Sex differences in functional and molecular neuroimaging biomarkers of Alzheimer's disease in cognitively normal older adults with subjective memory complaints

Abstract Introduction Observational multimodal neuroimaging studies indicate sex differences in Alzheimer's disease pathophysiological markers. Methods Positron emission tomographybrain amyloidload, neurodegeneration (hippocampus and basal forebrainvolumes adjusted to total intracranial volume, cortical thickness, and 2-deoxy-2-[fluorine-18]fluoro-D-glucose– positron emission tomographymetabolism), and brain resting- state functionalconnectivity were analyzed in 318 cognitively intact older adults from the INSIGHT-preAD cohort (female n = 201, male n = 117). A linear mixed-effects model was performed to investigate sex effects and sex∗ apolipoprotein Egenotype interaction on each marker as well as sex∗ amyloidgroup interaction for non- amyloidmarkers. Results Men compared with women showed higher anterior cingulate cortex amyloidload ( P = .009), glucose hypometabolism in the precuneus( P = .027), posterior cingulate( P P = .043) cortices, and lower resting- state functionalconnectivity in the default mode network( P = .024). No brain volumetric markers showed differences between men and women. Sex∗ apolipoprotein Egenotype and sex∗ amyloidstatus interactions were not significant. Discussion Our findings suggest that cognitively intact older men compared with women have higher resilience to pathophysiological processes of Alzheimer's disease.