Regional brain atrophy in cognitively intact adults with a single APOE ε4 allele

Objective: To determine whether cognitively intact adults with the APOE epsilon 3/epsilon 4 genotype show reduced gray matter density on voxel-based morphometry (VBM) vs those homozygous for the epsilon 3 allele. Methods: Participants were healthy, cognitively intact, right-handed adults, age 19 to 80, who completed genotyping, neuropsychological testing, and MRI. Forty-nine participants had the epsilon 3/epsilon 3 genotype and 27 had the epsilon 3/epsilon 4 genotype. Gray matter data were analyzed using the general linear model as implemented in the Statistical Parametric Mapping package, adjusting for age and sex. Results: The epsilon 3/epsilon 4 participants showed lower gray matter density than the epsilon 3/epsilon 3 participants in right medial temporal and bilateral frontotemporal regions as well as other areas. There were no regions in which epsilon 3/epsilon 4 participants showed higher gray matter density than epsilon 3/epsilon 3 participants. Conclusions: Regionally reduced gray matter density is detectable in cognitively intact adults with a single copy of the APOE epsilon 4 allele.