Poster Presentation’s P1 S209

have been published on in vivo longitudinal brain amyloid changes in

cognitively normal (CN), mild cognitive impairment (MCI) and Alzheim-

er’s disease (AD). The purpose of this study is to investigate the change

of PIB retention after one-year follow up in CN old individuals and pa-

tients with MCI and AD. Methods: 22 CN, 19 MCI, and 19 mild AD sub-

jects were included. For each group, the proportion of apolipoprotein e4

positive cases was approximately 50% for each of the three groups. All

subjects underwent clinical assessments and PIB PET at two time points,

approximately one year apart. PIB retention was quantified in regional cor-

tical to cerebellar ratio units.Results: In CN, PIB retention at one-year fol-

low up increased significantly compared with baseline value in the diffuse

brain regions including the frontal, lateral temporal, medial temporal, lat-

eral parietal, posterior cingulate-precuneus (PC-PRC), and occipital corti-

ces, and basal ganglia. In contrast, such longitudinal increase of regional

PIB retention was observed only in the lateral parietal and PC-PRC for

MCI, and only in the PC-PRC for AD. Conclusions: The results of this

study indicate that the regional pattern of longitudinal PIB retention

change is different across the spectrum of cognitive ability. PIB retention

seems to be already saturated in diffuse cortical regions in MCI and early

clinical AD.

P1-308 NEW MRI MARKERS FOR ALZHEIMER’S

DISEASE: A META-ANALYSIS OF DIFFUSION

TENSOR IMAGING AND A COMPARISON WITH

MEDIALTEMPORAL LOBE MEASUREMENTS

Lies Clerx1, Pieter Jelle Visser2, Frans R. J. Verhey2, Pauline Aalten2,1Maastricht University, Maastricht, Netherlands; 2School for Mental

Health and Neuroscience (MHeNS), University Medical Centre, Maastricht,

Netherlands.

Background:Atrophy of the medial temporal lobe (MTL) as assessed on

structural MRI is a diagnostic marker for Alzheimer’s disease (AD). Re-

cently, new imaging modalities have been developed which may have di-

agnostic potential for AD as well. The aim of the present review was to

compare the diagnostic value of diffusion tensor imaging (DTI) with that

of MTL atrophy using a meta-analysis approach. A systematic literature

research was performed into DTI and MTL atrophy in AD and mild cog-

nitive impairment (MCI). Methods:We examined twenty-four studies on

MTL atrophy (data for 821 healthy controls (HC), 438 MCI, 725 AD) and

twenty-one DTI-studies (data for 337 HC, 129 MCI, 332 AD). The out-

come measure was the pooled effect-size (ES). Results: The ES of

MTL measures for the distinction between AD and HC was 1.83 for

MTA score (p < 0.001), 1.63 for hippocampus volume (p < 0.001),

1.72 for parahippocampal gyrus volume (p < 0.001)and 1.96 for entorhi-

nal cortex (ERC) volume (p < 0.001). For DTI, fractional anisotropy

(FA) in the following structures was significantly different between HC

and AD patients: frontal lobe (ES ¼ 0.67, p < 0.01); genu of the corpus

callosum (CC) (ES ¼ 0.56, p < 0.001); splenium of the CC (ES ¼ 0.75, p

< 0.01); and the temporal lobe (ES ¼ 0.54, p < 0.01). With regard to

mean diffusivity (MD) values, all the investigated structures were signif-

icantly different between HC and AD patients. ES ranged from 0.75 (oc-

cipital lobe) to 1.58 (parietal lobe). With regard to FA values, only the

splenium of the CC (ES ¼ 0.36, p < 0.05) was significantly different be-

tween MCI patients and HC. With regard to MD values, the following

structures significantly differed between HC and MCI patients: temporal

lobe (ES ¼ 0.39, p < 0.05); genu CC (ES ¼ 0.45, p < .05); and splenium

CC (ES ¼ 0.54, p < 0.01). No significant differences in FA or MD were

found between MCI and AD patients. Conclusions: Although the DTI

measures of HC differ from those of subjects with MCI and AD, the dis-

criminative power of DTI is less than that of MTL measures. Moreover,

our analysis reveals that DTI-MD values seem to have better discrimina-

tive power than DTI-FA values. Nevertheless, further DTI studies are

needed to investigate the added value of DTI for the early prediction of

AD in non-demented subjects.

