modulation of beta-amyloid-related cognitive decline by brain-derived neurotrophic factor val66met...

2
MIS. Results: For detection of aMCI, the MISD had higher sensitivity(0.82 vs 0.55), and NVP (0.88 vs 0.75) when compared with the MIS. Specificity (0.85 vs 0.90),PPV (0.80 vs 0.80), did not differ significantly. The area under the ROC curve for the MISD was 0.91, compared with 0.79 for the MIS. Conclusions: The MISD had a better predictive mode for detecting aMCI in this large sample of elderly people. The MISD could have advantages as a MCI screen for use in the primary care. P2-245 COGNITIVE CONSEQUENCES OF HIGH BETA- AMYLOID LEVELS IN PEOPLE WITH MILD COGNITIVE IMPAIRMENTAND HEALTHY OLDERADULTS: IMPLICATIONS FOR EARLY DETECTION OF ALZHEIMER’S DISEASE Yen Ying Lim 1 , Kathryn Ellis 2 , Karra Harrington 3 , Adrian Kamer 4 , Robb Pietrzak 5 , Ashley Bush 6 , David Darby 6 , Ralph Martins 7 , Colin Masters 6 , Christopher Rowe 6 , Greg Savage 8 , Cassandra Szoeke 9 , Victor Villemagne 10 , David Ames 11 , Paul Maruff 12 , 1 University of Melbourne, Parkville, Australia; 2 St Georges Hospital, Kew, Australia; 3 The Mental Health Research Institute of Victoria, Parkville, Australia; 4 Mental Health Research Institute, Parkville, VIC, Australia; 5 Yale University School of Medicine, New Haven, Connecticut, United States; 6 Mental Health Research Institute of Victoria, Parkville, Australia; 7 Edith Cowan University, Perth, Australia; 8 Macquarie University, Sydney, NSW, Australia; 9 National Ageing Research Institute Inc. (NARI), Melbourne, Australia; 10 Austin Health, Melbourne, Australia; 11 National Ageing Research Institute Inc. (NARI), Parkville, Australia; 12 CogState Ltd, Melbourne, Australia. Contact e-mail: [email protected] Background: Recent studies have suggested that only adults with mild cognitive impairment (MCI) and high Ab amyloid is indicative of incipi- ent Alzheimer’s disease (AD), while adults with MCI and low Ab amyloid may reflect the presence of other neurodegenerative or psychiatric pro- cesses. We aimed to determine the extent to which high Ab amyloid influ- enced cognitive function in healthy older adults and adults with MCI when considered cross-sectionally. Methods: Healthy older adults (n ¼ 178) and adults with MCI (n ¼ 56) enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, underwent positron emission tomography (PET) neuroimaging using Pittsburgh Compound B (PiB) for Ab amyloid, and completed an extensive neuropsychological battery, assessing the cog- nitive domains of verbal and visual episodic memory, executive function, visuoconstruction, attention and processing speed, and language at base- line. Results: No differences were observed between healthy older adults with high and low Ab amyloid. Adults with MCI and low Ab amyloid per- formed worse than MCI with high Ab amyloid on measures of executive function, attention, visuoconstruction, and language. When compared to healthy older adults with low Ab amyloid, both MCI groups with high and low Ab amyloid showed large impairments in episodic memory. How- ever, only the MCI low Ab amyloid group performed worse than healthy older adults with high Ab amyloid on measures of executive function, at- tention, visuoconstruction, and language. Conclusions: Adults with MCI and high Ab amyloid presented with large impairments that were re- stricted to episodic memory, while the episodic memory impairments in MCI with low Ab amyloid were accompanied by additional impairments in executive function, attention, visuoconstruction, and language. This lends support to the hypothesis that MCI with high Ab amyloid reflects the prodromal stage of AD, while MCI with low Ab amyloid may reflect other causes of cognitive impairment. P2-246 DISORIENTATION IN AMNESTIC MILD COGNITIVE IMPAIRMENT IS CORRELATED WITH HYPOMETABOLISM IN THE POSTERIOR CINGULATE So Moon, Ajou University, School of Medicine, Suwon, South Korea. Contact e-mail: [email protected] Background: A lesional study showed that three patients with right retro- splenial lesions had intact performance in the part A of the card-placing test (CPT) but impaired performance in the part B of the CPT. It was insisted that the part A of the CPT assesses egocentric disorientation whereas part B examines heading disorientation. However, the test has not yet been used in any larger population. In addition, neural substrates of the test have not yet been replicated in other studies. In our study, using statistical parametric mapping (SPM) analysis we aimed to investigate anatomical correlates of both part A and B of the CPT in FDG-PET studies of patients with amnestic mild cognitive impairment (aMCI). Methods: A total of 15 aMCI patients were enrolled into the study. Patients underwent standardized neuropsycho- logical tests and part A and part B of the CPT. The CPT scores and K-MMSE scores of 29 cognitively normal people were used for comparison. FDG- PET was performed in the same patients. We used the SPM correlation anal- ysis to extract the regions whose changes in regional cerebral metabolism correlated significantly with part A and B of the CPT with adjustment of age and sex of patients. Results: Controlling for age, sex, and education years, the K-MMSE score and CPT B score was significantly lower in the aMCI group (26.062.0 vs. 28.261.4, p<0.001, and 16.364.4 vs. 19.763.7, p¼0.011). However, CPTA scores did not significantly differ be- tween the two groups (25.563.5 vs. 27.762.7, p¼0.055). The SPM analysis showed that decrease in scores of part A correlated with hypometabolism in bilateral precuneus, posterior cingulate gyri, right crus cerebelli, cerebellar vermis, right anterior and middle cingulate gyri, right superior and middle frontal gyri, left inferior parietal region, and the left angular gyrus. (uncor- rected p<0.05). Decrease in scores of part B correlated with hypometabo- lism in bilateral precuneus, middle and posterior cingulate gyri (uncorrected p<0.005). Conclusions: The test scores of part B of the card placing test correlated well with hypometabolism of the posterior cingulate gyrus and its surrounding areas whereas part A correlated with hypometab- olism in more various areas. P2-247 MODULATION OF BETA-AMYLOID-RELATED COGNITIVE DECLINE BY BRAIN-DERIVED NEUROTROPHIC FACTOR VAL66MET POLYMORPHISM IN PRECLINICAL ALZHEIMER’S DISEASE Yen Ying Lim 1 , Victor Villemagne 2 , Simon Laws 3 , David Ames 4 , Robb Pietrzak 5 , Kathryn Ellis 6 , Karra Harrington 7 , Pierrick Bourgeat 8 , Olivier Salvado 8 , David Darby 6 , Peter Snyder 9 , Ashley Bush 10 , Poster Presentations: P2 P446

