypokinetic initiating voluntary movements
Chorea Atrophy
Summary of Symptoms Neural Cell Death
Cognitive (Neural)
Symptoms
Muscle Cell Deficits
Motor (Muscular) Symptoms
STRIATUM Loss GABAergic medium spiny neurons
Loss of Executive Function (Planning)
Decreased fibre diameter Reduce neural input
Muscle Atrophy - Gait Dysfunction
CORTEX Pyramidal neurons
Loss of Short Term Memory (Dementia)
Fibre type switching
Chorea
Decreased Creatine Kinase (energy stores)
Psychiatric disturbances (delusionsparanoiaanxiety)
Decreased Creatine Kinase (energy stores)
Saccadic eye movements
Loss of Brain Neurotrophic factor BDNF
Depression Mitochondrial dysfunction - energy
Loss of Balance - Vestibular
Huntingtonrsquos disease is not just a disease of the CNS
Peripheral effects of HD
Weight loss
(Adapted from van der Burg (2009) Lancet Neurology 8 765-774
Need to treat all defects using multi-disciplinary intervention
No treatment is
currently available that
slows alters or
reverses the disease
progression
Treatment of Symptoms
Pharmacological Therapies
Antipsychotics
Benzodiazepines
Dopamine Antagonists
Antidepressants
Antichoreic Agents
NEWER MEDICATION
Glutamate Blockers
antioxidants (Q10)
Nerve Growth Factors
Creatine
Stem Cell and
Foetal Tissue Transplants
IMPROVE
NEUROGENESIS
AS THERAPY
Replacing old or lost neurons with new
neurons
NEUROGENESIS
Upregulated by Mental and Physical
Exercise
Physical stimulation (exercise)
upregulates production of endogenous
stem cells within the brain
Cognitive stimulation increases stem cell
survival and integration of new neurons
Together increased production and
survival of neural stem cells in mouse
models of HD
Environmental enrichment - combined
use of mental and physical stimulation to
effect neurological changes
HEROs (Huntingtons Enrichment Rehabilitation Optimisation Scheme)
AIM Implement Environmental Enrichment Program (HEROS)
bullOUTCOMES Slow progression of Huntingtonrsquos disease
bullUpregulate stem cells within the brain and assist their maturation and integration into the existing brain circuitry bullImprove QOL for people with HD benefits carers and families
bullChange policy and practice for treatment of HD
bullMULTIDISCIPLINARY RESEARCH COLLABORATION neuroscientists neurologists neuroradiologists psychologists and psychiatrists occupational therapists physiotherapists exercise physiologists social workers AND the HD Association
Scientifically validate our research Myriad of assessments
Participant Baseline measures Taken June 2010
1 Psychiatric assessment ndash Clinical UHDRS motor score
2 Occupational Therapy and Physiotherapy assessment
3 MRI Brain Volume and fMRI - Functional Imaging and Mapping
4 Blood Biochemical tests ndash Insulin BDNF Creatine Kinase Salivary Cortisol
5 Physical Movement analyses i Height Weight Muscle Dimensions Composition
ii Muscle Strength ndash Isokinetic Isometric Contractions
iii Gait and Walking
iv Fine Motor and Reaction time
v Balance Prevalence of Falls QOL
MRI and fMRI to measure brain volume and function
Body Composition
Height Weight
Arm and Thigh
measurements
Dexa Scan ndash
Dual Energy X-Ray
Absorptiometry scan
ndash Body Composition
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
ABNORMAL PROTEIN -
NEURAL LOSS
protein-protein interactions
With normal proteins
Aggregates in cytoplasm
Inclusion bodies in nucleus
bullVesicular Transport Defective
bullGene transcription and expression
affected
NORMAL PROTEIN In nucleus cell body dendrites of many nerve cells
Transcription vesicle transport cytoskeletal anchoring and pro-survival properties
Timed loss of neurons with abnormal HD protein
RESULT
Loss of neurons in specific brain regions
In the striatum (basal ganglia) causing
loss of movement control
In the cortex and cerebellum - causing
Psychosis and Dementia
Loss of brain volume
Striatal neurons
Coordinate complicated motor and
visual and thinking tasks
- Computer games
- Driving a car
Striatal neurons linked to cortical
neurons
Striatum is also
affected in
Parkinsonrsquos disease
Muscle Movement Disorders - CHOREA hyperkinetic - dystonia and rigidity hypokinetic initiating voluntary movements
Chorea Atrophy
Summary of Symptoms Neural Cell Death
Cognitive (Neural)
Symptoms
Muscle Cell Deficits
Motor (Muscular) Symptoms
STRIATUM Loss GABAergic medium spiny neurons
Loss of Executive Function (Planning)
Decreased fibre diameter Reduce neural input
Muscle Atrophy - Gait Dysfunction
CORTEX Pyramidal neurons
Loss of Short Term Memory (Dementia)
Fibre type switching
Chorea
Decreased Creatine Kinase (energy stores)
Psychiatric disturbances (delusionsparanoiaanxiety)
Decreased Creatine Kinase (energy stores)
Saccadic eye movements
Loss of Brain Neurotrophic factor BDNF
Depression Mitochondrial dysfunction - energy
Loss of Balance - Vestibular
Huntingtonrsquos disease is not just a disease of the CNS
Peripheral effects of HD
Weight loss
(Adapted from van der Burg (2009) Lancet Neurology 8 765-774
Need to treat all defects using multi-disciplinary intervention
No treatment is
currently available that
slows alters or
reverses the disease
progression
Treatment of Symptoms
Pharmacological Therapies
Antipsychotics
Benzodiazepines
Dopamine Antagonists
Antidepressants
Antichoreic Agents
NEWER MEDICATION
Glutamate Blockers
antioxidants (Q10)
Nerve Growth Factors
Creatine
Stem Cell and
Foetal Tissue Transplants
IMPROVE
NEUROGENESIS
AS THERAPY
Replacing old or lost neurons with new
neurons
NEUROGENESIS
Upregulated by Mental and Physical
Exercise
Physical stimulation (exercise)
upregulates production of endogenous
stem cells within the brain
Cognitive stimulation increases stem cell
survival and integration of new neurons
Together increased production and
survival of neural stem cells in mouse
models of HD
Environmental enrichment - combined
use of mental and physical stimulation to
effect neurological changes
HEROs (Huntingtons Enrichment Rehabilitation Optimisation Scheme)
AIM Implement Environmental Enrichment Program (HEROS)
bullOUTCOMES Slow progression of Huntingtonrsquos disease
bullUpregulate stem cells within the brain and assist their maturation and integration into the existing brain circuitry bullImprove QOL for people with HD benefits carers and families
bullChange policy and practice for treatment of HD
bullMULTIDISCIPLINARY RESEARCH COLLABORATION neuroscientists neurologists neuroradiologists psychologists and psychiatrists occupational therapists physiotherapists exercise physiologists social workers AND the HD Association
Scientifically validate our research Myriad of assessments
