Sex Differences in in vivo Alzheimer's Disease Neuropathology in Late Middle-Aged Hispanics.

BACKGROUND: Females may have a higher risk of dementia than males. It is not clear if sex differences in Alzheimer's disease (AD) neuropathology explain the higher risk of dementia in females. Sex differences in AD neuropathology might begin in middle age, decades before the sex differences in dementia are apparent. OBJECTIVE: To examine sex differences in in vivo AD neuropathology in late middle age. METHODS: We conducted a cross-sectional comparison of AD biomarkers among 266 Hispanic males and females (mean age: 64.0; 71.8% females) without dementia. Amyloid burden was measured as global standardized uptake value ratio (SUVR) with18F-Florbetabenpositron emission tomography (PET). Neurodegeneration was ascertained as cortical thickness in AD signature areasusingbrain magnetic resonance imaging. Tau burden was measured as tau SUVR in the middle/inferior temporal gyri and medial temporal cortex with 18F-MK-6240 in 75 of the 266 participants. RESULTS: Females had higher amyloid SUVR and tau SUVR in the middle/inferior temporal gyri thanmales. However, femaleshad higher cortical thickness than males and performed better in a test of verbal memory despite having higher AD neuropathology burden. CONCLUSION: Higher amyloid and tauin femalescompared tomalesin late middle-agemay explainthe reported higher dementia risk in elderly females compared to males. Longitudinal follow-up is necessary to examine whether higher amyloid and tau burden in late middle age is followed by increased neurodegeneration and cognitive decline in females as compared with males.