Child maltreatment, adult partner violence, and young onset dementia: A sequential causal mediation analysis in the UK Biobank

Background
Child maltreatment (CM) and adult partner violence correlate with late-onset dementia and mid-life risk factors. Yet we know little about whether or how they may relate to age at diagnosis and young-onset dementia (YOD) risk. We examined whether CM and adult partner violence are associated with younger age at dementia diagnosis and YOD risk, and assessed indirect pathways through adult partner violence and established YOD risk factors.

Methods
Among 147,938 UK Biobank participants with Mental Health Questionnaire and Apolipoprotein E ε4 genotype data, we identified Alzheimer’s-related, vascular, and frontotemporal dementia cases. We defined YOD as diagnosis at age ≤68 years. We examined associations between CM, adult partner violence, age at diagnosis, and YOD. We estimated time from age 18 to dementia diagnosis using Weibull accelerated failure time models across four exposure groups (CM only, adult partner violence only, both exposures, neither). We fit single-mediator causal mediation models for adult partner violence and 22 behavioural, biomedical, and environmental dementia risk factors. Sequential mediation models then estimated direct and indirect effects along a hypothesised pathway from CM to partner violence, socioeconomic deprivation, excessive alcohol consumption, and body mass index.

Results
Among 915 cases, 128 were YOD. Participants exposed to CM and partner violence received a dementia diagnosis younger than unexposed participants. In sequential causal mediation models, CM was associated with increased YOD risk (adjusted OR: 1.51; 95% CI: 1.01, 2.29) indirectly through four mediators: Adult partner violence, socioeconomic deprivation, excessive alcohol consumption, and BMI ≥30 kg/m² cumulatively mediated 78.2% of the CM–YOD association.

Conclusions
CM and adult partner violence may function as antecedents of younger dementia diagnosis and YOD risk. Violence prevention, and reducing mid-life socioeconomic deprivation, excessive alcohol consumption, and obesity among violence survivors, may help delay dementia onset and reduce YOD risk.