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

Introduction: Our objective was to investigate the effect of sex on cognitive decline within the context of amyloid beta (A beta) burden and apolipoprotein E genotype. Methods: We analyzed sex-specific effects on A beta-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, A beta-positron emission tomography, and apolipoprotein epsilon 4 were examined with quadratic time effects over a median of 4 years of follow-up. Results: Apolipoprotein epsilon 4 prevalence and A beta burden did not differ by sex. Sex did not directly influence cognitive decline. Females with higher A beta exhibited faster decline than males. Post hoc contrasts suggested that females who were A beta and apolipoprotein epsilon 4 positive declined faster than their male counterparts. Discussion: Although A beta did not differ by sex, cognitive decline was greater in females with higher A beta. Our findings suggest that sex may play a modifying role on risk of Alzheimer's disease-related cognitive decline. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.