Mental health, biological aging, and lifestyle mediate the associations between social determinants of health and dementia.

INTRODUCTION

Social determinants of health (SDoH) encompass non-medical factors including economic stability, education, social engagement, and environmental conditions that significantly influence health outcomes. Comprehensive evaluation of weighted SDoH scores and their underlying mechanisms in dementia risk remains limited.

OBJECTIVES

To investigate longitudinal associations between SDoH and dementia risk, and explore mediating pathways through mental health, biological aging, lifestyle, and inflammation using directed acyclic graph theory.

METHODS

We constructed a weighted SDoH score encompassing seven components across four domains: economic stability, education, social contact, and environmental factors. Cox models assessed dementia risk across SDoH tertiles. Mediation analyses examined pathways through mental health, biological aging, lifestyle, and inflammatory markers. Life expectancy differences were calculated using flexible parametric survival models.

RESULTS

A total of 359,419 UK Biobank participants (mean age: 56.26 years; 52.53% female) with a median follow-up of 13.46 years were included. We found that participants with favorable SDoH levels had a lower risk of developing all-cause dementia (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.53-0.60), Alzheimer's disease (HR, 0.62; 95% CI, 0.56-0.68), and vascular dementia (HR, 0.48; 95% CI, 0.41-0.55) compared to those with unfavorable SDoH levels. SDoH emerged as the 2nd most important factor affecting dementia risk after age. The associations between SDoH and incident dementia were mediated by mental health, biological aging, and lifestyle factors. Specifically, depression, frailty, PhenoAge, and smoking mediated 24.00%, 13.60%, 6.33%, and 2.82% of the association, respectively. At age 65, participants with dementia who had favorable SDoH levels had an average life expectancy of 0.909 (95% CI 0.002-1.816) years longer than those with unfavorable SDoH levels.

CONCLUSION

Favorable SDoH levels significantly reduce dementia risk, with mental health, biological aging, and lifestyle serving as key mediating pathways, emphasizing the importance of comprehensive social interventions for dementia prevention.