Poster Presentations: P2 P397

P2-140 EFFECTS OF BETA-AMYLOID DEPOSITION AND

APOE-ε4 ON EPISODIC MEMORY: A LIFESPAN

APPROACH

Gerard Bischof1, Karen Rodrigue2, Kristen Kennedy3, Michael Devous3,

Denise Park4, 1University of Texas at Dallas, School for Behavioral and

Brain Sciences, Center for Vital Longevity, Dallas, Texas, United States;2Center for Vital Longevity, University of Texas at Dallas, Dallas, Texas,

United States; 3Center for Vital Longevity, University of Texas at Dallas,

Dallas, Texas, United States; 4University Of Texas at Dallas, Dallas, Texas,

United States. Contact e-mail: gerard.bischof@utdallas.edu

Background: Episodic memory decline is an early indicator for the onset of

Alzheimer’s Disease (AD). Additionally, episodic memory performance has

been linked to beta-amyloid (AB) pathology even in cognitively normal

older adults. Furthermore, apolipoprotein ε4 genotype (APOE ε4), a risk

factor for AD, has been associated with changes in cognition and some ev-

idence exists that across the lifespan APOE has both beneficial as well as

detrimental effects. Little knowledge exists about the synergistic effect of

APOE ε4 and amyloid on individual differences in episodic memory using

a lifespan approach. We therefore examined the effect of mean cortical AB

deposition and APOE ε4 on episodic memory in 147 healthy adults aged 30-

89 (Mean Age ¼63.4, Range¼ 30-89, Mean MMSE ¼29.3; 24% APOE

ε4+).Methods: Participants underwent PET imaging with F-18 Florbetapir.

Mean cortical AB SUVR was computed by extracting counts across 8 cor-

tical regions of interest, normalized to cerebellar gray matter. Additionally,

we computed a standardized memory construct for three tests of memory

(Hopkins Verbal Learning and Verbal RecognitionMemory). APOE ε4 gen-

otyping was done using venous blood samples. Results: APOE ε4 and AB

significantly related to recall memory scores in younger adults (30-49). Spe-

cifically, we found evidence for improved episodic memory performance in

APOE ε4 carrier in this younger population but a significant negative asso-

ciation of episodic memory performance and AB. In contrast, neither APOE

ε4 nor AB significantly related to episodic memory differences in middle-

aged adults (50-69). Finally, episodic memory differences in older adults

(70-89) were associated with AB in individuals only beyond the age of

80; no effect of APOE ε4 was found. Conclusions: These results suggest

that even in younger adults different levels of amyloid burden can impact

episodic memory performance. Additionally, the effect of APOE ε4 on

episodic memory performance may vary across the lifespan, as it was indic-

ative of better performance in younger adults only. Only with advanced age

are higher levels of amyloid associated with memory decrements. These

data underscore the utility of lifespan approaches and provide evidence

for an amyloid cascade that emerges earlier in the lifespan and can affect

episodic memory performance.

P2-141 THE ASSOCIATION BETWEEN

CARDIOVASCULAR RISK AND

NEUROCOGNITIVE MEASURES OF EXECUTIVE

FUNCTION INAT-RISK, COMMUNITY-DWELLING

OLDER ADULTS: AN FMRI STUDY

Yi-Fang Chuang1, Vijay Varma2, Gregory Haris2, Marilyn Albert3,

Linda Fried4, George Rebok5, Qian-Li Xue6, Michelle Carlson6, 1National

Institute on Aging, NIH, Baltimore, Maryland, United States; 2Johns

Hopkins, Baltimore, Maryland, United States; 3Johns Hopkins University,

Baltimore, Maryland, United States; 4Columbia University, New York,

New York, United States; 5John Hopkins University, Baltimore, Maryland,

United States; 6Johns Hopkins University, Baltimore, Maryland,

United States. Contact e-mail: yi-fang.chuang@nih.gov

Background: Cardiovascular (CV) risk factors, such as hypertension, dia-

betes, and hyperlipidemia are associated with cognitive impairment and

risk of dementia in the elderly. However, the mechanisms linking them

are not clear. This study aims to investigate the association between aggre-

gate CV risk and functional brain differences in a group of cognitively nor-

mal, community-dwelling older adults. Methods: Sixty participants (mean

age: 64.6 years) from the Brain Health Study (BHS), a nested study in Bal-

timore Experience Corps� Trial, underwent functional magnetic resonance

imaging (fMRI) at baseline using a test of executive function, the Flanker

task. We examined the correlation between aggregate CV risk measured

by the Framingham general cardiovascular risk profile (FGCRP) and neuro-

cognitive activity. Results: The mean FGCRP was 19.7%. 21.7% of partic-

ipants reported diagnosis of diabetes and 71.7% reported having

hypertension. Behaviorally, higher CV risk was associated with increased

interference on the Flanker task. Participants with higher CV also had

greater task-related activation in the left inferior parietal region and the

strength of this association increased with increasing executive demand.