P1-309 CORRELATIONBETWEEN BASELINEMEASURES

OFAMYLOID-POSITRON EMISSION

TOMOGRAPHY (PET) IMAGING, CEREBRAL

SPINAL FLUID (CSF) BIOMARKERS, AND

CLINICAL SCALES IN PREDEMENTIA

ALZHEIMER’S DISEASE

Vlad Coric1, John Seibyl2, Mark Mintun3, Joel Ross4, Mark Brody5,

Craig Curtis6, Ralph Richter7, Wendy Hayes8, Brian McHugh8,

Bongin Yoo1, Kenneth Marek9, Joshua Grill10, Howard Feldman1,

Robert Berman1, 1Bristol-Myers Squibb, Wallingford, Connecticut, United

States; 2Institute for Neurodegenerative Disorders, New Haven,

Connecticut, United States; 3Avid Radiopharmaceuticals, Inc.,

Philadelphia, Pennsylvania, United States; 4Memory Enhancement Center

of America, Inc. (MECA), Eatontown, New Jersey, United States; 5Brain

Matters Research, Delray Beach, Florida, United States; 6Compass

Research, LLC, Orlando, Florida, United States; 7Tulsa Clinical Research

LLC, Tulsa, Oklahoma, United States; 8Bristol-Myers Squibb, Princeton,

New Jersey, United States; 9Molecular NeuroImaging, New Haven,

Connecticut, United States; 10Mary S. Easton Center for AD Research at

UCLA, Los Angeles, California, United States.

Background: CSF amyloid and tau biomarkers are strong predictors of AD

progression from mild cognitive impairment (MCI). Emerging clinical evi-

dence suggests that amyloid-PET imaging has similar utility. The correla-

tion between CSF and PET amyloid biomarkers is expected to be high in

AD. Methods: We performed an exploratory analysis limited to baseline

data from predementia AD patients (identified by CSF biomarker measure-

ments) enrolled in CN156018 who completed florbetapir (florbetapir F 18

[18F-AV-45]) amyloid-PET scans to examine: 1) concordance between path-

ologic CSF (low CSF Aß42, high total-tau [t-tau]) and florbetapir-PET vi-

sual analysis, 2) correlation between t-tau/Aß42 ratio and quantitative

florbetapir PET standard uptake volume ratios (SUVRs), and 3) correlation

between clinical rating scales and amyloid CSF and PET biomarkers.

CN156018 is an ongoing, randomized, double-blind, placebo-controlled,

Phase 2 study designed to assess the safety and tolerability of BMS-

708163, a gamma secretase inhibitor, in patients with predementia AD.

Approximately 100 patients will complete both CSFmeasurements and flor-

betapir PET imaging. Study entry criteria include: male and female outpa-

tients 45-90 years of age, CSF Aß42 � 200 pg/mL or t-tau/Aß42 ratio �0.39, MMSE score 24-30 (inclusive), subjective memory complaint, objec-

tive memory loss measured by education adjusted scores onWechsler Mem-

ory Scale Logical Memory II or the Free Cued Selective Reminding Test

(FCSRT), and Clinical Dementia Rating scale global score of 0.5 with

a memory box score of ¼ 0.5. Results: Eighteen of the first 20 patients en-

rolled in CN156018 demonstrated concordance between pathologic CSF

(low CSFAß42 and high t-tau) and amyloid positive florbetapir-PET visual

analysis at baseline. Quantitative analyses of amyloid burden using florbe-

tapir-PET imaging at baseline demonstrated statistically significant correla-

tions (Pearson correlation ¼ 0.76 to 0.80, P < 0.05; N ¼ 24) between

SUVRs and CSF t-tau/Aß42 ratio at baseline. Among clinical scales,

FCSRT demonstrated the highest correlation with both amyloid CSF and

florbetapir-PET SUVR at baseline. Conclusions: Consistent with the diag-

nostic framework proposed by Dubois et al, the relationship between path-

ologic CSF (low CSF Aß42, high t-tau) and amyloid-PET uptake values

observed in initial participants in CN156018 demonstrate that multiple sup-

portive amyloid biomarkers can be used to potentially identify patients with

predementia AD.

