Sex Differences in the Associations between Education, Neuropathology, and Cognition

Abstract IMPORTANCE Autopsy evidence on sex-specific associations of education with neuropathology and cognition is limited. OBJECTIVE To test sex differences in education associations with neuropathologic burden and cognition. DESIGN Cohort study of data collected from September 2005 through August 2024. SETTING Multicenter autopsy cohort from the National Alzheimer’s Coordinating Center. PARTICIPANTS Adults aged 55 years or older; cross-sectional eligibility required a final CDR-SB assessment within 2 years before death, and longitudinal eligibility additionally required at least 3 assessments. EXPOSURES Years of formal education. MAIN OUTCOMES AND MEASURES Neuropathologic measures and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB). Linear regression and mixed-effects models tested associations and interactions of education with sex, neuropathology, and linear and quadratic time. Benjamini-Hochberg correction addressed multiple comparisons. RESULTS Among 2592 participants (mean [SD] age at death, 81.6 [10.8] years; 1188 [45.8%] female), 1969 contributed to longitudinal analyses. In female participants, higher education was associated with lower Thal amyloid phase, diffuse plaques, neuritic plaques, and Braak stage (β range, −0.097 to −0.071; q FDR