New evidence supports causal link between air pollutant, Parkinson’s
Long-term exposure to 'fine particular matter' cited in UK population study
A new population study has provided evidence of a potential causal link between exposure to an air pollutant called fine particular matter (PM2.5) and the development of Parkinson’s disease in the U.K.
Data also showed that exposure to ground-level ozone, a gas that can damage the lungs, was not causally associated with Parkinson’s.
“We found robust associations between PM2.5 exposure and [Parkinson’s disease], suggesting that there could be a causal relationship between long-term exposure to air pollution, particularly PM2.5, and incident [Parkinson’s],” the researchers wrote. Simply put, the team concluded that “PM2.5 exposure may have a causal relationship with Parkinson’s disease.”
According to the team, this study’s major strength was the application of several advanced causal analysis methods that went beyond traditional statistical modeling. This approach helped balance the impact of clinical or demographic factors on the findings, whether they were measured or not.
“From a public health perspective, our findings suggest that air pollution mitigation could be a preventive measure against the development of [Parkinson’s disease],” the researchers wrote.
Titled “Causal association between long-term exposure to air pollution and incident Parkinson’s disease,” the population study was published in the Journal of Hazardous Materials.
Researchers turn to causal modeling approaches to examine possible links
Several studies have suggested that exposure to air pollution may contribute to the development of Parkinson’s disease. Still, numerous other studies have shown no connection whatsoever.
However, nearly all of these studies are observational by design, which means the outcomes are limited to a statistical association, or correlation, between air pollution exposure and Parkinson’s risk.
Even when correcting for clinical or demographic variables — so-called confounding factors that may influence an investigation’s results — these observational studies cannot directly determine whether air pollution can cause Parkinson’s using standard statistical methods.
That is, there may be other reasons, not accounted for in these studies, that may explain the increased risk of Parkinson’s in people exposed to air pollution.
That resulting knowledge gap led a team of scientists in Australia, Canada, and China to try a new strategy: The team instead applied traditional and multiple causal modeling approaches to investigate a potential causal relationship between air pollution and Parkinson’s development.
Using data from the U.K. Biobank, the team identified 293,888 people who did not have Parkinson’s to track throughout a long-term study. At its start, or baseline, these study subjects ranged in age from 40 to 69; 54% were women.
During a median follow-up of 11.6 years, there were 1,822 new cases of Parkinson’s.
Air pollution data were derived from the EMEP4UK platform, which provides the daily concentrations of various air pollutants, including lung-damaging ozone and fine particulate matter, known as PM2.5.
PM2.5 refers to particles in the air that are less than 2.5 micrometers in diameter — about 30 times smaller than a human hair. These particles are comprised of dust, ash, soot, aerosols, and mold spores, among other substances.
Because they are fine, or minuscule, the particles can enter the body through the lungs, reach the brain from the bloodstream, and potentially trigger inflammation and damage.
New analysis methods provide evidence of potential causal link: Researchers
In the study, the individuals’ pollution exposure was based on their residence before and after recruitment, the concentrations of pollutants surrounding the residence, and the time they lived there. Also taken into account were the average levels of air pollutants in the area during the three years before the study.
Confounding factors influencing Parkinson’s risk included age, sex, body mass index, educational level, employment status, household annual income, and socioeconomic deprivation. Smoking habits, alcohol intake, physical activity, diet, history of depression, head trauma, and family history of Parkinson’s were included.
In addition, the team calculated a polygenic risk score based on genetic changes associated with Parkinson’s. Simply put, a polygenic risk score is a way to estimate a person’s genetic risk for a particular trait or disease based on variations in multiple genes across their genome.
The scientists used standard modeling, called time-varying Cox proportional-hazard regression.
Data showed an increase in exposure to 1 microgram per cubic meter (ug/m3) of PM2.5 was associated with a 23% increased risk of Parkinson’s. However, even after correcting for all confounding factors, this significant association did not necessarily mean that air pollution was a causative factor for Parkinson’s. This type of statistical method is used to analyze data considering how factors influencing the risk of an event may change over time.
The researchers then incorporated a propensity score into the Cox models to account for potential confounding factors and reduce bias. Here, there was a 19% elevated Parkinson’s risk with every 1 ug/m3 of increased PM2.5 exposure. Similar findings were found when Cox models were adjusted with inverse probability weights, a method to estimate causal associations by controlling for confounding factors.
Instrumental variable analysis was then applied to further estimate the causal link between air pollution exposure and Parkinson’s, even when unmeasured confounding factors were included.
Using this method, there was a significant 43% increased risk of Parkinson’s for every increased exposure of 1 ug/m3 PM2.5, the researchers found.
Our study provides evidence to support a causal association between PM2.5 exposure and [Parkinson’s disease].
This type of analysis is used to estimate the causal effect of a treatment or intervention when traditional methods may be biased due to confounding factors.
Finally, the team conducted a negative control outcome analysis, which evaluated any potential bias due to confounding factors that were not measured or included. The results showed no significant associations between air pollution and negative control outcomes, meaning the link between air pollution and Parkinson’s was not likely due to unmeasured confounding factors.
Altogether, “based on a large prospective cohort [study group], we found consistent associations between long-term exposure to air pollution, in particular PM 2.5, and increased risks of [Parkinson’s disease] using various causal modeling approaches,” the researchers wrote.
Across all models, there was no causal link between ozone exposure and Parkinson’s risk, the data showed.
“Our study provides evidence to support a causal association between PM2.5 exposure and [Parkinson’s disease],” the researchers concluded.
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