Upload: paul

Post on 01-Jan-2017

213 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: Modulation of beta-amyloid-related cognitive decline by brain-derived neurotrophic factor Val66Met polymorphism in preclinical Alzheimer's disease

Poster Presentations: P2P446

MIS.Results: For detection of aMCI, the MISD had higher sensitivity(0.82

vs 0.55), and NVP (0.88 vs 0.75) when compared with the MIS. Specificity

(0.85 vs 0.90),PPV (0.80 vs 0.80), did not differ significantly. The area under

the ROC curve for the MISD was 0.91, compared with 0.79 for the MIS.

Conclusions: The MISD had a better predictive mode for detecting aMCI

in this large sample of elderly people. The MISD could have advantages

as a MCI screen for use in the primary care.

P2-245 COGNITIVE CONSEQUENCES OF HIGH BETA-

AMYLOID LEVELS IN PEOPLE WITH MILD

COGNITIVE IMPAIRMENTAND HEALTHY

OLDER ADULTS: IMPLICATIONS FOR EARLY

DETECTION OFALZHEIMER’S DISEASE

Yen Ying Lim1, Kathryn Ellis2, Karra Harrington3, Adrian Kamer4,

Robb Pietrzak5, Ashley Bush6, David Darby6, Ralph Martins7,

Colin Masters6, Christopher Rowe6, Greg Savage8, Cassandra Szoeke9,

Victor Villemagne10, David Ames11, Paul Maruff12, 1University of

Melbourne, Parkville, Australia; 2St Georges Hospital, Kew, Australia; 3The

Mental Health Research Institute of Victoria, Parkville, Australia; 4Mental

Health Research Institute, Parkville, VIC, Australia; 5Yale University

School of Medicine, New Haven, Connecticut, United States; 6Mental

Health Research Institute of Victoria, Parkville, Australia; 7Edith Cowan

University, Perth, Australia; 8Macquarie University, Sydney, NSW,

Australia; 9National Ageing Research Institute Inc. (NARI), Melbourne,

Australia; 10Austin Health, Melbourne, Australia; 11National Ageing

Research Institute Inc. (NARI), Parkville, Australia; 12CogState Ltd,

Melbourne, Australia. Contact e-mail: [email protected]

