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