Abstract
Introduction: Psychological stress, trauma, and post-traumatic stress disorder (PTSD) have been associated with cognitive decline and increased dementia risk. DNA methylation (DNAm)-based epigenetic clocks provide an opportunity to examine whether adverse experiences contribute to accelerated biological ageing, which may represent one pathway linking stress to later-life cognitive outcomes. This study examined the relationships between lifetime stress, Troubles-related exposures, biological ageing, and cognitive performance in older adults in Northern Ireland.Methods: Data were derived from the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA), a nationally representative study of adults aged ≥50 years. Cognitive performance was assessed using measures including the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). DNAm data were generated for 1,953 participants using the Illumina EPIC array. Associations between four stress phenotypes (lifetime stressful events, Troubles exposure, trauma, and PTSD), cognitive performance, and epigenetic age acceleration (EAA) were examined using hierarchical regression and mediation analyses.
Results: Among participants, 69.1% reported at least one stressful life event, 43.6% reported previous trauma, and 256 met criteria for current PTSD. Adult stressful events were associated with poorer cognitive performance and stronger effects than childhood-only exposures. PTSD was associated with poorer verbal memory and lower MMSE and MoCA scores, although these relationships attenuated after adjustment for health behaviours and depression. In contrast, Troubles exposure and self-reported trauma were associated with modestly better cognitive performance. Across analyses, stress-related exposures were generally associated with accelerated epigenetic ageing, particularly when assessed using second- and third-generation clocks. Mediation analyses suggested a small indirect pathway between lifetime stress and cognition through EAA; however, EAA showed little independent association with cognition after accounting for stress exposure. Collaborative analyses with international ageing studies demonstrated the value of harmonised DNAm approaches for studying social determinants of health.
Conclusions: Lifetime psychological stress was associated with poorer cognitive performance and accelerated biological ageing in later life, whereas the associations observed for Troubles-related exposures and trauma were more heterogeneous. Biological ageing and resilience explained only a small proportion of the relationship between stress and cognition, highlighting the complexity of pathways linking adversity to healthy ageing. These findings provide the first population-level evidence of the cognitive and biological ageing consequences of stress and conflict-related experiences in older adults in Northern Ireland and support future longitudinal investigation of these relationships.
| Date of Award | Dec 2026 |
|---|---|
| Original language | English |
| Awarding Institution |
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| Sponsors | Wellcome Trust Irish Clinical Academic Training (ICAT) Programme |
| Supervisor | Bernadette McGuinness (Supervisor), Frank Kee (Supervisor) & Amy Jayne McKnight (Supervisor) |
Keywords
- NICOLA
- DNA methylation
- ageing
- stress
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