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.