Sex, amyloid, and APOE ε4 and risk of cognitive decline in preclinical Alzheimer's disease: Findings from three well-characterized cohorts

Abstract Introduction Our objective was to investigate the effect of sex on cognitive decline within the context of amyloid β (Aβ) burden and apolipoprotein E genotype. Methods We analyzed sex-specific effects on Aβ-positron emission tomography, apolipoprotein, and rates of change on the Preclinical Alzheimer Cognitive Composite-5 across three cohorts, such as the Alzheimer's Disease Neuroimaging Initiative, Australian Imaging, Biomarker and Lifestyle, and Harvard Aging Brain Study (n = 755; clinical dementia rating = 0; age (standard deviation) = 73.6 (6.5); female = 55%). Mixed-effects models of cognitive change by sex, Aβ-positron emission tomography, and apolipoprotein e4 were examined with quadratic time effects over a median of 4 years of follow-up. Results Apolipoprotein e4 prevalence and Aβ burden did not differ by sex. Sex did not directly influence cognitive decline. Females with higher Aβ exhibited faster decline than males. Post hoc contrasts suggested that females who were Aβ and apolipoprotein e4 positive declined faster than their male counterparts. Discussion Although Aβ did not differ by sex, cognitive decline was greater in females with higher Aβ. Our findings suggest that sex may play a modifying role on risk of Alzheimer's disease–related cognitive decline.