Abstract

Abstract Objective Extant literature demonstrates increased risk of Alzheimer’s Disease (ad) and hippocampal degeneration with hypertension. Less is known about blood pressure (BP) and APOE4 effects, and their interaction on hippocampal volume. We hypothesized that the effects of elevated mean arterial pressure (MAP) on hippocampal volume would be stronger among those with at least one APOE4 allele. We further hypothesized that MAP effects would be stronger in an ad group than either mild cognitive impairment (MCI) or control groups, and stronger in MCI than controls. Methods Participants (N = 965; 46.4% female; 92.9% White; 56.7% MCI, 18.3% ad) were selected from the ad Neuroimaging Initiative database. Inclusion criteria: complete demographics, diagnostic evaluation, APOE genotyping (46.6.% APOE4 positive), BP measurements (mean MAP = 94.55mmg3 (SD = 10.41)), and MRI. Hippocampal volume was quantified using FreeSurfer 5.3 (bilateral mean = 6844.51 mm3 (SD = 1191.68)). The sample age was 72.84 (SD = 7.55) with 16.02 (SD = 2.77) years of education on average. Results Although MAP and APOE4 each significantly accounted for variance in bilateral and each hippocampal volume using a hierarchical multiple quadratic regression, the interaction of MAP and APOE4 did not (see Table). Similarly, while MAP and diagnostic group were each found to significantly account for variance in hippocampal volumes, their interactions did not. Conclusions Results are consistent with previous findings that higher BP negatively impacts hippocampal volume. However, interaction hypotheses were not supported. Therefore, APOE4 and MAP may represent independent mechanisms in ad pathology. However, antihypertensive medication effects, which may mitigate hippocampal atrophy, were not assessed. Future investigations might control medication effects and investigate homogenous versus heterogeneous APOE variants.

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