Prominent role of PM10 but not of circulating inflammation in the link between air pollution and the risk of neurodegenerative disorders

BackgroundSeveral studies revealed an implication of air pollution in neurodegenerative disorders, although this link and the potential underlying mechanisms remain unclear. ObjectivesTo analyze the impact of air pollution on neurodegenerative risk by testing multiple pollutants simultaneously, along with other potential risk/protective factors, and the role of circulating inflammation. MethodsIn the Moli-sani cohort (N=24,325; [&ge;]35 years; 51.9% women, baseline 2005-2010), we estimated yearly levels of exposure to nitrogen oxides, ozone, particulate matter (PM10), sulfur dioxide and BTX hydrocarbons in 2006-2018, applying residence geo-localization of participants and Kriging interpolation algorithm to land measurements of air pollutants. We performed a principal component (PC) analysis of pollutant levels and tested associations of the resulting PC scores with the incident risk of dementia (AD) and Parkinsons disease/parkinsonism (PD), through multivariable Cox PH regressions adjusted for age, sex, education level, and several professional and lifestyle exposures. Moreover, we tested whether a composite biomarker of circulating inflammation (INFLA-score) may explain part of these associations. ResultsOver 24,308 subjects with pollution data available (51.9% women, mean age 55.8(12.0) years), we extracted three PCs explaining [&ge;]5% of pollution exposure variance: PC1 (38.2%, tagging PM10), PC2 (19.5%, O3/CO/SO2), PC3 (8.5%, NOx/BTX hydrocarbons). Over a median (IQR) follow-up of 11.2(2.0) years, we observed statistically significant associations of PC1 with an increased risk of both AD (HR[CI] = 1.06[1.04-1.08]; 218 cases) and PD (1.05[1.03-1.06]; 405 incident cases), independent on other covariates. These associations were confirmed testing average PM10 levels during follow-up time (25[19-31]% and 19[15-24]% increase of AD and PD risk, per 1 g/m3 of PM10). INFLA-score explained a negligible (<1%) proportion of these associations. DiscussionAir pollution - especially PM10 - is associated with increased neurodegenerative risk in the Italian population, independent on concurring risk factors, suggesting its reduction as a potential public health target.