P1-310 CORRELATIONS BETWEEN AMYLOID AND

METABOLIC PET IMAGING IN COGNITIVELY

NORMAL ADULTS WITH A FAMILY HISTORY OF

LATE-ONSETALZHEIMER’S DISEASE

MeganCummings1, Juha Rinne2, LisaMosconi3,Wai Tsui1, JohnMurray3,

Yi Li1, Lidia Glodzik1, Pauline McHugh1, Schantel Williams1,

Stanley Goldsmith4, Shankar Vallabhajosula4, Noora Scheinin2,

Poster Presentation’s P1S210

Tapio Viljanen2, Kjell Nagren2, Mony De Leon1, 1NYU Center for Brain

Health, New York, New York, United States; 2Turku PET Centre, Turku,

Finland; 3NYU School of Medicine, New York, New York, United States;4Cornell University, New York, New York, United States.

Background: Having a parent affected with late-onset Alzheimer’s dis-

ease (LOAD) is a major risk factor among cognitively normal (NL) in-

dividuals. This study examines whether NL with LOAD-parents show

preclinical evidence of brain AD, as reflected in increased fibrillar amy-

loid-beta (Aß) deposition on C-Pittsburgh Compound B (PiB)-PET, a

major hallmark of AD pathology, and reduced glucose metabolism on18F-fluorodeoxyglucose (FDG)-PET, a proxy for neuronal dysfunction.

Methods: Forty-five 40-80 year-old NL with 8F-FDG and 11C-PIB PETex-

aminations were examined, including 15 NL with a maternal history (MH),

15 NL with a paternal history (PH), and 15 NL with negative family history

of LOAD (NH). For all cases, the parents’ AD diagnosis was clinician cer-

tified. Automated regions-of-interest, statistical parametric mapping, voxel-

wise inter-modality correlations and logistic regression were used to exam-

ine cerebral-to-cerebellar PiB and FDG standardized uptake value ratios

across groups. Results: Groups were comparable for clinical and demo-

graphical measures. The MH group showed higher PiB retention and lower

metabolism in AD-regions compared to NH and PH, while the PH group

showed milder PiB increases and no metabolic reductions compared to

NH. Results remained significant controlling for age, gender, education

and ApoE. Metabolism and PiB retention were negatively correlated locally

in PCC, frontal and parieto-temporal regions in MHPY, whereas no correla-

tions were observed in NH and PH. The combination of Aß deposition and

metabolism improved group separation over either measure alone, yielding

� 65% accuracy for MH vs NH and PH (P < 0.05). Conclusions: Among

NL with LOAD-parents, only MH show co-occurring Aß increases and hy-

pometabolism in AD-vulnerable regions, suggesting that these subjects may

be at a MHPY increased risk for AD than PH. Present findings maymotivate

further research on familial transmission and parent-of-origin effects in

LOAD, and indicate a great need for early intervention trials targeting adult

children of LOAD-parents.

P1-311 TESTING THE NEW DIAGNOSTIC CRITERIA FOR

PRECLINICAL ALZHEIMER’S DISEASE: MRI

BIOMARKER OFALZHEIMER’S DISEASE-

RELATED ATROPHY IN COGNITIVELY

NORMAL INDIVIDUALS PREDICTS

COGNITIVE DECLINE

Brad Dickerson1, David Wolk2, 1MGH/Harvard Medical School,

Charlestown, Massachusetts, United States; 2University of Pennsylvania,

Philadelphia, Pennsylvania, United States.

