Differential effects of sex/gender on brain structure in diverse Alzheimer's disease cohorts

Abstract INTRODUCTION Women show time‐limited advantages in verbal learning/memory and brain structure (hippocampal volume [HCV], cortical thickness [CT]) despite early pathology, in predominantly non‐Hispanic white (NHW) samples. METHODS We examined sex/gender effects on verbal learning/memory and structural imaging, in the context of plasma amyloid beta (Aβ42/Aβ40) and clinical diagnosis (cognitively normal [CN] or mild cognitive impairment [MCI]) in three cohorts: NHW, n = 702; Black/African American (BA), n = 244; and Hispanic/Latino (HL), n = 625. RESULTS CN NHW women and BA men showed HCV robust to amyloid ( p s < 0.043). CN BA women showed robust left precuneus and left inferior parietal CT, and CN HL men showed preserved right, middle, and left superior temporal CT ( p s < 0.038). Women across cohorts demonstrated stronger verbal learning and memory than men; clinical diagnosis and amyloid did not moderate this effect. DISCUSSION Prior work was partially replicated. Further work must parse patterns of reserve and vulnerability by sex/gender, race, and ethnicity and seek causal factors.