APOE epsilon 4 Is Associated with Disproportionate Progressive Hippocampal Atrophy in AD

作者：Manning Emily N^*; Barnes Josephine; Cash David M; Bartlett Jonathan W; Leung Kelvin K; Ourselin Sebastien; Fox Nick C

来源：PLos One, 2014, 9(5): e97608.

DOI：10.1371/journal.pone.0097608

Objectives: To investigate whether APOE epsilon 4 carriers have higher hippocampal atrophy rates than non-carriers in Alzheimer%26apos;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. %26lt;br%26gt;Methods: MRI scans from all available visits in ADNI (148 AD, 307 MCI, 167 controls) were used. MCI subjects were divided into %26quot;progressors%26apos;%26apos; (MCI-P) if diagnosed with AD within 36 months or %26quot;stable%26apos;%26apos; (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 epsilon 4 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 epsilon 4 carriers and non-carriers after adjustment for concurrent whole-brain atrophy rate was then calculated. %26lt;br%26gt;Results: Mean adjusted hippocampal atrophy rates in epsilon 4 carriers were significantly higher in AD, MCI-P and MCI-S (p %26lt;= 0.011, all tests) compared with epsilon 4 non-carriers. After adjustment for whole-brain atrophy rate, the difference in mean adjusted hippocampal atrophy rate between epsilon 4 carriers and non-carriers was reduced but remained statistically significant in AD and MCI-P. %26lt;br%26gt;Conclusions: These results suggest that the APOE epsilon 4 allele drives atrophy to the medial-temporal lobe region in AD.

• 出版日期2014-5-30