Life-course Stress Exposure and Cognitive Decline in Middle-aged and Older Chinese Adults: The Role of Sex Differences and Educational Protection

Abstract Background Stressful life events (SLEs) across the life course have been associated with cognitive decline, but evidence on their cumulative impact and potential modifiers remains limited. We aimed to examine the associations between SLE exposure in childhood, adulthood, or both life stages and cognitive trajectories, and to investigate whether these associations vary by sex and level of education. Methods We used data from the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative cohort of adults aged 45 years and older. Participants with complete data on SLEs, cognitive function, and covariates were included (n=5,922). SLEs were assessed retrospectively for childhood and adulthood periods. Cognitive function was measured using a composite score (range 0–21) across three waves (2011–2015). Linear mixed-effects models were used to examine longitudinal associations, adjusting for sociodemographic factors, health behaviors, and chronic health conditions. Interaction analyses were performed to explore effect modification by sex and education. Results Of 5,922 participants, 2,428 (41.0%) reported no SLEs, 1,374 (23.2%) experienced childhood-only SLEs, 1,294 (21.8%) experienced adulthood-only SLEs, and 826 (14.0%) had cumulative SLE exposure (both childhood and adulthood). In fully adjusted longitudinal models, cumulative SLE exposure showed the strongest association with cognitive decline (β = –0.52, 95% CI –0.69 to –0.35, p<0.001), followed by childhood-only (β = –0.34, –0.48 to –0.20, p<0.001) and adulthood-only exposure (β = –0.22, –0.37 to –0.07, p<0.01). Sex significantly moderated the associations for childhood-only and cumulative exposure (interaction β = –0.21, 95% CI –0.36 to –0.05, p<0.01; interaction β = –0.25, 95% CI –0.43 to –0.07, p<0.01), with women showing greater cognitive vulnerability than men. Higher educational attainment buffered against single-period stress effects but provided only partial protection against cumulative life-course adversity. Conclusion Life-course stress exposure, particularly when cumulative, is associated with accelerated cognitive decline in Chinese middle-aged and older adults. Women show greater vulnerability to stress-related cognitive effects, whereas higher education appears to buffer against such impacts across both sexes. These findings underscore the importance of sex-sensitive, education-informed approaches to stress reduction and cognitive health promotion across the life course.