Associations and Mediating Pathways between Childhood Adversity and Risk of Dementia: A Cohort Study in the UK Biobank.

BACKGROUND:While childhood adversity (CA) is known to be associated with multiple adverse outcomes, its link with dementia is an area with limited exploration and inconsistent agreement. The study aimed to examine the longitudinal associations of CA with incident all-cause dementia and to quantify the potential mediating pathways. METHODS:Data from the UK Biobank. CA, encompassing neglect and abuse, was evaluated retrospectively by an online mental health questionnaire. Physical performance, psychological factors, lifestyles, and biological indicators assessed at baseline were considered potential mediators. Incident all-cause dementia was defined by International Classification of Diseases, Tenth Revision codes obtained through self-reported medical conditions, primary care, hospital admission, and death registrations. Cox proportional hazard models were applied to estimate the longitudinal associations. Mediation analyses were conducted on potential mediators to examine their contribution. RESULTS:This cohort study comprised 150,152 non-demented individuals (mean [SD] age, 55.9 [7.7] years) at baseline (2006-2010). Compared to individuals who did not experience CA, those exposed to any CA exhibited a 30.0% higher risk of dementia (hazard ratio [HR] =1.300, 95% confidence interval [CI]: 1.129-1.496). Each additional CA was associated with a 15.5% (95% CI: 8.8-22.5%, P  for trend < 0.001) increased dementia risks. Depression, smoking, and low grip strength explained 8.7%, 2.4% and 0.9% of the associations, respectively. Biomarkers involving inflammation, erythrocytes, liver, and kidney function mediated the associations by 0.6% to 1.4%. CONCLUSIONS:The study revealed the detrimental effects of CA on dementia and identified some potential mediators, namely depression, smoking, low grip strength, and several targeted biomarkers. In addition to calling more attention to CA, the findings underscore the importance of interventions targeting modifiable mediators in preventing dementia.