Participant Baseline measures Taken June 2010
1 Psychiatric assessment ndash Clinical UHDRS motor score
2 Occupational Therapy and Physiotherapy assessment
3 MRI Brain Volume and fMRI - Functional Imaging and Mapping
4 Blood Biochemical tests ndash Insulin BDNF Creatine Kinase Salivary Cortisol
5 Physical Movement analyses i Height Weight Muscle Dimensions Composition
ii Muscle Strength ndash Isokinetic Isometric Contractions
iii Gait and Walking
iv Fine Motor and Reaction time
v Balance Prevalence of Falls QOL
MRI and fMRI to measure brain volume and function
Body Composition
Height Weight
Arm and Thigh
measurements
Dexa Scan ndash
Dual Energy X-Ray
Absorptiometry scan
ndash Body Composition
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Timed loss of neurons with abnormal HD protein
RESULT
Loss of neurons in specific brain regions
In the striatum (basal ganglia) causing
loss of movement control
In the cortex and cerebellum - causing
Psychosis and Dementia
Loss of brain volume
Striatal neurons
Coordinate complicated motor and
visual and thinking tasks
- Computer games
- Driving a car
Striatal neurons linked to cortical
neurons
Striatum is also
affected in
Parkinsonrsquos disease
Muscle Movement Disorders - CHOREA hyperkinetic - dystonia and rigidity hypokinetic initiating voluntary movements
Chorea Atrophy
Summary of Symptoms Neural Cell Death
Cognitive (Neural)
Symptoms
Muscle Cell Deficits
Motor (Muscular) Symptoms
STRIATUM Loss GABAergic medium spiny neurons
Loss of Executive Function (Planning)
Decreased fibre diameter Reduce neural input
Muscle Atrophy - Gait Dysfunction
CORTEX Pyramidal neurons
Loss of Short Term Memory (Dementia)
Fibre type switching
Chorea
Decreased Creatine Kinase (energy stores)
Psychiatric disturbances (delusionsparanoiaanxiety)
Decreased Creatine Kinase (energy stores)
Saccadic eye movements
Loss of Brain Neurotrophic factor BDNF
Depression Mitochondrial dysfunction - energy
Loss of Balance - Vestibular
Huntingtonrsquos disease is not just a disease of the CNS
Peripheral effects of HD
Weight loss
(Adapted from van der Burg (2009) Lancet Neurology 8 765-774
Need to treat all defects using multi-disciplinary intervention
No treatment is
currently available that
slows alters or
reverses the disease
progression
Treatment of Symptoms
Pharmacological Therapies
Antipsychotics
Benzodiazepines
Dopamine Antagonists
Antidepressants
Antichoreic Agents
NEWER MEDICATION
Glutamate Blockers
antioxidants (Q10)
Nerve Growth Factors
Creatine
Stem Cell and
Foetal Tissue Transplants
IMPROVE
NEUROGENESIS
AS THERAPY
Replacing old or lost neurons with new
neurons
NEUROGENESIS
Upregulated by Mental and Physical
Exercise
Physical stimulation (exercise)
upregulates production of endogenous
stem cells within the brain
Cognitive stimulation increases stem cell
survival and integration of new neurons
Together increased production and
survival of neural stem cells in mouse
models of HD
Environmental enrichment - combined
use of mental and physical stimulation to
effect neurological changes
HEROs (Huntingtons Enrichment Rehabilitation Optimisation Scheme)
AIM Implement Environmental Enrichment Program (HEROS)
bullOUTCOMES Slow progression of Huntingtonrsquos disease
bullUpregulate stem cells within the brain and assist their maturation and integration into the existing brain circuitry bullImprove QOL for people with HD benefits carers and families
bullChange policy and practice for treatment of HD
bullMULTIDISCIPLINARY RESEARCH COLLABORATION neuroscientists neurologists neuroradiologists psychologists and psychiatrists occupational therapists physiotherapists exercise physiologists social workers AND the HD Association
Scientifically validate our research Myriad of assessments
Participant Baseline measures Taken June 2010
1 Psychiatric assessment ndash Clinical UHDRS motor score
2 Occupational Therapy and Physiotherapy assessment
3 MRI Brain Volume and fMRI - Functional Imaging and Mapping
4 Blood Biochemical tests ndash Insulin BDNF Creatine Kinase Salivary Cortisol
5 Physical Movement analyses i Height Weight Muscle Dimensions Composition
ii Muscle Strength ndash Isokinetic Isometric Contractions
iii Gait and Walking
iv Fine Motor and Reaction time
v Balance Prevalence of Falls QOL
MRI and fMRI to measure brain volume and function
Body Composition
Height Weight
Arm and Thigh
measurements
Dexa Scan ndash
Dual Energy X-Ray
Absorptiometry scan
ndash Body Composition
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
RESULT
Loss of neurons in specific brain regions
In the striatum (basal ganglia) causing
loss of movement control
In the cortex and cerebellum - causing
Psychosis and Dementia
Loss of brain volume
Striatal neurons
Coordinate complicated motor and
visual and thinking tasks
- Computer games
- Driving a car
Striatal neurons linked to cortical
neurons
Striatum is also
affected in
Parkinsonrsquos disease
Muscle Movement Disorders - CHOREA hyperkinetic - dystonia and rigidity hypokinetic initiating voluntary movements
Chorea Atrophy
Summary of Symptoms Neural Cell Death
Cognitive (Neural)
Symptoms
Muscle Cell Deficits
Motor (Muscular) Symptoms
STRIATUM Loss GABAergic medium spiny neurons
Loss of Executive Function (Planning)
Decreased fibre diameter Reduce neural input
Muscle Atrophy - Gait Dysfunction
CORTEX Pyramidal neurons
Loss of Short Term Memory (Dementia)
Fibre type switching
Chorea
Decreased Creatine Kinase (energy stores)
Psychiatric disturbances (delusionsparanoiaanxiety)
Decreased Creatine Kinase (energy stores)
Saccadic eye movements
Loss of Brain Neurotrophic factor BDNF
Depression Mitochondrial dysfunction - energy
Loss of Balance - Vestibular
Huntingtonrsquos disease is not just a disease of the CNS
Peripheral effects of HD
Weight loss
(Adapted from van der Burg (2009) Lancet Neurology 8 765-774
Need to treat all defects using multi-disciplinary intervention
No treatment is
currently available that
slows alters or
reverses the disease
progression
Treatment of Symptoms
Pharmacological Therapies
Antipsychotics
Benzodiazepines
Dopamine Antagonists
Antidepressants
Antichoreic Agents
NEWER MEDICATION
Glutamate Blockers
antioxidants (Q10)
Nerve Growth Factors
Creatine
Stem Cell and
Foetal Tissue Transplants
IMPROVE
NEUROGENESIS
AS THERAPY
Replacing old or lost neurons with new
neurons
NEUROGENESIS
Upregulated by Mental and Physical
Exercise
Physical stimulation (exercise)
upregulates production of endogenous
stem cells within the brain
Cognitive stimulation increases stem cell
