Joint effect of polysocial risk score, lifestyle and genetic susceptibility with the risk of dementia: A prospective cohort study.

OBJECTIVES

The comprehensive impact of polysocial risk score (PsRS)-encompassing multiple social determinants of health (SDoHs) with genetic and lifestyle factors on dementia incidence remains to be elucidated.

STUDY DESIGN

This study aimed to clear the associations between PsRS and dementia incidence and evaluated how genetic and lifestyle factors modified these associations in the UK Biobank cohort.

METHODS

The detailed prospective study involved over 500,000 participants when recruited in 2006-2010. The PsRS was calculated by 12 SDoHs across psychosocial factors, socioeconomic status, and neighborhood and living environment. A healthy lifestyle score was constructed from physical activities, alcohol consumption, smoking status, and diet. A genetic risk score (GRS) was computed via genotype data from UK Biobank. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association between PsRS, lifestyle factors, GRS and dementia.

RESULTS

Results showed the participants with intermediate (HR = 1.32, 95%CI: 1.20-1.45) and high PsRS (HR = 2.10, 95 % CI: 1.91-2.32) were significantly associated with an increased risk of dementia compared with those with a low PsRS. Then, compared with participants with low PsRS and favorable lifestyle/low GRS, high PsRS and unfavorable lifestyle/high GRS had the highest risk of dementia (HR = 3.11,95%CI: 2.63-3.68)/(HR = 3.56, 95%CI: 2.62-4.85).

CONCLUSIONS

Both high PsRS and GRS were significantly associated with higher dementia risk. A favorable lifestyle could reduce dementia incidence regardless of high PsRS or GRS. Additionally, focusing on the intervention of SDoHs would be positive in preventing dementia.