Long-term exposure to ambient air pollution, APOE-ε4 status, and cognitive decline in a cohort of older adults in northern Manhattan

Background: There is mounting evidence that long-term exposure to air pollution is related to accelerated cognitive decline in aging populations. Factors that influence individual susceptibility remain largely unknown, but may involve the apolipoprotein E genotype E4 (APOE-epsilon 4) allele. Objectives: We assessed whether the association between long-term exposure to ambient air pollution and cognitive decline differed by APOE-epsilon 4 status and cognitive risk factors. Methods: The Washington Heights Inwood Community Aging Project (WHICAP) is a prospective study of aging and dementia. Neuropsychological testing and medical examinations occur every 18-24 months. We used mixed-effects models to evaluate whether the association between markers of ambient air pollution (nitrogen dioxide [NO2]), fine [PM2.5], and coarse [PM10] particulate matter) and the rate of decline in global and domain-specific cognition differed across strata defined by APOE-epsilon 4 genotypes and cognitive risk factors, adjusting for socio-demographic factors and temporal trends. Results: Among 4821 participants with an average of 6 years follow-up, higher concentrations of ambient air pollution were associated with more rapid cognitive decline. This association was more pronounced among APOE-E4 carriers (p < 0.001). A one interquartile range increase in NO2 was associated with an additional decline of 0.09 standard deviations (SD) (95%CI -0.1, -0.06) in global cognition across biennial visits among APOE-epsilon 4 positive individuals and a 0.07 SD (95%CI -0.09, -0.05) decline among APOE-epsilon 4 negative individuals. Results for PM2.5, PM2.5, and cognitive domains were similar. The association between air pollutants and rate of cognitive decline also varied across strata of race-ethnicity with the association strongest among White non-Hispanic participants. Conclusions: These results add to the body of evidence on the adverse impact of ambient air pollution on cognitive aging and brain health and provide new insights into the genetic and behavioral factors that may impact individual susceptibility.