survival and integration of new neurons
Together increased production and
survival of neural stem cells in mouse
models of HD
Environmental enrichment - combined
use of mental and physical stimulation to
effect neurological changes
HEROs (Huntingtons Enrichment Rehabilitation Optimisation Scheme)
AIM Implement Environmental Enrichment Program (HEROS)
bullOUTCOMES Slow progression of Huntingtonrsquos disease
bullUpregulate stem cells within the brain and assist their maturation and integration into the existing brain circuitry bullImprove QOL for people with HD benefits carers and families
bullChange policy and practice for treatment of HD
bullMULTIDISCIPLINARY RESEARCH COLLABORATION neuroscientists neurologists neuroradiologists psychologists and psychiatrists occupational therapists physiotherapists exercise physiologists social workers AND the HD Association
Scientifically validate our research Myriad of assessments
Participant Baseline measures Taken June 2010
1 Psychiatric assessment ndash Clinical UHDRS motor score
2 Occupational Therapy and Physiotherapy assessment
3 MRI Brain Volume and fMRI - Functional Imaging and Mapping
4 Blood Biochemical tests ndash Insulin BDNF Creatine Kinase Salivary Cortisol
5 Physical Movement analyses i Height Weight Muscle Dimensions Composition
ii Muscle Strength ndash Isokinetic Isometric Contractions
iii Gait and Walking
iv Fine Motor and Reaction time
v Balance Prevalence of Falls QOL
MRI and fMRI to measure brain volume and function
Body Composition
Height Weight
Arm and Thigh
measurements
Dexa Scan ndash
Dual Energy X-Ray
Absorptiometry scan
ndash Body Composition
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Striatal neurons
Coordinate complicated motor and
visual and thinking tasks
- Computer games
- Driving a car
Striatal neurons linked to cortical
neurons
Striatum is also
affected in
Parkinsonrsquos disease
Muscle Movement Disorders - CHOREA hyperkinetic - dystonia and rigidity hypokinetic initiating voluntary movements
Chorea Atrophy
Summary of Symptoms Neural Cell Death
Cognitive (Neural)
Symptoms
Muscle Cell Deficits
Motor (Muscular) Symptoms
STRIATUM Loss GABAergic medium spiny neurons
Loss of Executive Function (Planning)
Decreased fibre diameter Reduce neural input
Muscle Atrophy - Gait Dysfunction
CORTEX Pyramidal neurons
Loss of Short Term Memory (Dementia)
Fibre type switching
Chorea
Decreased Creatine Kinase (energy stores)
Psychiatric disturbances (delusionsparanoiaanxiety)
Decreased Creatine Kinase (energy stores)
Saccadic eye movements
Loss of Brain Neurotrophic factor BDNF
Depression Mitochondrial dysfunction - energy
Loss of Balance - Vestibular
Huntingtonrsquos disease is not just a disease of the CNS
Peripheral effects of HD
Weight loss
(Adapted from van der Burg (2009) Lancet Neurology 8 765-774
Need to treat all defects using multi-disciplinary intervention
No treatment is
currently available that
slows alters or
reverses the disease
progression
Treatment of Symptoms
Pharmacological Therapies
Antipsychotics
Benzodiazepines
Dopamine Antagonists
Antidepressants
Antichoreic Agents
NEWER MEDICATION
Glutamate Blockers
antioxidants (Q10)
Nerve Growth Factors
Creatine
Stem Cell and
Foetal Tissue Transplants
IMPROVE
NEUROGENESIS
AS THERAPY
Replacing old or lost neurons with new
neurons
NEUROGENESIS
Upregulated by Mental and Physical
Exercise
Physical stimulation (exercise)
upregulates production of endogenous
stem cells within the brain
Cognitive stimulation increases stem cell
survival and integration of new neurons
Together increased production and
survival of neural stem cells in mouse
models of HD
Environmental enrichment - combined
use of mental and physical stimulation to
effect neurological changes
HEROs (Huntingtons Enrichment Rehabilitation Optimisation Scheme)
AIM Implement Environmental Enrichment Program (HEROS)
bullOUTCOMES Slow progression of Huntingtonrsquos disease
bullUpregulate stem cells within the brain and assist their maturation and integration into the existing brain circuitry bullImprove QOL for people with HD benefits carers and families
bullChange policy and practice for treatment of HD
bullMULTIDISCIPLINARY RESEARCH COLLABORATION neuroscientists neurologists neuroradiologists psychologists and psychiatrists occupational therapists physiotherapists exercise physiologists social workers AND the HD Association
Scientifically validate our research Myriad of assessments
Participant Baseline measures Taken June 2010
1 Psychiatric assessment ndash Clinical UHDRS motor score
2 Occupational Therapy and Physiotherapy assessment
3 MRI Brain Volume and fMRI - Functional Imaging and Mapping
4 Blood Biochemical tests ndash Insulin BDNF Creatine Kinase Salivary Cortisol
5 Physical Movement analyses i Height Weight Muscle Dimensions Composition
ii Muscle Strength ndash Isokinetic Isometric Contractions
iii Gait and Walking
iv Fine Motor and Reaction time
v Balance Prevalence of Falls QOL
MRI and fMRI to measure brain volume and function
Body Composition
Height Weight
Arm and Thigh
measurements
Dexa Scan ndash
Dual Energy X-Ray
Absorptiometry scan
ndash Body Composition
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Muscle Movement Disorders - CHOREA hyperkinetic - dystonia and rigidity hypokinetic initiating voluntary movements
Chorea Atrophy
Summary of Symptoms Neural Cell Death
Cognitive (Neural)
Symptoms
Muscle Cell Deficits
Motor (Muscular) Symptoms
STRIATUM Loss GABAergic medium spiny neurons
Loss of Executive Function (Planning)
Decreased fibre diameter Reduce neural input
Muscle Atrophy - Gait Dysfunction
CORTEX Pyramidal neurons
Loss of Short Term Memory (Dementia)
Fibre type switching
Chorea
Decreased Creatine Kinase (energy stores)
Psychiatric disturbances (delusionsparanoiaanxiety)
Decreased Creatine Kinase (energy stores)
Saccadic eye movements
Loss of Brain Neurotrophic factor BDNF
Depression Mitochondrial dysfunction - energy
Loss of Balance - Vestibular
Huntingtonrsquos disease is not just a disease of the CNS
Peripheral effects of HD
Weight loss
(Adapted from van der Burg (2009) Lancet Neurology 8 765-774
Need to treat all defects using multi-disciplinary intervention
No treatment is
currently available that
slows alters or
reverses the disease
progression
Treatment of Symptoms
Pharmacological Therapies
Antipsychotics
Benzodiazepines
Dopamine Antagonists
Antidepressants
Antichoreic Agents
NEWER MEDICATION
Glutamate Blockers
antioxidants (Q10)
Nerve Growth Factors
Creatine
Stem Cell and
Foetal Tissue Transplants
IMPROVE
NEUROGENESIS
AS THERAPY
Replacing old or lost neurons with new
