Long-term exposure to low-level air pollution, genetic susceptibility and risk of dementia

Background We aimed to assess the association between low-level air pollution and the risk of dementia, and examine the modification effect by genetic susceptibility on the relationship. Methods A total of 164 447 participants who were free of dementia at baseline and aged >= 60 years were included. Annual average concentrations of particulate matter (PM) with diameters of <= 2.5 mu m (PM2.5), between 2.5 and 10 mu m (PMcoarse), PM2.5 (absorbance) and nitrogen dioxides (NO2) were evaluated using the Land Use Regression models. Cox proportional hazards regression was used to estimate the association between air pollutants and incident dementia. Results The adjusted hazard ratio (HR) of dementia for a 5-mu g/m(3) increase in NO2 was 1.09 (95% CI, 1.05-1.14); the adjusted HR of dementia for a 1-mu g/m(3) increase in PM2.5 was 1.10 (1.04-1.17). Such significant associations were present even within concentration ranges well below the present World Health Organization, US and European annual mean limit values. In addition, higher PM2.5 (absorbance), a marker closely related to motorized traffic, was associated with higher risk of dementia. We found the risk of dementia associated with a combination of air pollutants (NO2 or PM2.5) and high genetic susceptibility (APOE-epsilon 4 alleles or overall genetic susceptibility) was greater than the addition of the risk associated with each individual factor, indicating significant interactions on an additive scale (all P-interaction < 0.05). Conclusion Long-term exposure to PM2.5 or NO2, even at relatively low levels, is associated with a higher risk of dementia. Air pollution may additively interact with the genetic susceptibility on dementia risk.