Introduction
•The 2024 Lancet Commission on Dementia Prevention, Intervention and Care identified air pollution as one of 14 potentially modifiable risk factors associated with dementia, calculating its population attributable risk fraction to be 3%.
•However, little is known about the causal mechanisms behind the association.
•Existing studies have primarily focused on the potential for cardiovascular health to mediate the association between air pollution and dementia.
Methods
•6 measures of air pollution were reported in the UK Biobank (N=432,935): NO2, NOx, PM2·5-10, PM2·5, PM2·5 absorbance and PM10.
•Four potentially modifiable mediators on the casual pathway from air pollution to dementia were identified: cardiovascular heath; mental health; social isolation and physical inactivity.
•We used logistic regression to investigate the associations between 1) Air pollution quintiles and dementia incidence; 2) Air pollution quintiles and meditators and 3) Mediators and dementia incidence.
•Interventional effects for mediation analysis were estimated using the g-formula.
Results
•We found strong evidence for an association between dementia and PM2.5, NO2 and NOx.
•PM2.5, NO2 and NOx were associated with cardiovascular and mental health. Evidence regarding associations with other mediators was mixed.
•Social isolation, cardiovascular health, mental health and physical inactivity were associated with dementia.
•We found limited evidence that cardiovascular health conditions, mental health, physical inactivity or social isolation mediate associations between PM2.5, NO2 and NOx and dementia.
•Among participants exposed to the highest quintile of air pollution, jointly intervening on these mediators was only estimated to reduce their dementia risk by around 1%.
Conclusions
•The association between air pollution and dementia is largely driven by the direct effect of air pollution or through pathways not captured by our considered mediators.
•Interventions targeting downstream risk factors may not substantially reduce the dementia risk associated with air pollution exposure.
•Public health strategies should prioritise reducing air pollution exposure, or preventing inhalation, to lower dementia incidence.