neurons
NEUROGENESIS
Upregulated by Mental and Physical
Exercise
Physical stimulation (exercise)
upregulates production of endogenous
stem cells within the brain
Cognitive stimulation increases stem cell
survival and integration of new neurons
Together increased production and
survival of neural stem cells in mouse
models of HD
Environmental enrichment - combined
use of mental and physical stimulation to
effect neurological changes
HEROs (Huntingtons Enrichment Rehabilitation Optimisation Scheme)
AIM Implement Environmental Enrichment Program (HEROS)
bullOUTCOMES Slow progression of Huntingtonrsquos disease
bullUpregulate stem cells within the brain and assist their maturation and integration into the existing brain circuitry bullImprove QOL for people with HD benefits carers and families
bullChange policy and practice for treatment of HD
bullMULTIDISCIPLINARY RESEARCH COLLABORATION neuroscientists neurologists neuroradiologists psychologists and psychiatrists occupational therapists physiotherapists exercise physiologists social workers AND the HD Association
Scientifically validate our research Myriad of assessments
Participant Baseline measures Taken June 2010
1 Psychiatric assessment ndash Clinical UHDRS motor score
2 Occupational Therapy and Physiotherapy assessment
3 MRI Brain Volume and fMRI - Functional Imaging and Mapping
4 Blood Biochemical tests ndash Insulin BDNF Creatine Kinase Salivary Cortisol
5 Physical Movement analyses i Height Weight Muscle Dimensions Composition
ii Muscle Strength ndash Isokinetic Isometric Contractions
iii Gait and Walking
iv Fine Motor and Reaction time
v Balance Prevalence of Falls QOL
MRI and fMRI to measure brain volume and function
Body Composition
Height Weight
Arm and Thigh
measurements
Dexa Scan ndash
Dual Energy X-Ray
Absorptiometry scan
ndash Body Composition
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Summary of Symptoms Neural Cell Death
Cognitive (Neural)
Symptoms
Muscle Cell Deficits
Motor (Muscular) Symptoms
STRIATUM Loss GABAergic medium spiny neurons
Loss of Executive Function (Planning)
Decreased fibre diameter Reduce neural input
Muscle Atrophy - Gait Dysfunction
CORTEX Pyramidal neurons
Loss of Short Term Memory (Dementia)
Fibre type switching
Chorea
Decreased Creatine Kinase (energy stores)
Psychiatric disturbances (delusionsparanoiaanxiety)
Decreased Creatine Kinase (energy stores)
Saccadic eye movements
Loss of Brain Neurotrophic factor BDNF
Depression Mitochondrial dysfunction - energy
Loss of Balance - Vestibular
Huntingtonrsquos disease is not just a disease of the CNS
Peripheral effects of HD
Weight loss
(Adapted from van der Burg (2009) Lancet Neurology 8 765-774
Need to treat all defects using multi-disciplinary intervention
No treatment is
currently available that
slows alters or
reverses the disease
progression
Treatment of Symptoms
Pharmacological Therapies
Antipsychotics
Benzodiazepines
Dopamine Antagonists
Antidepressants
Antichoreic Agents
NEWER MEDICATION
Glutamate Blockers
antioxidants (Q10)
Nerve Growth Factors
Creatine
Stem Cell and
Foetal Tissue Transplants
IMPROVE
NEUROGENESIS
AS THERAPY
Replacing old or lost neurons with new
neurons
NEUROGENESIS
Upregulated by Mental and Physical
Exercise
Physical stimulation (exercise)
upregulates production of endogenous
stem cells within the brain
Cognitive stimulation increases stem cell
survival and integration of new neurons
Together increased production and
survival of neural stem cells in mouse
models of HD
Environmental enrichment - combined
use of mental and physical stimulation to
effect neurological changes
HEROs (Huntingtons Enrichment Rehabilitation Optimisation Scheme)
AIM Implement Environmental Enrichment Program (HEROS)
bullOUTCOMES Slow progression of Huntingtonrsquos disease
bullUpregulate stem cells within the brain and assist their maturation and integration into the existing brain circuitry bullImprove QOL for people with HD benefits carers and families
bullChange policy and practice for treatment of HD
bullMULTIDISCIPLINARY RESEARCH COLLABORATION neuroscientists neurologists neuroradiologists psychologists and psychiatrists occupational therapists physiotherapists exercise physiologists social workers AND the HD Association
Scientifically validate our research Myriad of assessments
Participant Baseline measures Taken June 2010
1 Psychiatric assessment ndash Clinical UHDRS motor score
2 Occupational Therapy and Physiotherapy assessment
3 MRI Brain Volume and fMRI - Functional Imaging and Mapping
4 Blood Biochemical tests ndash Insulin BDNF Creatine Kinase Salivary Cortisol
5 Physical Movement analyses i Height Weight Muscle Dimensions Composition
ii Muscle Strength ndash Isokinetic Isometric Contractions
iii Gait and Walking
iv Fine Motor and Reaction time
v Balance Prevalence of Falls QOL
MRI and fMRI to measure brain volume and function
Body Composition
Height Weight
Arm and Thigh
measurements
Dexa Scan ndash
Dual Energy X-Ray
Absorptiometry scan
ndash Body Composition
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Huntingtonrsquos disease is not just a disease of the CNS
Peripheral effects of HD
Weight loss
(Adapted from van der Burg (2009) Lancet Neurology 8 765-774
Need to treat all defects using multi-disciplinary intervention
No treatment is
currently available that
slows alters or
reverses the disease
progression
Treatment of Symptoms
Pharmacological Therapies
Antipsychotics
Benzodiazepines
Dopamine Antagonists
Antidepressants
Antichoreic Agents
NEWER MEDICATION
Glutamate Blockers
antioxidants (Q10)
Nerve Growth Factors
Creatine
Stem Cell and
Foetal Tissue Transplants
IMPROVE
NEUROGENESIS
AS THERAPY
Replacing old or lost neurons with new
neurons
NEUROGENESIS
Upregulated by Mental and Physical
Exercise
Physical stimulation (exercise)
upregulates production of endogenous
stem cells within the brain
Cognitive stimulation increases stem cell
survival and integration of new neurons
Together increased production and
survival of neural stem cells in mouse
models of HD
Environmental enrichment - combined
use of mental and physical stimulation to
effect neurological changes
HEROs (Huntingtons Enrichment Rehabilitation Optimisation Scheme)
AIM Implement Environmental Enrichment Program (HEROS)
bullOUTCOMES Slow progression of Huntingtonrsquos disease
bullUpregulate stem cells within the brain and assist their maturation and integration into the existing brain circuitry bullImprove QOL for people with HD benefits carers and families
bullChange policy and practice for treatment of HD
