The apolipoprotein E ε4 allele (APOE4) and family history of dementia (FH) are risk factors for the development of Alzheimer disease (AD). We assessed the effects of both APOE4 and FH on gray matter (GM) density in non-demented middle-aged adults in order to detect brain changes associated with increased risk for AD.
295 cognitively healthy middle-aged community-dwelling subjects underwent MRI scanning, APOE genotyping and assessment of FH. Voxel-based morphometry was used to study GM density differences between high- and low-risk subjects, based on APOE4 carriership (n=74), first-degree FH (n=227) or both (n=62). Structural brain images were processed and analyzed using VBM8 in SPM8. For statistical analysis, we used a cluster-forming threshold of p < 0.001 uncorrected with a minimal cluster size of 100 voxels.
APOE4 and FH were associated with reduced GM in different brain regions. APOE4 carriers had reduced GM in the striatum compared to non-carriers. Subjects with FH had reduced GM in right precuneus compared to subjects without FH. Maternal and paternal FH provided similar atrophy patterns. APOE4 carriers with FH had GM reductions in bilateral insula compared to subjects with no APOE4 and no FH (figure 1).