Background: Recent studies have suggested that only adults with mild

cognitive impairment (MCI) and high Ab amyloid is indicative of incipi-

ent Alzheimer’s disease (AD), while adults with MCI and low Ab amyloid

may reflect the presence of other neurodegenerative or psychiatric pro-

cesses. We aimed to determine the extent to which high Ab amyloid influ-

enced cognitive function in healthy older adults and adults with MCI when

considered cross-sectionally. Methods:Healthy older adults (n ¼ 178) and

adults with MCI (n ¼ 56) enrolled in the Australian Imaging, Biomarkers

and Lifestyle (AIBL) study, underwent positron emission tomography

(PET) neuroimaging using Pittsburgh Compound B (PiB) for Ab amyloid,

and completed an extensive neuropsychological battery, assessing the cog-

nitive domains of verbal and visual episodic memory, executive function,

visuoconstruction, attention and processing speed, and language at base-

line. Results: No differences were observed between healthy older adults

with high and low Ab amyloid. Adults with MCI and low Ab amyloid per-

formed worse than MCI with high Ab amyloid on measures of executive

function, attention, visuoconstruction, and language. When compared to

healthy older adults with low Ab amyloid, both MCI groups with high

and low Ab amyloid showed large impairments in episodic memory. How-

ever, only the MCI low Ab amyloid group performed worse than healthy

older adults with high Ab amyloid on measures of executive function, at-

tention, visuoconstruction, and language. Conclusions: Adults with MCI

and high Ab amyloid presented with large impairments that were re-

stricted to episodic memory, while the episodic memory impairments in

MCI with low Ab amyloid were accompanied by additional impairments

in executive function, attention, visuoconstruction, and language. This

lends support to the hypothesis that MCI with high Ab amyloid reflects

the prodromal stage of AD, while MCI with low Ab amyloid may reflect

other causes of cognitive impairment.

P2-246 DISORIENTATION IN AMNESTIC MILD

COGNITIVE IMPAIRMENT IS CORRELATED

WITH HYPOMETABOLISM IN THE POSTERIOR

CINGULATE

So Moon, Ajou University, School of Medicine, Suwon, South Korea.

Contact e-mail: [email protected]

Background: A lesional study showed that three patients with right retro-

splenial lesions had intact performance in the part A of the card-placing

test (CPT) but impaired performance in the part B of the CPT. It was insisted

that the part A of the CPTassesses egocentric disorientation whereas part B

examines heading disorientation. However, the test has not yet been used in

any larger population. In addition, neural substrates of the test have not yet

been replicated in other studies. In our study, using statistical parametric

mapping (SPM) analysis we aimed to investigate anatomical correlates of

both part A and B of the CPT in FDG-PET studies of patients with amnestic

mild cognitive impairment (aMCI). Methods: A total of 15 aMCI patients

were enrolled into the study. Patients underwent standardized neuropsycho-

logical tests and part A and part B of the CPT. The CPT scores and K-MMSE

scores of 29 cognitively normal people were used for comparison. FDG-

PETwas performed in the same patients. We used the SPM correlation anal-

ysis to extract the regions whose changes in regional cerebral metabolism

correlated significantly with part A and B of the CPT with adjustment of

age and sex of patients. Results: Controlling for age, sex, and education

years, the K-MMSE score and CPT B score was significantly lower in the

aMCI group (26.062.0 vs. 28.261.4, p<0.001, and 16.364.4 vs.

