Mediation of the relationship between air pollution and dementia: A UK Biobank study.

BackgroundAir pollution is a potentially modifiable risk factor for dementia with a population attributable risk fraction of 3%. Little is known about the causal mechanisms behind the association, so we aimed to investigate this. MethodsData from the UK Biobank were used to investigate the association between six measures of air pollution (NO2, NOx, PM2{middle dot}5-10, PM2{middle dot}5, PM2{middle dot}5 absorbance and PM10) and dementia incidence. Indirect pathways through four mediators (cardiovascular conditions, mental health treatment, insufficient exercise and social isolation) were explored. Logistic regression was used to model the associations between air pollution, mediators and dementia. Casual mediation analysis implemented using the g-formula was used to investigate the joint indirect effect through the mediators. FindingsExposure to the highest quintile of PM2{middle dot}5 (Rte:1{middle dot}14, 95% CI:1{middle dot}06-1{middle dot}23), NOx (Rte:1{middle dot}11, 95% CI:1{middle dot}03-1{middle dot}20) or NO2 (Rte:1{middle dot}08, 95% CI:0{middle dot}99-1{middle dot}16), compared to the lowest quintile, was associated with higher dementia risk. Most of the observed association resulted from the direct effect of air pollution, consisting of pathways not captured through considered mediators. Amongst those in the highest PM2{middle dot}5 quintile, jointly intervening on the four mediators would result in a 1% reduction in risk of dementia (Rpnie:1{middle dot}01, 95% CI: 1{middle dot}01-1{middle dot}02). The randomised pure natural indirect effect was similar for NO2 (Rpnie:1{middle dot}01, 95% CI: 1{middle dot}00-1{middle dot}01) and NOx (Rpnie:1{middle dot}01, 95% CI: 1{middle dot}01-1{middle dot}02). InterpretationMost of the association between dementia and PM2{middle dot}5, NO2 and NOx occurs through the direct effect of air pollution, or other unmeasured mediators, and not pathways through these four mediators. FundingMedical Research Council (Grant MR/W006774/1).