APOE ɛ4 Gene Dose and Sex Effects on Alzheimer’s Disease MRI Biomarkers in Older Adults with Mild Cognitive Impairment

Abstract

Background: APOE 4 and sex have been linked to increased risk for conversion to Alzheimer's disease (AD). However, the relationship between APOE 4 gene dose, sex, and AD biomarkers remains understudied. Objective: To investigate the effect of APOE 4 dose on AD biomarkers in a sample of older adults with mild cognitive impairment (MCI), and to examine whether APOE 4 dose modifies AD risk differently in MCI women and men. Methods: We examined cross-sectional AD biomarkers for participants with MCI (n = 930, 55-96 years old) from three large aging cohorts. Region of interest MRI volumes, global cognition, and episodic memory were analyzed by number of APOE 4 alleles and stratified by sex. Results: Across all participants, number of APOE 4 alleles was associated with smaller hippocampal and amygdala volumes and poorer cognition. When stratified by sex, women showed an APOE 4 dose effect for bilateral hippocampal and left amygdala volumes and cognition. In contrast, men showed an APOE 4 dose effect for hippocampal volumes with a trend in amygdala, but cognition did not differ between men with 1 and 2 APOE 4 alleles. Women with 2 APOE 4 alleles had poorer memory between 65-69 and poorer global cognition between 70-74 compared to men with 2 APOE 4 alleles. # Last authorship.

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