Long-Term Exposure to Ambient Air Pollution and Incident Amyotrophic Lateral Sclerosis: A Prospective Cohort Analysis of the UK Biobank.

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a complex etiology. Although a range of genetic and lifestyle factors have been implicated, the potential role of environmental airborne pollution exposure is uncertain. This study examined the association between long-term ambient exposure to air pollutants and the incidence of ALS in UK Biobank participants. This prospective cohort study was based on the UK Biobank participants aged 40-69 years. The analytical sample comprised participants free of ALS at baseline and had complete data on air pollution exposure. Long-term exposure (2006-2021) to nitrogen dioxide (NO₂), nitrogen oxides (NO_X), fine particulate matter (PM_2.5; <2.5 µm), and coarse particulate matter (PM₁₀; <10 µm) was assessed using data from the UK Department for Environment, Food and Rural Affairs at a spatial resolution of 1 × 1 km. To evaluate the association between these pollutants and ALS risk, we used multivariable time-varying Cox proportional hazards models. Several sensitivity analyses were conducted to assess the robustness of the results. We also examined for gene-environment interaction stratified by <i>C9orf72</i> status and <i>UNC13A</i> genotype. Among the 501,308 participants with a mean age of 56.5 (SD 8.1) years at baseline, 272,764 (54.4%) were female. Over a median follow-up of 8.4 years, 687 individuals developed ALS. We did not observe any associations for any of the examined pollutants and ALS risk. Specifically, the hazard ratios per SD increment for PM₁₀, PM_2.5, NO_X, and NO₂ were 1.03 (95% CI 0.92-1.15), 1.00 (95% CI 0.88-1.14), 1.01 (95% CI 0.90-1.13), and 1.00 (95% CI 0.89-1.12), respectively. Individuals living in areas with the highest tertile of air pollutant exposure, compared with those in the lowest tertile, did not show a higher risk of ALS across any of the pollutants examined (<i>p</i> for trend >0.05). Restricted cubic spline analyses revealed no nonlinear associations between air pollution and ALS risk (all <i>p</i> for nonlinearity >0.05). These results remained robust in various subgroup and sensitivity analyses. No evidence of gene-environment interaction was found. In this large population-based study with high statistical power, ambient air pollution was not a risk factor for the development of ALS.