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This study aimed to evaluate the joint effects of multiple air pollutants including PM2.5, PM10, NO2 and NOx with dementia and examined the modifying effects of genetic susceptibility.

This study included 220,963 UK Biobank participants without dementia at baseline. Weighted air pollution score reflecting the joint exposure to multiple air pollutants were constructed by cross-validation analyses, and inverse-variance weighted meta-analyses were performed to create a pooled effect. The modifying effect of genetic susceptibility on air pollution score was assessed by genetic risk score and APOE ε4 genotype.The HR (95% CI) of dementia for per interquartile range increase of air pollution score was 1.13 (1.07~1.18). Compared with the lowest quartile (Q1) of air pollution score, the HR (95% CI) of Q4 was 1.26 (1.13~1.40) (Ptrend=2.17×10 -5 ).Participants with high air pollution score and high genetic susceptibility had higher risk of dementia compared to those with low air pollution score and low genetic susceptibility.

Our study provides evidence that joint exposure to multiple air pollutants substantially increases the risk of dementia, especially among individuals with high genetic susceptibility.