Effect of sex on trajectories of verbal learning and memory and clinical symptoms in diverse Alzheimer's disease cohorts

Background Women continue to demonstrate a verbal learning and memory advantage compared to men even in the earliest stages of Alzheimer's disease (AD). However, the literature on sex differences in longitudinal AD trajectories is sparse, particularly in ethnically diverse samples. Objective To examine sex differences in verbal learning and memory, as well as clinical symptoms, in clinically normal non-Hispanic white (NHW) and Hispanic/Latino (HL) cohorts longitudinally. Methods We examined longitudinal sex effects on verbal learning and memory (Spanish-English Verbal Learning Test) and clinical symptoms (Clinical Dementia Rating Scale-Sum of Boxes) in NHW (n = 529) and HL (n = 439) participants with available AD biomarkers (plasma Aβ 42 /Aβ 40 and hippocampal volume) who were clinically normal at baseline and completed follow-up assessment 18–24 months later. Results In both cohorts, women demonstrated higher verbal learning and memory scores at baseline (ps < 0.001). In the NHW cohort, longitudinal sex differences were observed in verbal learning and memory, with women maintaining performance over time, whereas men's performance declined (p = 0.071 and p = 0.020, respectively). In the HL cohort, longitudinal sex differences were observed in clinical symptoms, with men demonstrating greater decline than women (p = 0.033). Trajectories of decline did not significantly differ between ethnic cohorts. AD biomarkers did not moderate observed effects. Conclusions This study highlights the potential impact of ethnicity on sex-based differences in cognitive decline in older adulthood. Future work is needed to determine best practices for tracking progression along the AD continuum, particularly within the preclinical phase.