bullMULTIDISCIPLINARY RESEARCH COLLABORATION neuroscientists neurologists neuroradiologists psychologists and psychiatrists occupational therapists physiotherapists exercise physiologists social workers AND the HD Association
Scientifically validate our research Myriad of assessments
Participant Baseline measures Taken June 2010
1 Psychiatric assessment ndash Clinical UHDRS motor score
2 Occupational Therapy and Physiotherapy assessment
3 MRI Brain Volume and fMRI - Functional Imaging and Mapping
4 Blood Biochemical tests ndash Insulin BDNF Creatine Kinase Salivary Cortisol
5 Physical Movement analyses i Height Weight Muscle Dimensions Composition
ii Muscle Strength ndash Isokinetic Isometric Contractions
iii Gait and Walking
iv Fine Motor and Reaction time
v Balance Prevalence of Falls QOL
MRI and fMRI to measure brain volume and function
Body Composition
Height Weight
Arm and Thigh
measurements
Dexa Scan ndash
Dual Energy X-Ray
Absorptiometry scan
ndash Body Composition
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
No treatment is
currently available that
slows alters or
reverses the disease
progression
Treatment of Symptoms
Pharmacological Therapies
Antipsychotics
Benzodiazepines
Dopamine Antagonists
Antidepressants
Antichoreic Agents
NEWER MEDICATION
Glutamate Blockers
antioxidants (Q10)
Nerve Growth Factors
Creatine
Stem Cell and
Foetal Tissue Transplants
IMPROVE
NEUROGENESIS
AS THERAPY
Replacing old or lost neurons with new
neurons
NEUROGENESIS
Upregulated by Mental and Physical
Exercise
Physical stimulation (exercise)
upregulates production of endogenous
stem cells within the brain
Cognitive stimulation increases stem cell
survival and integration of new neurons
Together increased production and
survival of neural stem cells in mouse
models of HD
Environmental enrichment - combined
use of mental and physical stimulation to
effect neurological changes
HEROs (Huntingtons Enrichment Rehabilitation Optimisation Scheme)
AIM Implement Environmental Enrichment Program (HEROS)
bullOUTCOMES Slow progression of Huntingtonrsquos disease
bullUpregulate stem cells within the brain and assist their maturation and integration into the existing brain circuitry bullImprove QOL for people with HD benefits carers and families
bullChange policy and practice for treatment of HD
bullMULTIDISCIPLINARY RESEARCH COLLABORATION neuroscientists neurologists neuroradiologists psychologists and psychiatrists occupational therapists physiotherapists exercise physiologists social workers AND the HD Association
Scientifically validate our research Myriad of assessments
Participant Baseline measures Taken June 2010
1 Psychiatric assessment ndash Clinical UHDRS motor score
2 Occupational Therapy and Physiotherapy assessment
3 MRI Brain Volume and fMRI - Functional Imaging and Mapping
4 Blood Biochemical tests ndash Insulin BDNF Creatine Kinase Salivary Cortisol
5 Physical Movement analyses i Height Weight Muscle Dimensions Composition
ii Muscle Strength ndash Isokinetic Isometric Contractions
iii Gait and Walking
iv Fine Motor and Reaction time
v Balance Prevalence of Falls QOL
MRI and fMRI to measure brain volume and function
Body Composition
Height Weight
Arm and Thigh
measurements
Dexa Scan ndash
Dual Energy X-Ray
Absorptiometry scan
ndash Body Composition
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Treatment of Symptoms
Pharmacological Therapies
Antipsychotics
Benzodiazepines
Dopamine Antagonists
Antidepressants
Antichoreic Agents
NEWER MEDICATION
Glutamate Blockers
antioxidants (Q10)
Nerve Growth Factors
Creatine
Stem Cell and
Foetal Tissue Transplants
IMPROVE
NEUROGENESIS
AS THERAPY
Replacing old or lost neurons with new
neurons
NEUROGENESIS
Upregulated by Mental and Physical
Exercise
Physical stimulation (exercise)
upregulates production of endogenous
stem cells within the brain
Cognitive stimulation increases stem cell
survival and integration of new neurons
Together increased production and
survival of neural stem cells in mouse
models of HD
Environmental enrichment - combined
use of mental and physical stimulation to
effect neurological changes
HEROs (Huntingtons Enrichment Rehabilitation Optimisation Scheme)
AIM Implement Environmental Enrichment Program (HEROS)
bullOUTCOMES Slow progression of Huntingtonrsquos disease
bullUpregulate stem cells within the brain and assist their maturation and integration into the existing brain circuitry bullImprove QOL for people with HD benefits carers and families
bullChange policy and practice for treatment of HD
bullMULTIDISCIPLINARY RESEARCH COLLABORATION neuroscientists neurologists neuroradiologists psychologists and psychiatrists occupational therapists physiotherapists exercise physiologists social workers AND the HD Association
Scientifically validate our research Myriad of assessments
Participant Baseline measures Taken June 2010
1 Psychiatric assessment ndash Clinical UHDRS motor score
2 Occupational Therapy and Physiotherapy assessment
3 MRI Brain Volume and fMRI - Functional Imaging and Mapping
4 Blood Biochemical tests ndash Insulin BDNF Creatine Kinase Salivary Cortisol
5 Physical Movement analyses i Height Weight Muscle Dimensions Composition
ii Muscle Strength ndash Isokinetic Isometric Contractions
iii Gait and Walking
iv Fine Motor and Reaction time
v Balance Prevalence of Falls QOL
MRI and fMRI to measure brain volume and function
Body Composition
Height Weight
Arm and Thigh
measurements
Dexa Scan ndash
Dual Energy X-Ray
Absorptiometry scan
ndash Body Composition
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
IMPROVE
NEUROGENESIS
AS THERAPY
Replacing old or lost neurons with new
neurons
NEUROGENESIS
Upregulated by Mental and Physical
Exercise
Physical stimulation (exercise)
upregulates production of endogenous
stem cells within the brain
Cognitive stimulation increases stem cell
survival and integration of new neurons
Together increased production and
survival of neural stem cells in mouse
models of HD
Environmental enrichment - combined
use of mental and physical stimulation to
effect neurological changes
HEROs (Huntingtons Enrichment Rehabilitation Optimisation Scheme)
AIM Implement Environmental Enrichment Program (HEROS)
bullOUTCOMES Slow progression of Huntingtonrsquos disease
bullUpregulate stem cells within the brain and assist their maturation and integration into the existing brain circuitry bullImprove QOL for people with HD benefits carers and families
bullChange policy and practice for treatment of HD
