Social Determinants of Health, Genetic Susceptibility, and Risk of Dementia: A Prospective Cohort Study.

INTRODUCTION

The association between social determinants of health, genetic susceptibility, and dementia risk remains unclear. This study investigates their relationship and the potential mediation by chronic conditions.

METHODS

Data from 225,598 UK Biobank participants (220,847 for genetic analyses), with an average age of 55.07 years and 51.10% female, were analyzed. The data were collected during 2006-2010 and analyzed in 2025. Social determinants of health scores were weighted, combined, and categorized, and a polygenic risk score for dementia was constructed. Associations were assessed through Cox models, with mediation and sensitivity analyses conducted.

RESULTS

Over a median follow-up of 13.5 years, 3,232 participants developed all-cause dementia; including 1,140 Alzheimer's disease; 545 vascular dementia; and 2,259 other dementias. Each 1-unit increase in the social determinants of health score was associated with a 13%, 9%, 16%, and 14% higher risk of all-cause dementia, Alzheimer's disease, vascular dementia, and other dementias, respectively. Compared with the favorable social determinants of health group, the medium and unfavorable social determinants of health groups had hazard ratios of 1.25 (95% CI=1.13, 1.37) and 1.69 (95% CI=1.53, 1.87) for all-cause dementia. Similar trends were observed for dementia subtypes. No significant interaction was found between social determinants of health and genetic susceptibility, but those with both unfavorable social determinants of health and high genetic risk had the highest dementia risk. The impact of social determinants of health on dementia was stronger in individuals aged <60 years. Diabetes, cardiovascular disease, and depression partially mediated this association, with depression accounting for the largest share (33.6%).

CONCLUSIONS

Unfavorable social determinants of health was associated with an increased dementia risk, even in low genetic risk individuals, partly through chronic conditions. Modifying unfavorable social determinants of health may help reduce dementia risk in all populations.