Teaming Up: Application to Lewy Body DiseasesRicahrd Camicioli, MDCM, FRCP(C)Geriatric Cognitive and Movement DisordersUniversity of Alberta

Disclosures

No relevant disclosure

Limitations to Clinical Studies

Applied to selective populations Males Whites Higher SES Higher education

Focus on specific entities that can be recruited for Alzheimer disease Clinical characteristics may differ based on setting

Geriatric psychiatry, Neurology, Geriatrics, Cognitive Clinic

Excluding populations of interest Older, frail Ignore health/comorbidities

CCNA At a Glance

Who will be recruited where?

• Memory Clinics: SCI, MCI, v‐MCI, AD, Mixed• Stroke Clinics: v‐MCI, Mixed• Movement Disorder Clinics: LBD, PDD, PD‐MCI, PD• Behavioural Neurology Clinics: FTD, PSP, CBD• Competitive Recruitment• No clinic excluded from recruiting a specific Dxcategory.

2016/05/31

Choice of Inclusion and Exclusion criteria

• Broadly inclusive criteria will produce heterogeneous groups that cover the entire dementia population.

• Include almost all co-morbidities and mixed dementias

• Difficult to specify definitions of “pure” disease

MCI

SCI

AD

LBD

FTD

VCI

Mixed

Braak, H. et al. Neurology 2008;70:1916-1925

Lewy Body Pathology in Parkinson’s Disease/Dementia with Lewy Bodies

LewyNet: Nottingham

Mixed Pathology Contributes to Clinical Course

Brenowitz WD 2017

Figure 2 Mild cognitive impairment subtypes and progression to clinically probable Alzheimer disease (A) and probable dementia with Lewy bodies (B).

Tanis J. Ferman et al. Neurology 2013;81:2032-2038

© 2013 American Academy of Neurology

Figure 1 Competing risks: AD and DLBSurvival curves for transitions from amnestic and nonamnestic MCI to DLB and clinically probable AD. AD = Alzheimer disease; DLB = dementia with Lewy bodies; MCI = mild cognitive impairment.

Tanis J. Ferman et al. Neurology 2013;81:2032-2038

© 2013 American Academy of Neurology

Abnormal Gait and Dementia

0102030405060708090

100

PDD VaD DLB PD AD Ctl

Percent

Allan LM, JAGS 2005

Gait Assessment

Standardize Walking PD

Standardized Gait DLB

Multi-Centre Gait Study in PD(Bin Hu, PI)

University of Calgary Observational intervention

University of Alberta Examination of cognitive impact of training

University of Lethbridge Effects of gait training on balance and Aging

University of British Columbia Magnetic resonance imaging changes with exercise

The Effects of Contingency-based Musical Gait Feedback

on Cognition in Individuals with Parkinson’s Disease: Overview

12 weeks; 30 independently mobile persons with mild to moderate PD

Intervention: Semi-randomized (sequential alternating enrollment) into groups Contingency Only – 12 weeks of gait training where

music play was contingent on achieving a set step size Music/Contingency – 6 weeks of passive music listening,

where music played continuously regardless of step size, followed by 6 weeks of contingency-based training

“Dose”: Minimum of 3 walks a week for at least 15 minutes using the musical feedback gait device

Single Blinded Assessments: Baseline, 6 weeks, 12 weeks

The Effects of Contingency-based Musical Gait Feedback

on Cognition in Individuals with Parkinson’s Disease: Measures

CLINICAL BATTERYHoehn and Yahr Stage Assessment

(HY)UPDRS Part III: Motor ExaminationSchwab and England Activities of

Daily LivingModified Cumulative Illness Rating

Scale (MCIRS)AD8 Dementia Screening Interview

Activities of Daily Living (ADLs)Geriatric Depression Scale – Short

Form (GDS)Beck Anxiety Inventory (BAI)

10 Meter Walking – Single and Dual Task

COGNITIVE BATTERYMini Mental State Exam (MMSE)Montreal Cognitive Assessment

(MoCA)Hopkins Verbal Learning Test

(HVLT)Stroop Color-Word Test

Trail Making Tests A & BAttention Network Test (ANT)

Digit Order Test (DOT)

The Effects of Contingency-based Musical Gait Feedback

on Cognition in Individuals with Parkinson’s Disease: Baseline Group Results

Group 1 (n=15); Group 2 (n=15)

No significant differences between groups at baseline Age Independence (Schwab & England) ADLs Cumulative illness rating (MCIRS) Physical activity (LAPAQ) Verbal intellectual ability (NART)

High physical and cognitive functioning

Contingency Only

Music / Contingency

Var Med InterquartRange Med Interquart

Range P

Age 67 12 63 14 0.09

SchEng 80 10 80 10 0.81

AD8 2 3 2 3 0.74ADLs 0 2 0 2 0.86

MCIRS 20 6 23 4 0.59Total PA 805 502 1435 820 0.14

NART 110.8 10.32 116.08 12.56 0.12

INTERIM ANALYSIS*

Contingency Only Music/Contingency

All Weeks

Weeks 1-6 (Training)

Weeks 7-12

(Training)

All WeeksWeeks 1-

6 (Passive)

Weeks 7-12(Training)

Average Distance

(km)1.79 1.79 1.80 2.35 2.34 2.36

Average Duration

(min.)26.35 26.10 26.72 34.13 35.65 32.60

Average Speed

(m/sec)1.08 1.09 1.06 1.16 1.10 1.22

Average Cadence

(steps/min.)108.2 107.7 108.8 112.0 110.3 113.7

Average Step Size (m) 0.60 0.60 0.59 0.63 0.60 0.65

The Effects of Contingency-based Musical Gait Feedback on Cognition in Individuals with

Parkinson’s Disease: Clinical/Cognitive Results of Intervention

Significant Time Effects: MMSE (p=0.0002) Geriatric Depression Scale

(p=0.006) Beck Anxiety Inventory

(p=0.0317) Digit Ordering (p=0.0382)

Significant Group Effects: UPDRS (p=0.0366)

Clinical Significance?

Multi-Centre Gait Assessment: UC, UBC, UA

Chomiak T et al, under review

Michael J Fox Collaboration

Aimed at identifying gaps is PD research related to gait

Anat Mirelman, Quincy Almeida, Teresa Ellis, Chris Hass, Elisa Pelosin, Paolo Bonato, Richard Camicioli, Jamie Hamilton (MJFF)

Lead to synthesis of the literature

CCNA supported analysis of brain areas affected in relation to gait (MMO CCNA Gait Team Lead)

amygdalahippocampussubthalamic nucleus

primary motor

pre-motorSMA

cerebellum

cingulate cortex

corpus callosum

cuneus / pre-cuneus

caudatenucleus accumbensputamen

thalamusinferior parietal lobe

globus pallidus

substantia nigra

PPNcerebellar peduncles

Figure : Regions that been associated with gait dysfunction in Parkinson’s Disease. (a) coronal, (b) sagittal, and (c) transverse views are shown. (d) shows three transverse slices of the brain stem. We have focussed on regions where there are volumetric alterations and/or changes in white matter integrity. The highlighted areas include regions that have exhibited significant differences in comparisons between FOG(+) and FOG(-) participants (studies with or without controls), comparisons between motor subtypes, or show significant correlations with clinical gait measures.

Conclusions Teams can solve gaps in disease knowledge and patient

care

Key is participation and cooperation

Links to primary care and real world setting are critical Goal is personalized medicine

Data collection tools and data management remain works in progress, but are evolving rapidly

Data analysis is complex but tools are becoming available to synthesize diverse and rich data types