bullMULTIDISCIPLINARY RESEARCH COLLABORATION neuroscientists neurologists neuroradiologists psychologists and psychiatrists occupational therapists physiotherapists exercise physiologists social workers AND the HD Association
Scientifically validate our research Myriad of assessments
Participant Baseline measures Taken June 2010
1 Psychiatric assessment ndash Clinical UHDRS motor score
2 Occupational Therapy and Physiotherapy assessment
3 MRI Brain Volume and fMRI - Functional Imaging and Mapping
4 Blood Biochemical tests ndash Insulin BDNF Creatine Kinase Salivary Cortisol
5 Physical Movement analyses i Height Weight Muscle Dimensions Composition
ii Muscle Strength ndash Isokinetic Isometric Contractions
iii Gait and Walking
iv Fine Motor and Reaction time
v Balance Prevalence of Falls QOL
MRI and fMRI to measure brain volume and function
Body Composition
Height Weight
Arm and Thigh
measurements
Dexa Scan ndash
Dual Energy X-Ray
Absorptiometry scan
ndash Body Composition
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
NEUROGENESIS
Upregulated by Mental and Physical
Exercise
Physical stimulation (exercise)
upregulates production of endogenous
stem cells within the brain
Cognitive stimulation increases stem cell
survival and integration of new neurons
Together increased production and
survival of neural stem cells in mouse
models of HD
Environmental enrichment - combined
use of mental and physical stimulation to
effect neurological changes
HEROs (Huntingtons Enrichment Rehabilitation Optimisation Scheme)
AIM Implement Environmental Enrichment Program (HEROS)
bullOUTCOMES Slow progression of Huntingtonrsquos disease
bullUpregulate stem cells within the brain and assist their maturation and integration into the existing brain circuitry bullImprove QOL for people with HD benefits carers and families
bullChange policy and practice for treatment of HD
bullMULTIDISCIPLINARY RESEARCH COLLABORATION neuroscientists neurologists neuroradiologists psychologists and psychiatrists occupational therapists physiotherapists exercise physiologists social workers AND the HD Association
Scientifically validate our research Myriad of assessments
Participant Baseline measures Taken June 2010
1 Psychiatric assessment ndash Clinical UHDRS motor score
2 Occupational Therapy and Physiotherapy assessment
3 MRI Brain Volume and fMRI - Functional Imaging and Mapping
4 Blood Biochemical tests ndash Insulin BDNF Creatine Kinase Salivary Cortisol
5 Physical Movement analyses i Height Weight Muscle Dimensions Composition
ii Muscle Strength ndash Isokinetic Isometric Contractions
iii Gait and Walking
iv Fine Motor and Reaction time
v Balance Prevalence of Falls QOL
MRI and fMRI to measure brain volume and function
Body Composition
Height Weight
Arm and Thigh
measurements
Dexa Scan ndash
Dual Energy X-Ray
Absorptiometry scan
ndash Body Composition
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
HEROs (Huntingtons Enrichment Rehabilitation Optimisation Scheme)
AIM Implement Environmental Enrichment Program (HEROS)
bullOUTCOMES Slow progression of Huntingtonrsquos disease
bullUpregulate stem cells within the brain and assist their maturation and integration into the existing brain circuitry bullImprove QOL for people with HD benefits carers and families
bullChange policy and practice for treatment of HD
bullMULTIDISCIPLINARY RESEARCH COLLABORATION neuroscientists neurologists neuroradiologists psychologists and psychiatrists occupational therapists physiotherapists exercise physiologists social workers AND the HD Association
Scientifically validate our research Myriad of assessments
Participant Baseline measures Taken June 2010
1 Psychiatric assessment ndash Clinical UHDRS motor score
2 Occupational Therapy and Physiotherapy assessment
3 MRI Brain Volume and fMRI - Functional Imaging and Mapping
4 Blood Biochemical tests ndash Insulin BDNF Creatine Kinase Salivary Cortisol
5 Physical Movement analyses i Height Weight Muscle Dimensions Composition
ii Muscle Strength ndash Isokinetic Isometric Contractions
iii Gait and Walking
iv Fine Motor and Reaction time
v Balance Prevalence of Falls QOL
MRI and fMRI to measure brain volume and function
Body Composition
Height Weight
Arm and Thigh
measurements
Dexa Scan ndash
Dual Energy X-Ray
Absorptiometry scan
ndash Body Composition
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Scientifically validate our research Myriad of assessments
Participant Baseline measures Taken June 2010
1 Psychiatric assessment ndash Clinical UHDRS motor score
2 Occupational Therapy and Physiotherapy assessment
3 MRI Brain Volume and fMRI - Functional Imaging and Mapping
4 Blood Biochemical tests ndash Insulin BDNF Creatine Kinase Salivary Cortisol
5 Physical Movement analyses i Height Weight Muscle Dimensions Composition
ii Muscle Strength ndash Isokinetic Isometric Contractions
iii Gait and Walking
iv Fine Motor and Reaction time
v Balance Prevalence of Falls QOL
MRI and fMRI to measure brain volume and function
Body Composition
Height Weight
Arm and Thigh
measurements
Dexa Scan ndash
Dual Energy X-Ray
Absorptiometry scan
ndash Body Composition
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
MRI and fMRI to measure brain volume and function
Body Composition
Height Weight
Arm and Thigh
measurements
Dexa Scan ndash
Dual Energy X-Ray
Absorptiometry scan
ndash Body Composition
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Body Composition
Height Weight
Arm and Thigh
measurements
Dexa Scan ndash
Dual Energy X-Ray
Absorptiometry scan
ndash Body Composition
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Neurocom Balance
Visual Somatosensory
and Vestibular Control
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Isokinetic and Isometric
Measurements
Muscle Force
Hand Grip Strength
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Analysis of Gait
Walking Stride Length
and Stride Frequency
Video Analysis of Muscle
and Joint Movement
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Force Plate
Measurements of
Walking Stride and
Gait
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Fine Motor Control
Reaction Time Testing
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
COGNITIVE TESTING PROCEDURES
Clinical neuropsychological tests
bullBecks Depression Inventory
bullHopkins Verbal Learning Test
bullDKEFS trail making trial
bullSymbol Digit Modalities test
bullDKEFS Stroop Test
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Environmental Enrichment
TREATMENT
Mental physical and social stimulation
ldquoUse it or you lose itrdquo
