Alzheimer's & Dementia · Jul 2026

Sex differences in dementia pathology and cognitive performance in a population-based, ethnically diverse Brazilian autopsy study

By Socher KLR, Ferreira NV, Paes VR et al.

INTRODUCTION: Sex differences in dementia-related neuropathology are understudied in diverse populations. METHODS: We analyzed sex differences in neuropathological and cognitive data from the Brazilian Biobank for Aging Studies. Cognitive performance was evaluated with the Clinical Dementia Rating-Sum of Boxes (CDR-SOB). Linear and logistic regression models were conducted, including interaction terms for age, race, and education. RESULTS: In 2229 participants (50.7% female, mean age ± SD 75.4 ± 12.3 years, 62.1% White), female sex was associated with a higher odds of AD pathology (Braak: odds ratio [OR] = 1.42, 95% confidence interval [CI] = 1.17-1.72; Consortium to Establish a Registry for Alzheimer's Disease (CERAD): OR = 1.58, 95% CI = 1.27-1.98), and trans-activation response (TAR) DNA-binding protein 43 (TDP-43) (OR = 1.77, IC 95% = 1.22-2.59), and lower odds of Lewy body disease (OR = 0.69, 95% CI = 0.51-0.95). Female participant had worse cognitive performance (β = 1.56, 95% CI = 1.03-2.10). Sex modified associations of Braak, CERAD, TDP-43, and cerebral amyloid angiopathy with cognition. Age also interacted with sex and pathology on CDR-SOB. DISCUSSION: Sex differences in the associations between sex and neuropathology suggest the need for sex-informed dementia research.

doi.org/10.1002/alz.71691Open accessPubMed 42503573Populations