Associations of Air Pollution and Genetic Risk With Incident Dementia: A Prospective Cohort Study.

ABSTRACT

Evidence on the association between air pollution and dementia is accumulating but still inconclusive, and the potential effect modification by genetics is unclear. We investigated the joint effects of air pollution exposure and genetic risk on incident dementia in a prospective cohort study, the UK Biobank study. Land use regression models were used to estimate exposure to ambient particulate matter (PM) in 3 fraction sizes (PM with diameter < 2.5 µm (PM2.5), coarse particles (PM with diameter 2.5-10 µm (PMc)), and PM with diameter < 10 µm (PM10)), PM2.5 absorbance, nitrogen dioxide levels, and nitrogen oxide levels at each individual's baseline residence. A polygenic risk score was calculated as a quantitative measure of genetic dementia risk. Incident cases of dementia were ascertained through linkage to health administrative data sets. Among the 227,840 participants included in the analysis, 3,774 incident dementia cases (including 1,238 cases of Alzheimer disease and 563 cases of vascular dementia) were identified. After adjustment for a variety of covariates, including genetic factors, positive associations were found between exposure to air pollution-particularly PM10, PM2.5 absorbance, and nitrogen dioxide-and incident all-cause dementia and Alzheimer disease but not vascular dementia. No significant interaction between air pollution and genetics was found, either on the multiplicative scale or on the additive scale. Exposure to air pollution was associated with a higher risk of developing dementia regardless of genetic risk.