Air Pollution Linked to Increased ALS Risk and Worse Outcomes

Prolonged exposure to air pollution was associated with a higher risk of motor neuron disease, a group of neurodegenerative disorders mainly involving amyotrophic lateral sclerosis (ALS), in a nested case-control study. For each IQR increase in the 10-year average level of four air pollutants -- particulate matters with a diameter of 2.5 μm or less (PM2.5), 10 μm (PM10), or 2.5-10 μm (PM 2.5-10), and nitrogen dioxide (NO2) -- the odds of incident motor neuron disease rose compared with the general population, reported Jing Wu, PhD, of the Karolinska Institute in Solna, Sweden, and co-authors. Odds ratio of a motor neuron disease diagnosis was 1.21 (95% CI 1.09-1.34) for PM2.5, 1.30 (95% CI 1.19-1.42) for PM2.5-10, 1.29 (95% CI 1.18-1.42) for PM10, and 1.20 (95% CI 1.12-1.29) for NO2 compared with population controls, Wu and co-authors wrote in JAMA Neurology. Findings were similar in a sibling comparison. Mortality and rates of invasive ventilation were greater among motor neuron disease patients who lived in areas with higher levels of PM10 or NO2. Higher levels of all particulate matters were tied to faster functional decline, notably motor and respiratory functions, after diagnosis. Most people with newly diagnosed motor neuron disease in the study had ALS. Results were similar when restricting analyses only to patients with ALS. The findings suggest air pollution might contribute to the onset of motor neuron disorders and influence disease progression. "We can see a clear association, despite the fact that levels of air pollution in Sweden are lower than in many other countries," Wu said in a statement. What triggers motor neuron disease is largely unknown. About 85-90% of motor neuron disease cases are ALS, and in 10% of ALS patients, family history suggests an autosomal dominant inheritance pattern. Approximately 2% of ALS cases, for example, are caused by the SOD1 mutation. Interactions between environmental exposures and motor neuron disease genes need to be studied, observed Holly Elser, MD, PhD, of the Hospital of the University of Pennsylvania in Philadelphia, and Jill Goslinga, MD, MPH, of the University of California San Francisco. "Prospective studies such as PREVENT ALS now systematically follow individuals with motor neuron disease-associated gene mutations before symptom onset, and the ATLAS study represents a landmark effort to prevent disease onset in presymptomatic SOD1 mutation carriers," Elser and Goslinga wrote in an accompanying editorial. "These longitudinal studies represent a novel opportunity to examine the joint implications of genetic predisposition and cumulative environmental exposure," they noted. Given the limited efficacy of available treatments, there is also "a need for research that explores potentially modifiable risk factors for progression and mortality," the editorialists added. Wu and co-authors studied 1,463 participants recently diagnosed with motor neuron disease in Sweden from 2015 to 2023, comparing them with 1,768 siblings and 7,310 age- and sex-matched population controls. The mean age of participants with motor neuron disease was 67.3 years and 55.6% of participants were men. The sample included 1,057 people with ALS, 61 people with progressive spinal muscular atrophy, 40 people with primary lateral sclerosis, and 305 people with unspecified motor neuron disease. Disease progression was assessed by ALS Functional Rating Scale-Revised scores and subscores. The researchers analyzed levels of particulate matter and nitrogen dioxide at home addresses up to 10 years before diagnosis. At different exposure windows, the average concentrations of all four air pollutants were higher among cases than controls. Inflammation and oxidative stress from air pollution may play a role in motor neuron disease, Wu and co-authors suggested. Reduced lung function also has been linked with worse ALS outcomes, they added. The study had several limitations, the researchers acknowledged. It did not account for indoor or workplace exposures. It did not differentiate the source -- traffic, industry, or wildfire -- of pollution. The researchers also did not adjust for lifestyle factors like smoking, although the smoking rate in Sweden is about 5%, the lowest in Europe.