ndash ldquoa passive lifestyle may contribute to the earlier onset of symptomsrdquo
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Neuroscientists Neurologist
Neuropsychiatrist
Neuropsychologist
Neuroradiologist
Exercise physiologists
(biomechanics muscle force
gross and fine motor training)
Physiotherapists
Cognitive
Motor
Occupational Therapist
(cognitive stimulation) Social
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Intervention
(Group B = 9)
Intervention
Non-Intervention
CONTROL GROUP
(Group A = 10)
Intermediate Measurements
Final Measurements
Long-term
Intervention
STUDY DESIGN ndash RANDOMISED CONTROLLED
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
1 Clinical gym exercises ndash 1 hour per week
2 Home-based exercises - daily
3 Occupational therapy
ndash targeted deficits detected at baseline by psychologists
ndash 1 hour per fortnight
High compliance rates were experienced
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
OUTCOME MEASURED at 9 Mths and 18 Mths
MOTOR FUNCTION - Clinical Unified Huntingtonrsquos Disease Rating Scale (UHDRS)
BRAIN IMAGING - MRI fMRI (executive and motor function) DTI
PHYSICALPHYSIOLOGICAL FACTORS
DEXA muscle strength Neurocom Balance
COGNITION
Symbol Digit Modalities Test Hopkins Verbal Learning Test-Revised DKEFS Colour
Word Interference Test DKEFS Trail Making Trials
DEPRESSION - Beck Depression Inventory-II
QUALITY OF LIFE OUTCOMES
Short Form 36v2 Health Survey HD Quality of Life Battery for Carers
STATISTICS
Between groups analysis - Independent t-test on difference between values (summed data)
Within groups analysis - Repeated measures ANOVAKruskall-Wallis Test (within groups)
plt005 was considered statistically significant
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Highly significant rate of motor deterioration during the control period
The intervention significantly reduced the rate of motor deterioration
Maintained baseline levels after 18 months
CLINICAL MEASURE
Unified Huntingtonrsquos Disease Rating Scale ndash Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score
p=0311 p=0020
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Fat Difference
Control
Intervention 1
Intervention 2
-5000
-4000
-3000
-2000
-1000
0
1000
2000
3000
L Arm R Arm Trunk L Leg R Leg Head Total
Lean Difference
Control
Intervention 1
Intervention 2
OVERALL RESULTS
REDUCED loss of fat and lean mass
Significantly increased lean mass over 18 months
in contrast to significant loss in controls which is characteristic of the disease
BODY COMPOSITION
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Muscle Strength
Major Muscle Groups
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
Mean Difference plusmnSEM
(plt00001)
Chest Press Lat Pull Down
Seated Row
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Muscle Strength
Major Muscle Groups
Beneficial physical changes ndash impacts independent functioning
Leg Press
Leg Extension Leg Flexion
SIGNIFICANT GAINS IN STRENGTH
AFTER 9 AND 18 MONTHS OF
INTERVENTION
(plt00001)
Mean Difference plusmnSEM
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
-2000
-1500
-1000
-500
000
500
1000
1500
2000
2500
1 2 3 4 5 6 Comp
Ch
an
ge
in
Me
an
Eq
uil
ibri
um
Sco
re (
)
Conditions
Sensory Organisation Test
Control Intervention 1 Intervention 2
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus Apparatus consists of a support surface (forceplates) and a 3-sided visual surround moved independently
A higher score denotes better postural stability (where 100 = no sway0 = fall)
Mean Difference plusmnSEM
SIGNIFICANT IMPROVEMENT IN BALANCE
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Cognitive Changes
Timepoint (n)
Difference in values Within Groups (p)
Control (10)
9 mths (13)
18 mths (10)
Group A Group B
C 9mths 9mths 18mths
Total Recall (n) 060 plusmn115 -125 plusmn083 186 plusmn147 0535 0992 0056 0142
Delayed Recall (n) -10 plusmn052 03 plusmn042 143 plusmn115 0032 0291 0890 0095
Retention () -1975 plusmn100 148 plusmn52 2293 plusmn102 0017 0629 0634 0035
Recognition
Discrimination
Index (score)
10 plusmn068 -095 plusmn053 071 plusmn052 0274 0137 0086 0094
Significant Trend
Hopkins Verbal Learning Test - MemoryLearning
Values = Mean plusmnSEM Within Group ndash Repeated Measures ANOVA Between Groups ndash Independent T-test on difference
Significant deterioration in controls
Maintained baseline levels after 9 MONTHS
Significant improvement after 18 MONTHS
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
DEPRESSION
-8
-6
-4
-2
0
2
4
6
Control Int 1 Int 2Ch
an
ge
in
Sco
re r
ela
tiv
e t
o b
ase
lin
e
Beck Depression Inventory
M
Mean Difference plusmnSEM
p=00886
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Brain Imaging
Performed at Neuroradiology Sir Charles Gairdner Hospital
Mike Bynevelt (Head of Dept) Neuroradiologist
MRI - Structure
Whole brain volumetric analysis ndash WM vs GM
fMRI - Function
BOLD response during performance of an executive function task
(Simon Interference task)
DTI ndash Integitry
Diffusion Tensor Imaging to assess changes to FA and MD to
assess changes to white and grey matter in response to the
intervention
RESULTS STILL TO COME
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Multidisciplinary rehabilitation intervention in early-mid stage HD patients appears
to slow symptoms of disease progression
Patients with early-mid stage Huntingtonrsquos disease can participate in continuous multidisciplinary
rehabilitation as an adjunct to pharmaceutical therapy without adverse effects
Participants demonstrated high levels of compliance
Participants exhibited cognitivephysicalfunctional benefits - encouraging given the small
sample size
JA Thompson TM Cruickshank LE Penailillo JW Lee RU Newton RA Barker MR Ziman
(2013) The effects of multidisciplinary rehabilitation in patients with early-to-middle-stage
Huntingtons disease a pilot study Eur J Neurol 2012 Dec 7 doi 101111ene12053 [Epub ahead
of print]
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Acknowledgments
Thank you to the patients families and carers
for their participation in this research project
The generous assistance of the gyms is
gratefully acknowledged
ECU Vario Health amp Wellness Institute
ECU Sport amp Fitness Centre
South Lakes Leisure Centre
Lords Fitness Centre
Positive Fit
We thank the many assessors and students
who assisted with data collection
This project was supported by Lotterywest
and ECU
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Characteristic
Group A
(mean z-score
[range])
Group B
(mean z-score
[range])
Cognitive
Assessment
(mean z-score)