19.763.7, p¼0.011). However, CPTA scores did not significantly differ be-

tween the two groups (25.563.5 vs. 27.762.7, p¼0.055). The SPM analysis

showed that decrease in scores of part A correlated with hypometabolism in

bilateral precuneus, posterior cingulate gyri, right crus cerebelli, cerebellar

vermis, right anterior and middle cingulate gyri, right superior and middle

frontal gyri, left inferior parietal region, and the left angular gyrus. (uncor-

rected p<0.05). Decrease in scores of part B correlated with hypometabo-

lism in bilateral precuneus, middle and posterior cingulate gyri

(uncorrected p<0.005). Conclusions: The test scores of part B of the card

placing test correlated well with hypometabolism of the posterior cingulate

gyrus and its surrounding areas whereas part A correlated with hypometab-

olism in more various areas.

P2-247 MODULATION OF BETA-AMYLOID-RELATED

COGNITIVE DECLINE BY BRAIN-DERIVED

NEUROTROPHIC FACTOR VAL66MET

POLYMORPHISM IN PRECLINICAL

ALZHEIMER’S DISEASE

Yen Ying Lim1, Victor Villemagne2, Simon Laws3, David Ames4,

Robb Pietrzak5, Kathryn Ellis6, Karra Harrington7, Pierrick Bourgeat8,

Olivier Salvado8, David Darby6, Peter Snyder9, Ashley Bush10,

Page 2: Modulation of beta-amyloid-related cognitive decline by brain-derived neurotrophic factor Val66Met polymorphism in preclinical Alzheimer's disease

Poster Presentations: P2 P447

Ralph Martins11, Colin Masters6, Christopher Rowe12, Pradeep Nathan13,

Paul Maruff14, 1University of Melbourne, Parkville, Australia; 2Austin

Health, Melbourne, Australia; 3Edith Cowan University, Joondalup,

Australia; 4National Ageing Research Institute Inc. (NARI), Parkville,

Australia; 5Yale University School of Medicine, New Haven, Connecticut,

United States; 6Mental Health Research Institute, Parkville, Australia; 7The

Mental Health Research Institute of Victoria, Parkville, Australia; 8CSIRO,

Herston, Australia; 9Brown University, Providence, Rhode Island, United

States; 10Mental Health Research Institute, Parkville, VIC, Australia;11Edith Cowan University, Perth, Australia; 12Austin Hospital, Melbourne,

Australia; 13GlaxoSmithKline and University of Cambridge, Cambridge,

United Kingdom; 14CogState Ltd, Melbourne, Australia. Contact e-mail: y.

[email protected]

Background: Brain-derived neurotrophic factor (BDNF) Val66Met poly-

morphism has previously been implicated in Alzheimer’s disease (AD)-re-

lated cognitive impairment. We aimed to determine whether BDNF

Val66Met moderates A b amyloid-related cognitive decline, reduction in

hippocampal volume, and A b amyloid accumulation in healthy older

adults. Methods: Healthy older adults (n¼165) enrolled in the Australian

Imaging, Biomarkers and Lifestyle (AIBL) study underwent positron

emission tomography (PET) neuroimaging for Ab amyloid using Pitts-

burgh Compound B (PiB), BDNF genotyping, and cognitive assessment

at baseline, 18- and 36-months. Linear mixed models determined rates

of change in cognition, hippocampal volume and A b amyloid accumula-

tion over 36 months. Results: In healthy older adults with high Ab amy-

loid, Met carriers showed significant and moderate-to-large decline in

episodic memory, executive function, and language, and greater reductions

in hippocampal volume over 36 months compared to Val/Val homozy-

gotes. BDNF Val66Met was unrelated to rates of change in cognition or

Table 1

Prevalence of different subtypes of mild cognitive impairment among all the elde

Normal aMCI-s

n of cases(% of total) 860(84.3) 65(6.4)

General mental status

MMSE 28.20(1.49) 26.97(1.63)

Memory function

AVLT-delay recall 6.36(2.13) 2.19(1.40)

AVLT-T 32.82(7.71) 17.43(4.61)

ROCF-delay recall 14.39(5.83) 9.45(6.49)

Spatial processing

ROCF-Copy 33.87(2.79) 32.54(3.50)

CDT 25.35(3.18) 24.77(7.20)

Language

CVFT 46.95(7.94) 40.28(7.22)

BNT 23.96(3.22) 22.46(3.60)

Attention

SDMT 37.19(10.26) 31.38(8.97)

TMT-A time (s) 55.11(22.00) 59.69(19.11)

Executive function

STROOPC-TIME 73.77(19.08) 80.83(22.63)

STROOPC-N 45.23(3.78) 44.98(3.42)

