IC‐P‐047: Cerebral anatomical alterations in healthy middle‐aged ApoE4 carriers

ApoE ε4 carriers, specially the homozygous ones, are at increased risk for developing Alzheimer's Disease (AD). Healthy late-middle aged APOE4 carriers show alterations in brain regions known to be affected by AD. Conversely, there is controversy on whether, at these ages, asymptomatic APOE4 carriers display reduced hippocampal volumes, even though this is a characteristic feature by the time AD symptoms occur. In this work, we aimed at determining APOE4-associated structural changes in cognitively healthy late-middle age subjects in the whole brain and, specifically, in the hippocampus. A total of 238 subjects aged 45-65 were enrolled (107 noncarriers, 100 heterozygous and 31 homozygous) from the ALFA project. 3D-T1 weighted MRIs underwent VBM8-SPM (p<0.001) and Freesurfer (p<0.001) analyses for ε4 allele additive effects after correcting for intracranial volume, age and sex. Additionally, the hippocampal formation was further segmented into 8 subfields using Freesurfer which were subsequently analyzed (p<0.05). The VBM analysis revealed a cluster of ApoE ε4-associated volumetric decrease in the right hippocampus. Cortical thickness was bilaterally reduced in the precuneus, orbitofrontal and cingulate cortices as well as in small temporal, parietal and frontal regions. No between group differences could be detected in neither of the hippocampal subfields.