Figure. Patterns of glucose metabolism (FDG-PET) and amyloid deposi-

tion (PIB-PET) in ApoE4+ AD and ApoE4- AD subjects. A) Differences

in ApoE groups compared with controls. Maps show t-values corrected

for multiple comparisons (FWE p<0.05). B) Direct comparison between

ApoE AD groups. Shown are statistical t-maps at uncorrected threshold

of p<0.01 for FDG, and FWE-corrected (p<0.05) for PIB ApoE4- >

ApoE4+, and uncorrected at p<0.05 for ApoE4+ > ApoE4-. Shown are

also percent difference maps (-10% to 10%) to provide a fuller characteriza-

tion of the FDG and PIB patterns, with red indicating higher FDG/PIB up-

take in the ApoE4-patients compared with ApoE4+, and blue indicating the

reverse contrast.

Oral Sessions: IC-O1: Imaging Populations at Genetic Risk for Alzheimer’s Disease P5

for comparison. Subjects underwent PET imaging with PIB (to measure am-

yloid) and FDG (to measure glucose metabolism). Voxel-wise comparisons

of FDG and PIBwere performed between groups. Analyses were adjusted for

age, gender and education, with additional correction for MMSE in the be-

tween-patient group comparisons. Differences between controls and patients

were corrected for multiple comparisons, whereas between-patient group

differences are shown at different statistical thresholds and as percent differ-

ences (see Figure).Results:Whilst PIB patterns were diffuse in both ApoE

groups, ApoE4- patients showed higher PIB uptake than ApoE4+ patients

across the cortex (Figure). Higher PIB uptake in ApoE4- was particularly

significant in right lateral frontotemporal regions. In contrast, similar pat-

terns of hypometabolism relative to controls were found in both ApoE

groups, mainly involving lateral temporoparietal cortex, precuneus, poste-

rior cingulate cortex, and middle frontal gyrus. Comparing patient groups,

ApoE4+ subjects showed greater hypometabolism in bilateral medial tem-

poral and right lateral temporal regions, and ApoE4- patients showed

greater hypometabolism in cortical areas including supplementary motor

cortex and superior frontal gyrus. Results were unchanged after applying

Adjusted mean difference in atrophy rate (%/year) [95% CI] for ε4 carriers comp

controls (n¼167) MCI sta

Difference in mean adjusted* whole brain

atrophy rate (%/year)

-0.003 [-0.12, 0.11]

p¼0.958

-0.24 [-0

p¼0.001

Difference in mean adjusted* hippocampal**

atrophy rate (%/year)

-0.02 [-0.45, 0.40]

p¼0.914

-0.80 [-1

p¼0.012

Difference in mean adjusted* hippocampal**

atrophy rate (%/year) after adjustment for

concurrent whole brain atrophy

-0.02 [-0.38, 0.34]

p¼0.925

-0.27 [-0

p¼0.364

*All values were adjusted for disease-group specific mean age, baseline brain t

**Average of left and right.

atrophy correction to the PET data. Conclusions: ApoE4-carriers showed

a similar degree of hypometabolism in the presence of lower amyloid bur-

den than matched ApoE4-noncarriers, suggesting greater metabolic vulner-

ability in ApoE4-carriers that is not explained by Ab burden. Small

reductions in metabolism in medial temporal regions in ApoE4-carriers

correspond to the reported link between ApoE4 and an amnestic clinical

phenotype in AD.

IC-O1-05 APOE-ε4 IS ASSOCIATEDWITH INCREASED

ared with non-

ble (n¼169)

.38, -0.10]

.42, -0.18]

.84, 0.31]

o total intracra

HIPPOCAMPAL ATROPHY RATES IN

ALZHEIMER’S DISEASE

Emily Manning1, Josephine Barnes1, David Cash1, Jonathan Bartlett2,

Kelvin Leung3, Sebastien Ourselin1, Nick Fox3, 1University College

London, London, United Kingdom; 2London School of Hygiene and Tropical

Medicine, London, United Kingdom; 3UCL Institute of Neurology, London,

United Kingdom. Contact e-mail: e.manning@ucl.ac.uk

Background: Previous studies have reported higher hippocampal atrophy

rates in APOE ε4 carriers (ε4+) compared with non-carriers (ε4-) in AD.

However the modulating effect of the APOE gene on brain and hippocam-

pal atrophy at different stages of AD is unclear. We aimed to investigate

whether ε4+ carriers have higher brain and hippocampal atrophy rates

compared with non-carriers in Alzheimer’s disease (AD), mild cognitive

impairment (MCI) and controls and if so, whether higher hippocampal

rates are observed after adjusting for brain atrophy rate. Methods: MRI

scans from all visits in ADNI (148 AD, 307 MCI, 167 controls) were

used. Hippocampal and brain atrophy rates were calculated using the

boundary shift integral. MCI subjects were divided into "progressors"

(MCI-P) if diagnosed with AD within 36 months or "stable" (MCI-S) if

a diagnosis of MCI was maintained. A joint multi-level mixed-effect linear

regression model was used to analyse the effect of ε4 carrier-status on hip-

pocampal and brain atrophy rates, adjusting for age, gender, MMSE and

brain-to-intracranial volume ratio. The difference in hippocampal rates be-

tween ε4+ and ε4- after adjustment for concurrent brain atrophy rate was

then calculated. Results: Mean adjusted whole brain atrophy rates were

higher in ε4+ compared with ε4- in AD, MCI-P and MCI-S although

this was only significant in MCI-S. Mean adjusted hippocampal atrophy

rates in ε4+ were significantly higher in AD, MCI-P and MCI-S

(p�0.055, all tests) compared with ε4- (see table). After adjustment for

brain atrophy rate, the difference in mean adjusted hippocampal atrophy

rate between ε4+ and ε4- was reduced (by w70% in MCI_S, w40% in

MCI-P and w30% in AD). There was borderline evidence that brain-

rate-adjusted hippocampal atrophy rate was higher in AD ε4+,

(p¼0.060) but not in MCI-P or MCI-S. Conclusions: These findings

show that hippocampal atrophy rates in ε 4+ are higher than in ε 4- in AD

andMCI. Some of this difference is explained by higher brain atrophy rates,

however there is borderline evidence that hippocampal atrophy rates in ε 4+

are higher than ε 4- after adjusting for concurrent brain atrophy rates. These

results suggest that the APOE ε 4 allele drives atrophy to the medial-tempo-

ral lobe region in AD.

carriers in controls, stable MCI, MCI progressors and AD

MCI progressors (n¼138) AD (n¼148)

-0.15 [-0.37, 0.06]

p¼0.157

-0.17 [-0.40, 0.04]

p¼0.113

-0.92 [-1.85, 0.02]

p¼0.055

-1.32 [-2.4, -0.27] p¼0.014

-0.53 [-1.31, 0.25]

p¼0.182

-0.88 [-1.81, 0.04]

p¼0.060

nial volume ratio, MMSE score and gender.