Background:New diagnostic criteria have been developed for the detec-

tion of Preclinical AD using biomarkers in cognitively normal (CN) older

adults. We implemented these criteria using an MRI biomarker previ-

ously demonstrated to be associated with Alzheimer’s disease (AD) de-

mentia to test the hypothesis that individuals classified as Preclinical

AD using this marker would be at elevated risk for cognitive decline con-

sistent with symptoms of early AD. Methods: The ADNI dataset was in-

terrogated for CN individuals. MRI data were processed to obtain cortical

thickness measures using a previously published set of a priori regions of

interest to derive a single composite measure known as the “AD-signature”

(ADsig). Each individual was then classified as ADsig-Low consistent with

Preclinical AD (> 1S.D. below the mean), ADsig-Average (within 1 S.D. of

the mean), or ADsig-High (> 1 S.D. above the mean). A three-year Cogni-

tive Decline outcome was defined a priori using change in CDRSum-of-

Boxes and selected neuropsychological measures. We hypothesized that

Preclinical AD individuals would be at elevated risk of Cognitive Decline.

Results:Of the 125 individuals whowere CN at baseline, the19 classified as

Preclinical AD using the MRI biomarker were at markedly increased risk of

Cognitive Decline, which developed in 21% of them compared with 7% of

ADsig-Average and 0% of ADsig-High groups (p¼ 0.03). A logistic regres-

sion model demonstrated that every 1 S.D. of cortical thinning was associ-

ated with a nearly tripled risk of Cognitive Decline (p ¼ 0.02). In addition,

of those for whom baseline cerebrospinal fluid (CSF) data were available,

60% of the Preclinical AD group had CSF characteristics consistent with

AD while 36% of the AD-sig Average and 19% of the AD-sig High groups

had such CSF characteristics (p¼ 0.1). Conclusions: The present data sup-

ports our hypothesis that this approach to the detection of Preclinical AD-

identified in single NC individuals using this quantitative AD-signature

MRI biomarker-may provide investigators with a population enriched for

AD pathobiology and at relatively high risk for imminent cognitive decline

consistent with prodromal AD.

P1-312 CORTICALTHICKNESS COMPARISON BETWEEN

PIB-POSITIVE AND PIB-NEGATIVE HEALTHY

CONTROL PATIENTS

Vincent Dore1, Pierrick Bourgeat1, Jurgen Fripp1, Oscar Acosta2,

Gael Chetelat3, Cassandra Szoeke4, Kathryn Ellis5, Ralph Martins6,

Victor Villemagne7, Colin Masters8, David Ames5, Christopher Rowe7,

Olivier Salvado1, 1CSIRO Preventative Health National Research Flagship

ICTC, The Australian e-Health Research Centre-BioMedical, Brisbane,

Australia; 2Universit�e de Rennes 1, LTSI, Rennes, France; 3Department of

NuclearMedicine and Centre for PET, andDepartment ofMedicine, University

of Melbourne, Austin Hospital, Melbourne, Australia; 4CSIRO Parkville,

Melbourne, Australia; 5Academic Unit for Psychiatry of Old Age, Department

of Psychiatry, The University of Melbourne, St. Vincent’s Aged Psychiatry

Service, St George’s Hospital, Melbourne, Australia; 6Centre of Excellence for

Alzheimer’s Disease Research & Care, School of Exercise Biomedical and

Health Sciences,, Perth, Australia; 7Austin Health, Melbourne, Australia; 8The

Mental Health Research Institute, Melbourne, Australia.

Background: Studies have showed that B-amyloid plaques are likely to

only exhibit local affects on the cortex at early stages of the disease before

or when early cognition impairments occur. Understanding when and where

neurodegeneration starts in the cortex may provide insights into the patho-

genesis of AD. In this study, we focus on elderly Healthy Control (HC).

While the majority of subjects in this group have low neocortical PiB reten-

tion (PiB SURV< 1.5), some present high PiB retention (PiB SURV>¼1.5),

which is often seen as prodromal AD. In this abstract, we first identify dis-

criminating regions using AD/PiB-negative HC analysis to then find differ-

ence between PiB-positive HC and PiB-negative HC. Methods: 119

subjects underwent a MRI scan and a 11C-PIB PET scans as part of the