New research reveals that exposure to air pollution, especially in metropolitan areas, dramatically increases the risk of developing Parkinson's disease and leads to more severe disease progression, underscoring the urgent need for pollution control measures.
Study: Air Pollution and Parkinson Disease in a Population-Based Study. Image Credit: Chinnapong / Shutterstock
In a recent study published in the JAMA Network Open, a group of researchers evaluated the association between air pollution exposure and the risk of developing Parkinson's disease (PD), as well as its impact on clinical characteristics and outcomes in patients with PD.
Background
PD affects around 2% of people aged 70 and older, with cases expected to triple in the next 20 years. Environmental factors, genetic predisposition, and air pollution have been linked to PD risk.
Studies suggest that particulate matter (PM2.5) and ultrafine particles can cross the blood-brain barrier, causing inflammation and oxidative stress, possibly contributing to PD development.
Nitrogen dioxide (NO2), another traffic-related pollutant, has also been implicated in PD risk. Further research is needed to clarify how air pollution influences PD risk and progression, particularly in metropolitan areas, and to explore potential interventions for reducing this risk.
About the study
The present case-control study was granted an exemption from review and informed consent by the Mayo Clinic institutional reviewer board, with all participants providing Minnesota research authorization for medical record use.
The study adheres to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines. Patients with PD were identified in Olmsted County, Minnesota, using International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes within the Rochester Epidemiology Project (REP) from 1991 to 2015.
A movement disorder specialist confirmed the diagnosis and recorded the motor symptom onset.
The study also reviewed cognitive symptoms, and the methods have been previously described. Although patients were required to live in Olmsted County at diagnosis, they could have resided outside the county during the exposure window, and prior addresses were used to link exposures.
Controls were identified from the 27-county REP region and matched to patients 20:1 based on sex and age. Controls were screened for PD codes to ensure no PD development.
Patients were divided into akinetic rigid and tremor-predominant subtypes based on clinical features. The study emphasized a focused analysis on metropolitan core populations to ensure comparable exposure profiles. PM2.5 and NO2 exposure data were collected and linked to patient addresses 10 years prior to diagnosis. Missing data resulted in exclusion from the analysis.
The study's primary outcome was PD risk, with secondary outcomes focusing on PD subtypes, mortality, and dyskinesia development.
A case-control design assessed the association of PM2.5 with PD incidence, using logistic regression models adjusted for demographics and rural-urban commuting area (RUCA) designations.
Metropolitan core sensitivity analyses were conducted to ensure comparable exposure profiles.
For the cohort study, logistic regression and Cox proportional hazards regression were used to assess PD subtypes, mortality, and dyskinesia risk, with follow-up censored at the last medical encounter or death.
Results were reported using odds ratios or hazard ratios with confidence intervals, and a linear relationship was observed between PM2.5 exposure and PD risk, with some tapering at higher exposure levels. Kaplan-Meier curves highlighted differences in outcomes based on PM2.5 exposure tertiles.
Study results
Of the 450 incident cases of PD identified in Olmsted County, 9 patients (2.0%) were excluded due to missing address information, and 95 patients (21.1%) were excluded for missing PM2.5 exposure data. This resulted in 346 PD cases (76.9%) being included in the analysis, with a median age of 72 years.
The cohort was predominantly male (62.4%) and comprised various racial groups, including White (95.4%) and small percentages of other racial backgrounds.
Similarly, controls were selected and matched to the PD cases, with 4183 controls (69.6%) included for analysis after exclusions. Controls had a median age of 72 years, and a slightly lower proportion (61.2%) were male.
The majority of PD patients resided in metropolitan cores (79.5%), compared to about a third of the controls (32.7%), prompting a sensitivity analysis focusing on metropolitan areas.
The median PM2.5 exposure prior to the index date was higher for PD patients (10.07 μg/m3) compared to controls (9.44 μg/m3).
There was a significant association between PM2.5 exposure and increased PD risk, with those in the highest quintile of exposure having a 14% increased risk compared to the lowest quintile.
NO2 exposure also showed a positive association with PD risk in the top two quintiles, with a 13% increased risk in the highest quintile compared to the lowest.
A linear relationship was observed between PM2.5 exposure and PD risk, with some tapering at higher exposure levels. A more detailed analysis using a spline model revealed a 4.9% increase in PD risk per 1-μg/m3 increase in PM2.5 exposure up to 10.6 μg/m3, after which the risk increase was 1.7% per 1-μg/m3.
A further association was found between PM2.5 exposure and the development of the akinetic rigid subtype of PD, with a 36% increased risk per 1-μg/m3 increase in exposure.
In terms of patient outcomes, 259 of the 346 PD patients had died by the time of data collection, with no significant association between PM2.5 exposure and all-cause mortality, likely due to better access to medical care in the study area.
However, 54 patients (15.6%) developed dyskinesia during the course of their disease. Each 1-μg/m3 increase in PM2.5 exposure was associated with a 42% higher risk of developing dyskinesia.
A sensitivity analysis focusing on metropolitan core populations showed higher estimates of PD risk associated with PM2.5 exposure.
For instance, the highest quintile of PM2.5 exposure in metropolitan areas was associated with a 23% increased risk of PD. Similarly, the risk of dyskinesia was elevated, with a 35% greater risk per 1-μg/m3 increase in PM2.5 exposure.
Conclusions
To summarize, in this study, higher PM2.5 exposure was linked to an increased risk of developing PD, especially the akinetic-rigid subtype, with risk increasing alongside PM2.5 levels. Exposure to NO2 was similarly associated with PD risk.
Additionally, both pollutants were linked to an increased likelihood of developing dyskinesia after PD onset.
Contrary to prior research, no significant association was found between PM2.5 exposure and PD-related mortality, possibly due to the study population's access to better medical care.
These findings suggest that reducing air pollution, particularly in metropolitan areas, may reduce the risk of PD and modify disease progression, highlighting the importance of further research into specific pollution subcomponents and their neurotoxic effects.