0034 [-05 to 08] 0063 [-06 to 05]
Motor Assessment
(mean z-score) -016 [-13 to 084] -013 [-17 to 10]
Characteristic Group A
(mean plusmnSEM)
Group B
(mean plusmnSEM)
Number of
participants 10 9
Gender MF 64 45
Age (years) 508 plusmn 25 537 plusmn 29
Age at Diagnosis
(years) 495 plusmn 28 482 plusmn 22
Disease Duration
(years) 26 plusmn 08 43 plusmn 12
CAG Number 441 plusmn 06 431 plusmn 11
CAG Index 4279 plusmn 222 3991 plusmn 537
Body Mass Index
(kgm2) 270 plusmn 14 264 plusmn 14
Participants were assigned to two groups equally matched for
cognitive and motor scores at baseline
Groups were assessed for differences in baseline demographics ndash no statistically significant
differences were detected
Groups were randomly assigned to either receive the intervention or not
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Domain Range of Score
1 Ocular pursuit 0 - 4
2 Saccade initiation 0 - 4
3 Saccade velocity 0 - 4
4 Dysarthria 0 - 4
5 Tongue protrusion 0 - 4
6 Finger taps 0 - 4
7 PronateSupinate hands 0 - 4
8 Luria 0 - 4
9 Rigidity-Arms 0 - 4
10 Bradykinesia-Body 0 - 4
11 Maximal dystonia 0 - 4
12 Maximal chorea 0 - 4
13 Gait 0 - 4
14 Tandem walking 0 - 4
15 Retropulsion pull test 0 - 4
16 Weight actual weight
17 Diagnosis confidence
level 0 - 4
Total Sum of scores
Highly significant rate of motor deterioration during the control period (p=0003)
The intervention significantly reduced the rate of motor deterioration (p=0020) which was
maintained at lower levels after intervention 2 (p=0311)
Unified Huntingtonrsquos Disease Rating Scale ndash Total Motor Score
0
2
4
6
8
10
12
14
16
18
20
Control I 1 I 2
Dif
fere
nce
in
Me
an
UH
DR
S S
core
UHDRS Total Motor Score Difference in Mean Score
p=0311 p=0020
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (10)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
UHDRS 154 plusmn29 56 plusmn16 42 plusmn41
000
3 0178 0038 0345 0028 0020 0311
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Timepoi
nt (n)
Difference in values Within Groups (p) Between
Groups (p)
Control (10)
Interv 1 (20)
Interv 2 (7)
Group A Group B Ctl v
Int 1
Int 2
v Int 1 C I 1 I 1 I 2 18mths
Fat Mass
(kg) -19 plusmn07 06 plusmn04 -01 plusmn11 0013
049
6 0365 0880 0497 0002 0529
Lean
Mass
(kg)
-10 plusmn05 03 plusmn04 08 plusmn08 006
7
039
8 0102 0230 0013 0112 0596
BMD
(gcm3) 00 plusmn00 00 plusmn00 00 plusmn00 0430 0128 0567 0686 0907 0675 0679
Lean+B
MC (kg) -10 plusmn06 03 plusmn04 08 plusmn08
005
8
039
8 0094 0232 0012 0097 0592
Total
Mass
(kg)
-29 plusmn11 10 plusmn07 07 plusmn18 0013 099
3 0161 0600 0081 0006 0875
BMI
(kgm2) -060 plusmn03 003 plusmn03 009 plusmn06
006
4 0144 0208 0829 0178 0184 0914
Body Composition
FAT MASS Significant loss of fat mass during control period (p=0013)
Maintained fat mass during intervention period (pgt005)
Highly significant difference between control + intervention groups (p=0002)
LEAN MASS A trend towards significant loss of lean mass during control period (p=0067)
No significant loss during intervention period ndash non-significant gain
After longitudinal intervention significant overall increase detected (p=0013)
TOTAL BODY MASS Significant loss of total body mass during control period (p=0013)
After longitudinal intervention a trend towards a significant increase in
body mass detected (predominantly +lean mass 0081)
Highly significant difference between control + intervention groups (p=0006)
Significant Trend
Note Maintenance of body composition during second round
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
Control Int 1 Int 2
-6
-7 4
-14
-11
-6
6 0
-12 7
-20
-9 9
2 -2
0 -28
-5 13
-16 -6
-10
5 5
-16 -2
0 0
-19 1
1 -16
-7 -21
6
-12 22
Deteriorated
Improved
Maintained levels (plusmn2)
No Test
Two sample test of proportion
Timepoint Deteriorated Maintained
Improved p
Control Period 700 300 (0-9) 0128 (9-18) 0163 (0-18) 0046
Intervention 1 500 500
Intervention 2 286 714
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
-1000
-800
-600
-400
-200
000
200
400
600
Control Int 1 Int 2
NeuroCom Balance Test Difference in composite mean
score
Group A Group B Combined
0001000200030004000500060007000
0 1 2 3
Me
an
Sco
re
NeuroCom Composite SOT Equilibrium Scores
Group A
Group B
p=0109 (27)
Sensory Organisation Test
NeuroCom SMART Balance Master Apparatus
p=0041 (38)
Mean Difference
plusmnSEM
Error Bars =
SEM
No Intervention + Intervention
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function
Timepoint (n)
Difference in values Within Group (p) Between Groups (p)
Control (10)
Interv 1 (13)
Interv 2 (11)
Group A Group B Ctl v Int 1 Int 2 v Int 1
C I 1 I 1 I 2 18mths
D-KEFS Colour Word Interference Test ndash (number performed)
Colour naming 58 plusmn29 44 plusmn25 44 plusmn37 0133 0137 0309 0218 0039 0750 0997
Non-significant improvement after intervention 1
with a further improvement after intervention 2 and significant difference from baseline (p=0039)
Word Reading 07 plusmn17 18 plusmn16 514 plusmn187 0883 0080 0746 0011 0019 0655 0249
Maintained during control period with improvement after intervention 1
and significant improvement after intervention 2 (p=0011) and overall from baseline (p=0019)
Inhibition (eg green) -18 plusmn41 31 plusmn48 1283 plusmn68 0853 0338 1000 0150 0150 0521 0291
Maintained during control period and after intervention 1
Non-significant improvement after intervention 2
D-KEFS Trail Making Trials ndash (time taken)
Visual Scanning 62 plusmn39 41 plusmn33 -56 plusmn76 0064 0748 0150 0535 0467 0703 0187
A trend for significant deterioration after control period Non-significant deterioration after intervention 1
Non-significant improvement after intervention 2
Number Sequencing -07 plusmn42 117 plusmn43 -107 plusmn46 0659 0057 0035 0008 0351 0076 0008
Maintained after control period Borderlinesignificant deterioration after intervention 1
Highly significant improvement after intervention 2 (p=0008)
Letter Sequencing -141 plusmn99 99 plusmn43 -49 plusmn53 0054 0076 0587 0407 0732 0015 0066
Borderline significant improvement after control period Significant deterioration after intervention 1
A trend for significant improvement after intervention 2 (p=0066)
Number-Letter Switching
-178 plusmn170 03 plusmn81 188 plusmn73 0487 0665 0373 0012 0036 0296 0380
Non-significant improvement after control period Non-significant improvement after intervention 1
Significant deterioration after intervention 2 (p=0036)
Motor Speed -85 plusmn65 20 plusmn60 -80 plusmn72 0479 0736 0170 0156 0854 0284 0371
Cognitive Changes Significant Trend Executive Function