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Updated: Jul 19, 2026

Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
Regional brain atrophy in cognitively intact adults with a single APOE epsilon4 allele
H A Wishart1, A J Saykin, T W McAllister
1Department of Psychiatry, Dartmouth Medical School/DHMC, Lebanon, NH 03756-0001, USA.
Objective:
To determine whether cognitively intact adults with the APOE epsilon3/epsilon4 genotype show reduced gray matter density on voxel-based morphometry (VBM) vs those homozygous for the epsilon3 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 epsilon3/epsilon3 genotype and 27 had the epsilon3/epsilon4 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 epsilon3/epsilon4 participants showed lower gray matter density than the epsilon3/epsilon3 participants in right medial temporal and bilateral frontotemporal regions as well as other areas. There were no regions in which epsilon3/epsilon4 participants showed higher gray matter density than epsilon3/epsilon3 participants.
Conclusions:
Regionally reduced gray matter density is detectable in cognitively intact adults with a single copy of the APOE epsilon4 allele.
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