Long-term exposure to common air pollutants is associated with a higher risk of developing motor neuron disease (MND), as well as faster functional decline and poorer survival after diagnosis — even at relatively low air pollution levels.

Higher residential exposure to particulate matter (PM) and nitrogen dioxide (NO₂₎ over up to a decade before diagnosis was consistently linked to MND incidence, while specific pollutants were also associated with accelerated disease progression and increased mortality or need for invasive ventilation.

The study, led by Jing Wu, PhD, with the Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden, was published online on January 20 in JAMA Neurology. 

Mixed Literature 

MND is a group of progressive neurodegenerative disorders, most commonly amyotrophic lateral sclerosis (ALS). ALS is characterized by degeneration of upper and lower motor neurons, leading to muscle weakness, paralysis, and respiratory failure.

Although genetic factors are estimated to account for a substantial proportion of the risk for MND, environmental contributors remain incompletely defined. 

Air pollution has been implicated in several neurodegenerative diseases through mechanisms such as neuroinflammation, oxidative stress, and disruption of the blood-brain barrier. However, prior studies of air pollution and MND have produced mixed results, often limited by small sample sizes, heterogeneous designs, and inconsistent exposure assessment.

To address these gaps, the researchers conducted a population-based, nested case-control study using Swedish national registers, including the Swedish MND Quality Registry, which captures about 80% of MND cases nationwide.

Participants in the main analyses included 1463 patients with newly diagnosed MND (mean age, 67 years; 56% male) and 7130 age- and sex-matched population controls. A secondary analysis compared 947 MND cases with 1768 sibling controls to help account for shared genetic and early-life factors. 

Long-term exposure to PM measuring 2.5 μm or less (PM_2.5), 2.5-10 μm (PM_2.5-10), 10 μm or less (PM₁₀), and NO₂ was estimated using validated satellite-based spatiotemporal models linked to residential addresses, allowing calculation of average exposures up to 10 years before diagnosis.

In the main population-based comparisons, higher long-term exposure to all four pollutants was associated with increased odds of MND. For each interquartile range (IQR) increase in the 10-year average level, the odds ratio of MND diagnosis was 1.21 for PM_2.5, 1.30 for PM_2.5-10, 1.29 for PM₁₀, and 1.20 for NO₂, compared with population controls. 

These associations were attenuated when patients with MND were compared with matched sibling controls, suggesting possible residual confounding by shared familial or early-life factors, the researchers noted.

Beyond disease risk, a higher level of average exposure over 10 years to PM_2.5, PM_2.5-10, and PM₁₀ was associated with higher odds of fast MND progression, as measured by the total ALS Functional Rating Scale-Revised. The odds ratios per IQR increase were 1.34, 1.31, and 1.30, respectively.

Higher prediagnostic exposure to PM₁₀ and NO₂ was also associated with a higher risk for mortality and need for invasive ventilation after MND diagnosis. The greatest mortality risk was noted during the year before diagnosis, with hazard ratios of 1.30 for PM₁₀ and 1.23 for NO₂ per IQR increase.

Public Health Impact 

The researchers said the findings support the notion that air pollution, “even at relatively low exposure levels typical of Sweden, contributes both to the risk of developing MND and to disease prognosis after MND diagnosis.”

The results, they wrote, underscore the importance of improving air quality to reduce the risk for neurodegenerative diseases and to improve outcomes of patients with these diseases.

In an accompanying editorial, Holly Elser, MD, PhD, with the University of Pennsylvania, Philadelphia, and Jill Goslinga, MD, MPH, with the University of California San Francisco, said this study has provided “compelling evidence” that long-term air pollution exposure has implications for MND incidence, progression, and survival.

They agreed with the authors that attenuation of associations in sibling analyses raises the possibility of residual confounding by shared genetic or early-life contextual factors. 

Looking ahead, Elser and Goslinga also said that there is a need to better characterize which particulate subtypes and pollution sources are most relevant; examine interactions between air pollution and genetic risk; and understand whether socially and economically marginalized populations may experience disproportionate effects.

The study had no commercial funding. Wu, Elser, and Goslinga reported no relevant disclosures.