APOE ?4 is associated with disproportionate progressive hippocampal atrophy in AD.

ABSTRACT:

Objectives

To investigate whether APOE ?4 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 ?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 ?4 carriers and non-carriers after adjustment for concurrent whole-brain atrophy rate was then calculated.

Results

Mean adjusted hippocampal atrophy rates in ?4 carriers were significantly higher in AD, MCI-P and MCI-S (p?0.011, all tests) compared with ?4 non-carriers. After adjustment for whole-brain atrophy rate, the difference in mean adjusted hippocampal atrophy rate between ?4 carriers and non-carriers was reduced but remained statistically significant in AD and MCI-P.

Conclusions

These results suggest that the APOE ?4 allele drives atrophy to the medial-temporal lobe region in AD.

SUBMITTER: Manning EN 

PROVIDER: S-EPMC4039513 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature