# Impact of adverse childhood experiences, post-traumatic stress disorder, dissociative disorders, and depression on dementia risk: a prospective analysis of associations and mediation in the UK Biobank cohort

## TL;DR

This study finds that childhood trauma, PTSD, dissociative disorders, and depression are linked to higher dementia risk, with PTSD symptoms largely explaining the connection.

## Contribution

The study identifies PTSD symptoms as a major mediator between childhood adversity and dementia risk.

## Key findings

- ACEs, PTSD, dissociative disorders, and depression are all associated with increased dementia risk.
- Self-reported PTSD symptoms explain 75% of the dementia risk linked to ACEs.
- Depression partially mediates the dementia risk from PTSD and dissociative disorders.

## Abstract

Little is known about the interrelationships among adverse childhood experiences (ACEs), post-traumatic stress disorder (PTSD), dissociative disorders, depression, and dementia risk. We sought to investigate associations of ACEs, PTSD, dissociative disorders, and depression with incident dementia and explore whether these associations may be interrelated through mediation.

This prospective cohort study used population-based UK Biobank data, including 502 355 participants recruited at 22 assessment centres who completed questionnaires, an interview, and physical assessments at baseline (2006–2010). Data are linked to participants’ electronic health records from primary care, hospital admissions, and death registers through November 30, 2022, and to the results of the UK Biobank online mental health survey (2016–2017). Cox regression and g-formula-based mediation analyses were used to examine associations between self-reported ACEs, self-reported PTSD symptoms, diagnosed PTSD, dissociative disorders, depression, and dementia.

In the final sample (n = 434 215, mean (SD) age 56.58 (8.07) years), ACEs (hazard ratio (HR)1point: 1.10; 95% CI 1.02–1.20), diagnosed PTSD (HR: 2.09; 95% CI 1.38–3.18), dissociative disorders (HR: 3.96; 95% CI 2.55–6.15), depression (HR: 2.17; 95% CI 2.05–2.30), and self-reported PTSD symptoms (HR1point: 1.09; 95% CI 1.06–1.11) were associated with increased dementia risk, after adjusting for sociodemographic characteristics. Self-reported PTSD symptoms explained 75.26% (P < .001) of the excess dementia risk associated with ACEs. Depression explained 4.51% (P = .02) of the ACEs-dementia link, 8.42% (P < .001) of the diagnosed PTSD-dementia link, and 10.29% (P < .001) of the dissociative disorders-dementia link.

Individuals with ACEs, PTSD, dissociative disorders, or depression appear to be at increased risk of dementia, potentially through both shared and unique associations. However, these findings should be interpreted with caution due to potential limitations in statistical power.