Life-Course Psychosocial Stress and Risk of Dementia and Stroke in Middle-Aged and Older Adults

Importance: The associations of adverse childhood experiences (ACEs) and adverse adulthood experiences (AAEs) with incident dementia and stroke in the Chinese population are not well understood. Objectives: To investigate the associations of ACEs and AAEs with dementia and stroke incidence, and to examine whether depression mediates these associations. Design, Setting, and Participants: This population-based cohort study utilized data from the China Health and Retirement Longitudinal Study (June 2015 to December 2020). Participants aged 45 years and older with complete adverse experience data were included and were followed up for a mean (SD) of 4.89 (0.48) years for dementia and 4.84 (0.57) years for stroke. Statistical analysis was performed from August 20, 2025, to November 23, 2025. Exposures: ACEs and AAEs were assessed through a structured questionnaire, with cumulative scores calculated for both categories. Main Outcomes and Measures: Dementia was identified using a standardized cognitive battery and activities of daily living scale, while stroke was determined through self-reported physician diagnosis. Depression was evaluated using the 10-item Centre for Epidemiologic Studies Depression Scale. Cox proportional hazards regression analysis was used to explore the association of ACEs and AAEs with the risk of new-onset dementia and stroke, with results presented as hazard ratios (HRs) with 95% CIs. Results: Among 11 601 participants (mean [SD] age, 59.18 [9.41] years; 5569 male [48.0%]), 9145 (78.8%) were exposed to at least 1 ACE indicator, 4241 (36.6%) to at least 1 AAE indicator, and 3531 (30.4%) to both ACE and AAE markers. Both ACEs (HR, 1.11; 95% CI, 1.05-1.18) and AAEs (HR, 1.23; 95% CI, 1.14-1.33) were significantly associated with higher hazards of dementia during follow-up, whereas only AAEs were associated with higher hazards of stroke (HR, 1.19; 95% CI, 1.12-1.26). Latent class analysis identified a high-risk ACEs subgroup associated with incident stroke (HR, 1.33; 95% CI, 1.08-1.65). In the joint effects analyses, participants in the high-risk groups for both ACEs and AAEs exhibited higher hazards of dementia (HR, 3.28; 95% CI, 1.54-7.02) and stroke (HR, 2.50; 95% CI, 1.24-5.30). Depression mediated 34.3% of the association of ACEs with dementia (β = 0.10; 95% CI, 0.04-0.17), 20.9% of the association of AAEs with dementia (β = 0.22; 95% CI, 0.13-0.30), and 17.5% of the association of AAEs with stroke (β = 0.18; 95% CI, 0.11-0.24). Conclusions and Relevance: In this cohort study, exposure to adverse experiences throughout life was associated with increased risks of dementia and stroke, with depression mediating these associations. These findings highlight the importance of implementing life-course interventions that address both psychological trauma and mental health to reduce the burden of neurovascular diseases.