The mediating role of life course cognitive reserve-enhancing factors in the relationship between adverse childhood experiences and dementia among older adults: evidence from a prospective cohort study in the United States

Purpose: To explore the relationship between adverse childhood experiences (ACEs) and incident dementia, and examine the mediating effect of cognitive reserve-enhancing factors from life course perspective. Further, we verified the heterogeneities of associations of ACEs, enhancing factors, and dementia by dementia genetic risk.

Methods: Data was from the US Health and Retirement Study, involving 51,327 observations (50+) with a 10-year follow-up. Dementia was determined by the modified Telephone Interview for Cognitive Status. Six ACEs were assessed from two dimensions namely financial adversity and childhood trauma. Cognitive reserve-enhancing factors were rated during three periods of life-course, namely early-life stage (educational attainment,), adulthood (household income) and late-life stage (weekly physical activity). Genetic risk was evaluated by polygenic risk score for Alzheimer's disease. Cox regression models were conducted to examine the association between ACEs and dementia risk where ACEs were deemed as a continuous variable. "Mediation" package in R was used to test the mediating effect. Subgroup analysis was conducted to verify the heterogeneity of dementia genetic risk.

Results: Participants with one additional number of ACEs was associated with increased risk of dementia (HR = 1.08, 95% CI: 1.02, 1.16). The correlation of the number of ACEs and dementia was fully mediated by early-life stage enhancing factor and partially mediated by adulthood enhancing factor. The above mediating roles only exist among those with moderate and high dementia genetic risk.

Conclusion: Exposure to a larger number of ACEs is significantly linked to dementia, and cognitive reserve-enhancing factors might mediate this association. Early interventions on the adverse life condition and emphasis on older adults with moderate and high genetic dementia risk were recommended.