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Our study of subjects with mild cognitive impairment demonstrated that for the apolipoprotein E genotype, ε4 carriers exhibited markedly higher 1–4-year atrophy rates than ε3/ε3 homozygotes in 13 of 15 brain regions related to Alzheimer disease.


To determine the effect of the apolipoprotein E (APOE) genotype on atrophy rates of specific brain gray matter regions hypothesized to be key components of cognitive networks disrupted in Alzheimer disease.

Materials and Methods

The Alzheimer’s Disease Neuroimaging Initiative (ADNI) was approved by the institutional review boards of all participating sites. All subjects and their legal representatives gave written informed consent prior to data collection. The authors analyzed data from 237 subjects (mean age, 79.9 years; 40% female) with mild cognitive impairment (MCI) in the ADNI database and assessed the effect of the APOE ε4 and ε2 alleles on regional brain atrophy rates over a 12–48-month period. Brain regions were selected a priori: 15 experimental and five control regions were included. Regional atrophy rates were derived by using a fully automated algorithm applied to T1-weighted magnetic resonance (MR) imaging data. Analysis consisted of mixed-effects linear regression with repeated measures; results were adjusted for multiple testing with Bonferroni correction.


Thirteen of 15 experimental regions showed a significant effect of ε4 for higher atrophy rates (P < .001 for all). Cohen d values ranged from 0.26 to 0.42, with the largest effects seen in the amygdalae and hippocampi. The transverse temporal cortex showed a trend (P = .02, but did not survive Bonferroni correction) for a protective effect (Cohen d value = 0.15) of ε2. No control region showed an APOE effect.


The APOE ε4 allele is associated with accelerated rates of atrophy in 13 distinct brain regions in limbic and neocortical areas. This suggests the possibility of a genotype-specific network of related brain regions that undergo faster atrophy in MCI and potentially contribute to cognitive decline.

© RSNA, 2013

Online supplemental material is available for this article.


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Article History

Received May 6, 2013; revision requested June 13; revision received September 4; accepted September 19; final version accepted October 8.
Published online: Dec 12 2013
Published in print: Apr 2014