Association of long-term outdoor air pollution exposure with incidence of Parkinson’s disease, multiple sclerosis and motor neuron diseases: a systematic review and meta-analysis

Abstract Background Parkinson’s disease (PD), multiple sclerosis (MS) and motor neurone disease (MND) are progressive and debilitating diseases that are increasing in prevalence globally. Some primary studies show an increased risk from long-term outdoor air pollution exposure, while others contradict this association. Methods As per Khreis et al. 1 protocol, a systematic review and meta-analysis was undertaken to assess the associations of long-term ( > 1 year) outdoor air pollution exposure with PD, MS and MND incidence. We searched eight databases for publications up to October 2023. Primary case-control, cohort, cross-sectional or ecological studies investigating the association of long-term air pollution and adult (>18 years old) PD, MS, or MND incidence were included. Meta-analyses were carried out using random-effects models with assessment of heterogeneity and meta-bias. PROSPERO (CRD42023417961). Results Of 31 papers included, 22 and 3 were meta-analysed for PD and MS outcomes, respectively. Most studies were from North America (14) followed by Europe (8), and Asia (6). For every 5 μg/m 3 increase of Particulate Matter 2.5 (PM 2.5 ) concentration, there was a higher PD risk (1.06; 95%CI: 1.00-1.12), but this was not true for all study settings (Prediction Interval: 0.95-1.19). This risk was largest in Asia (1.16, 95%CI:0.96-1.41). There was no evidence that PM 2.5 or nitrogen dioxide (NO 2 ) were associated with increased risk of MS. Conclusion This systematic review reports an increased risk of PD from long-term PM 2.5 exposure. The neurodegenerative diseases investigated here are rare and therefore alternatives to insufficiently powered cohort studies are needed to strengthen the evidence on risk.