Sex Differences in Alzheimer Disease Imaging Biomarkers in a Diverse, Community-Based Cohort

Abstract

Importance Sex differences in Alzheimer disease (AD) neuropathology have not been examined extensively across multiple pathological constructs within broadly representative samples. Objective To examine sex differences in neuroimaging biomarkers of AD-related pathologies in a racially and ethnically diverse cohort. Design, Setting, and Participants Data for this cross-sectional study were collected from a community-based sample of adults without cognitive impairment aged 60 to 69 years in New York City from March 1, 2016, to September 31, 2022, and analyzed in March 2025. Exposure The primary exposure was self-reported sex (women or men). Main Outcomes and Measures The outcomes were global amyloid burden measured with florbetaben labeled with fludeoxyglucose 18 (18F) positron emission tomography (PET), tau burden in Braak stages I to VI measured with 18F-MK-6240 PET, and magnetic resonance imaging (MRI)–derived AD signature cortical thickness and white matter hyperintensity volumes. Linear regression analyses were performed to examine sex differences in the outcomes. Covariates included demographics, APOE ε4 status, and vascular health–related factors. Sex × age, sex × APOE ε4, and sex × race and ethnicity interactions were additionally examined on the outcomes. False discovery rate (FDR) correction for multiple comparisons were also performed. Results A total of 503 participants (mean [SD] age, 64.6 [2.8] years; 321 [63.8%] women; 305 [60.6%] Hispanic, 120 [23.9%] non-Hispanic Black, and 78 [15.5%] non-Hispanic White) with Aβ PET, MRI (n = 501), and tau PET (n = 355) data were studied. Compared with men, women had greater amyloid burden (B = 0.05; 95% CI, 0.02-0.07; P