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

Clinical Snapshot

Key Findings

• P Value: All p for trend >0.05 across pollutant tertiles

• Effect Size: Hazard ratios per SD: PM10 1.03, PM2.5 1.00, NOX 1.01, NO2 1.00

• Primary Outcome: No association between any air pollutant and ALS incidence

• Nnt Or Sensitivity: 687 incident ALS cases over 8.4 years median follow-up providing 80% power to detect HR ≥1.15

• Confidence Interval: All 95% CIs crossed 1.0 (e.g., PM2.5: 0.88-1.14)

Clinical Application

Results inform environmental health policy and patient counselling about ALS risk factors Relevant to Australian neurologists and environmental health specialists, though Australian air quality patterns may differ from UK. Findings support focus on established ALS risk factors rather than air pollution concerns Middle-aged to older adults in developed countries with similar air quality profiles

Abstract

BACKGROUND AND OBJECTIVES: 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. METHODS: 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 (NOX), fine particulate matter (PM2.5; <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 C9orf72 status and UNC13A genotype. RESULTS: 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, PM2.5, NOX, 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 (p for trend >0.05). Restricted cubic spline analyses revealed no nonlinear associations between air pollution and ALS risk (all p for nonlinearity >0.05). These results remained robust in various subgroup and sensitivity analyses. No evidence of gene-environment interaction was found. DISCUSSION: In this large population-based study with high statistical power, ambient air pollution was not a risk factor for the development of ALS.

References

1. 1.Chalitsios, C. V., Rudolf, O., Gao, J., Turner, M. R., & Thompson, A. G. (2026). Long-Term Exposure to Ambient Air Pollution and Incident Amyotrophic Lateral Sclerosis: A Prospective Cohort Analysis of the UK Biobank. Neurology. https://doi.org/10.1212/WNL.0000000000214858