Sex and APOE genotype differences in amyloid deposition and cognitive performance along the Alzheimer’s Continuum

Abstract

Conflicting findings exist regarding the differences in amyloid burden and cognitive performance based on sex and apolipoprotein E (APOE) genotype. This study aimed to investigate the brain amyloid-β (Aβ) burden and cognitive performances by sex and APOE genotype in a cohort of Aβ-positron emission tomography (PET)–positive participants. Brain Aβ burden was assessed using 18F-florbetapir PET standard uptake value ratios. Cognitive performance was evaluated using standardized neuropsychological tests. In the cognitively normal participants, females had a higher Aβ burden than males in APOE ε4 noncarriers, whereas APOE ε4 carriers had a higher Aβ burden than noncarriers in males. In the cognitively impaired participants, APOE ε4 carriers were more likely to have a higher Aβ burden than noncarriers in the brain regions of the lateral parietal gyrus, frontal gyrus, and precuneus. In addition, females were more likely to have poorer language and visuospatial performance compared to males, while the APOE genotype did not significantly impact cognitive performance. These findings further elucidate the impact of sex and APOE genotype on brain Aβ burden and sex-related cognitive performance should be considered in the Alzheimer’s Continuum.