Long-term PM2.5 exposure and diagnosis of amyotrophic lateral sclerosis: a population-based case-control study in Denmark

Abstract

BACKGROUND AND AIM: Evidence for an association between fine particle (PM2.5) exposure and neurodegenerative diseases is increasing. Whether PM2.5 exposure is relevant in amyotrophic lateral sclerosis (ALS) pathogenesis is still unknown. Only two epidemiological studies have evaluated long-term PM2.5 exposure effects in ALS. We aim to assess long-term PM2.5 exposure and ALS incidence and identify potential critical windows of exposure. METHODS: We leveraged data from the Danish National Patient Registry (NPR) on prospectively collected ALS cases (1989-2013). One-to-five controls per case were selected through the Danish Civil Registry, matched on sex, and year of birth. We estimated 1-, 5-, and 10-year PM2.5 average exposures at residential address, lagged one-year pre-diagnosis. We also estimated 1-year exposure averages from the date of diagnosis to 10 years pre-diagnosis. All exposures were estimated using predictions from a validated spatio-temporal model. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for the 1-, 5-, and 10- years exposures, adjusting for individual socioeconomic status, place of birth, civil status, and residence area. This analysis will be followed by a distributed lag analysis using the estimated 1-year exposure averages dating back to 10-years pre-diagnosis. RESULTS:Our analysis included data from 2,195 cases and 6,690 controls. In the preliminary analysis of the 1-, 5-, and 10-years exposure windows, we found no association between ALS diagnosis and PM2.5. The estimated ORs per 1 µg/m3 increase in PM2.5 were 1.00 (95%CI: 0.96–1.04), 0.99 (95%CI: 0.96–1.03), and 0.99 (95%CI: 0.95–1.02) for 1-, 5-, and 10-year averaged PM2.5 exposure respectively. CONCLUSIONS:Our preliminary results suggest no association between PM2.5 and ALS diagnosis. However, averaging long-term exposure decreases temporal exposure contrasts. Our lagged analysis will be important to more precisely analyze windows of exposure dating back to 10 years pre-diagnosis and crucial to verify our preliminary findings. KEYWORDS: ALS, air pollution, particle matter, windows of exposure