APOE ε4 Is Associated with Disproportionate Progressive Hippocampal Atrophy in AD.


Manning, EN; Barnes, J; Cash, DM; Bartlett, JW; Leung, KK; Ourselin, S; Nick C. Fox1 for the Alzheimer's Disease NeuroImaging Initiative, ; (2014) APOE ε4 Is Associated with Disproportionate Progressive Hippocampal Atrophy in AD. PLoS One, 9 (5). e97608. ISSN 1932-6203 DOI: https://doi.org/10.1371/journal.pone.0097608

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Abstract

OBJECTIVES To investigate whether APOE ε4 carriers have higher hippocampal atrophy rates than non-carriers in Alzheimer's disease (AD), mild cognitive impairment (MCI) and controls, and if so, whether higher hippocampal atrophy rates are still observed after adjusting for concurrent whole-brain atrophy rates. METHODS MRI scans from all available visits in ADNI (148 AD, 307 MCI, 167 controls) were used. 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 hippocampal and whole-brain atrophy rates, adjusting for age, gender, MMSE and brain-to-intracranial volume ratio. The difference in hippocampal rates between ε4 carriers and non-carriers after adjustment for concurrent whole-brain atrophy rate was then calculated. RESULTS Mean adjusted hippocampal atrophy rates in ε4 carriers were significantly higher in AD, MCI-P and MCI-S (p≤0.011, all tests) compared with ε4 non-carriers. After adjustment for whole-brain atrophy rate, the difference in mean adjusted hippocampal atrophy rate between ε4 carriers and non-carriers was reduced but remained statistically significant in AD and MCI-P. CONCLUSIONS These results suggest that the APOE ε4 allele drives atrophy to the medial-temporal lobe region in AD.

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Medical Statistics
PubMed ID: 24878738
Web of Science ID: 338101500018
URI: http://researchonline.lshtm.ac.uk/id/eprint/1775873

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