Air pollutants and amyotrophic lateral sclerosis in a population-based registry: investigating disease susceptibility, progression and survival.

Objective

to investigate the association between long-term exposure to fine particulate matter (PM2.5) and nitrogen oxides (NOx) with ALS risk, progression, and survival.

Methods

We conducted a population-based study in Lombardy, Italy. A case-control analysis included 161 incident ALS cases (2011-2014) and 161 age-, sex-, and province-matched controls. Average residential exposures to PM2.5 and NOx over the 20 years before diagnosis were estimated using European Monitoring and Evaluation Programme data and analysed with conditional logistic regression. A retrospective cohort of 135 ALS cases was used to assess associations with disease progression (ΔFS) and mortality using logistic and Cox regression models, adjusting for demographic and lifestyle factors.

Results

Higher PM2.5 exposure in the 20 years preceding diagnosis was associated with increased ALS risk (adjusted OR per 5 µg/m³ increase 1.19; 95% CI 1.01-1.40), with consistent findings across sensitivity analyses. NOx was not associated with ALS incidence. In contrast, NOx exposure in the 5 years before diagnosis was marginally associated with increased mortality (adjusted HR 1.12; 95% CI 1.00-1.26), whereas PM2.5 was not. Neither pollutant was significantly associated with disease progression rate.

Conclusions

Long-term PM2.5 exposure was associated with higher ALS risk, while NOx showed a modest association with mortality. These findings support a role of air pollution in ALS susceptibility and highlight the need for integrated environmental prevention strategies to mitigate the burden of neurodegenerative diseases.