Conclusions: The inferior parietal region is part of the dorsal attentional

network and has been implicated in early Alzheimer’s disease and mild cog-

nitive impairment. This study provides insights into the neural mechanisms

underlying the relationship between CV risk and cognitive aging and cogni-

tive impairment.

P2-142 SHORT-TERM PREDICTORS OF CLINICAL

PROGRESSION IN THE HARVARD AGING BRAIN

STUDY

Elizabeth Mormino1, Dorene Rentz2, Rebecca Amariglio3, Trey Hedden4,

Aaron Schultz5, Andrew Ward1, Gad Marshall3, Jasmeer Chhatwal1,

Nancy Donovan6, Kate Papp3, Brendon Boot7, Tamy-Fey Meneide1,

Natacha Lorius8, Sarah Wigman1, Alayna Younger1, Rebecca Betensky9,

John Becker1, Keith Johnson10, Reisa Sperling3, 1Massachusetts General

Hospital, Boston, Massachusetts, United States; 2Center for Alzheimer

Research and Treatment, Brigham andWomen’s Hospital, Harvard Medical

School, Boston, Massachusetts, United States; 3Brigham and Women’s

Hospital, Boston, Massachusetts, United States; 4Martinos Center for

Biomedical Imaging at Harvard University, Charlestown, Massachusetts,

United States; 5Massachusetts General Hospital, Charlestown,

Massachusetts, United States; 6Brigham and Women’s Hospital/Center for

Alzheimer Research and Treatment, Boston, Massachusetts, United States;7Harvard Medical School, Boston, Massachusetts, United States; 8Center

for Alzheimer Research and Treatment, Brigham and Women’s Hospital,

Charlestown, Massachusetts, United States; 9Harvard School of Public

Health, Boston, Massachusetts, United States; 10MGH HMS, Boston,

Massachusetts, United States. Contact e-mail: bmormino@nmr.mgh.

harvard.edu

Background:Within clinically normal (CN) older individuals, progression

towards global functional impairment may be influenced by levels of amy-

loid, neurodegeneration, and cognitive reserve. We examined the associa-

tion between these variables and progression from Clinical Dementia

Rating (CDR) global score 0 to 0.5 within CNs. Methods: We studied

169 CNs who had undergone at least 2 clinical visits and 1 baseline PIB-

PET scan at least 6 months prior to the final clinical visit (mean delay be-

tween PET and last clinical visit¼1.8 6 1.4yrs, range¼0.5-7.5yrs; mean

age¼746 7yrs). All subjects had a baseline CDRglobal score¼0, and a sub-

set of 125 CNs additionally completed baseline MRI. Distribution volume

ratio (DVR) images were created from the PIB-PET data and an aggregate

cortical PIB DVR value was extracted for each participant. Two PIB thresh-

olds were investigated (liberal¼1.15, conservative¼1.40). A composite of

verbal intelligence and the Hollingshead scale was used to measure cogni-

tive reserve. Hippocampal volume was derived using Freesurfer. Logistic

regression models were fit to assess the associations between CDR progres-

sion from 0 to 0.5, and PIB group, hippocampal volume, cognitive reserve,

age and gender. Additional models included interaction terms between PIB

and cognitive reserve, PIB and hippocampal volume, or hippocampal vol-

ume and cognitive reserve. Results: Seventeen subjects progressed to

CDR 0.5 at follow-up (10%). Subjects above the 1.40 PIB threshold were

more likely to progress (p¼0.02), whereas no significant difference was ob-

served using the 1.15 threshold (p¼0.79). The interaction between PIB and

cognitive reserve was not significant (p¼0.28). In the subset analysis of 125

subjects with MRI data, smaller hippocampal volume was significantly as-

sociated with progression (p¼0.03). There was a trend for an interaction be-

tween PIB and hippocampal volume (p¼0.14), such that a relationship

between hippocampus and progression was only present in high PIB sub-

jects. Furthermore, cognitive reserve interacted with hippocampal volume