TMT-B time(s) 162.42(54.69) 177.49(52.25)

Abbreviations: aMCI-s, single domain amnestic mild cognitive impairment; aM

amnestic mild cognitive impairment; MMSE, Mini-Mental State Examination; AV

CDT, Clock-Drawing Test; CVFT, Category Verbal Fluency Test; BNT,Boston N

a: Post-hoc paired comparisons showed significant group differences between th

correction.

b: Post-hoc paired comparisons showed significant group differences between t

c: Post-hoc paired comparisons showed significant group differences between t

d: Post-hoc paired comparisons showed significant group differences between a

e: Post-hoc paired comparisons showed significant group differences between a

f: Post-hoc paired comparisons showed significant group differences between a

hippocampal volume in participants with low Ab amyloid. BDNF Val66-

Met was not associated with levels of Ab amyloid in participants with

high or low Ab amyloid levels at baseline. Similarly, BDNF Val66Met

was not associated with rates of Ab amyloid accumulation in participants

with high or low Ab amyloid levels at baseline. Conclusions: BDNF

Val66Met moderated the association between high A b amyloid and cogni-

tive decline and hippocampal atrophy in healthy older adults. High A b am-

yloid levels coupled with Met carriage may be useful prognostic markers of

accelerated cognitive decline and hippocampal degeneration in individuals

in the preclinical stage of AD.

P2-248 PREVALENCE AND PREDICTORS OF MILD

rly subjects bas

aMCI-m

38(

26.29(

1.68(

16.92(

6.00(

29.08(

22.76(

33.45(

19.53(

22.76(

85.81(

103.32(

40.05(

279.08(

CI-m, multipl

LT, Auditory Ve

aming Test; SD

e Normal group

he Normal gro

he Normal gro

MCI-s patient

MCI-s patients

MCI-m patient

COGNITIVE IMPAIRMENT INOLDAGE: RESULTS

FROM THE BABRI STUDY

Chao Ma, Junying Zhang, Xin Li, Ying Liang, Yaojing Chen,

Zhanjun Zhang, Beijing Normal University, Beijing, China. Contact e-mail:

[email protected]

Background: In recent years, the percentage of the elderly in the popula-

tion has been increasing in China and throughout the world. Consequently,

more and more patients suffer from aging related diseases, of which de-

mentia is a primary one. Alzheimer’s Disease (AD) is the most common

form of dementia and accounts for 60-80 percent of dementia. Mild cog-

nitive impairment (MCI) is associated with increased risk for dementia,

a higher percentage of people in this phase advance to AD than normally

people do. MCI patients have objective memory or other cognitive impair-

ments. Although MCI has been thought to be associated with increased

risks for dementia, longitudinal studies have also showed that MCI pa-

tients still have a good opportunity to recuperate under certain conditions.

ed on neuropsychological test scores

naMCI ANOVA

3.7) 57(5.6)

1.25) 26.91(1.76) <0.001a,b,c,d,f

1.36) 5.05(1.70) <0.001a,b,c,e,f

6.12) 26.79(5.94) <0.001a,b,c,e,f

4.13) 11.74(6.40) <0.001a,b,c,d,e,f

5.96) 31.96(3.46) <0.001a,b,c,d,f

6.22) 23.32(4.90) <0.001b,c,d,e

6.99) 40.61(7.12) <0.001a,b,c,d,f

4.17) 21.57(3.86) <0.001a,b,c,d,f

7.65) 27.98(9.70) <0.001a,b,c,d,f

39.13) 82.10(31.68) <0.001b,c,d,e

35.99) 101.81(30.42) <0.001a,b,c,d,e

5.72) 40.06(7.70) <0.001b,c,d,e

82.24) 248.82(76.71) <0.001a,b,c,d,e,f

e domain amnestic mild cognitive impairment; naMCI, non-

rbal Learning Test; ROCF, Rey-Osterrrieth Complex Figure;

MT, Symbol Digit Modalities Test; TMT,Trail Making Test

and aMCI-s patients, after least-significant difference (LSD)

up andaMCI-m patients, after LSD correction.

up andnaMCI patients, after LSD correction.

s andaMCI-m patients, after LSD correction.

andnaMCI patients, after LSD correction.

s andnaMCI patients, after LSD correction.