Long-term air pollution and risk of amyotrophic lateral sclerosis mortality in the Women's Health Initiative cohort

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with no cure. Although the etiology of sporadic ALS is largely unknown, environmental exposures may affect ALS risk. Objective: We investigated relationships between exposure to long-term ambient particulate matter (PM) and gaseous air pollution (AP) and ALS mortality. Methods: Within the Women's Health Initiative (WHI) cohort of 161,808 postmenopausal women aged 50–79 years at baseline (1993–1998), we performed a nested case-control study of 256 ALS deaths and 2486 matched controls with emphasis on PM constituents (PM_2.5, PM₁₀, and coarse PM [PM₁₀-_2.5]) and gaseous pollutants (NO_x, NO₂, SO₂, and ozone). Time-varying AP exposures estimates were averaged 5, 7.5, and 10 years prior to ALS death using both a GIS-based spatiotemporal generalized additive mixed model and ordinary kriging (empirical and multiple imputation, MI). Conditional logistic regression was used to estimate the relative risk of ALS death. Results: In general, PM_2.5 and PM₁₀-related risks were not significantly elevated using either method. However, for PM_10-2.5, odds ratios (ORs) were >1.0 for both methods at all time periods using MI and empirical data for PM_10-2.5 (coarse) except for 5 and 7.5 years using the kriging method with covariate adjustment. Conclusion: This investigation adds to the body of information on long-term ambient AP exposure and ALS mortality. Specifically, the 2019 US Environmental Protection Agency (EPA) Integrated Science Assessment summarized the neurotoxic effects of PM_2.5, PM_10, and PM₁₀-_2.5. The conclusion was that evidence of an effect of coarse PM is suggestive but the data is presently not sufficient to infer a causal relationship. Further research on AP and ALS is warranted. As time from symptom onset to death in ALS is ∼2–4 years, earlier AP measures may also be of interest to ALS development. This is the first study of ALS and AP in postmenopausal women controlling for individual-level confounders.