Researchers have known for decades that PD risk is especially influenced by environmental factors. However, it isn’t always clear what these “environmental factors” are. Most of us have heard that pesticides are associated with PD risk, but which pesticides, when and where they are used, and their relative risk for neurodegeneration is a much more complex issue. In short, there are many environmental risk factors for PD, well beyond pesticides. And to really understand what environmental factors contribute to PD risk, we have to consider not only each of these factors individually, but the combination of exposures over a lifetime that may ultimately drive disease risk and the mechanisms by which we can intervene.

Pathogens
The first documented exogenous risk factor linked to Parkinson’s was during the 1918 H1N1 Spanish Influenza pandemic, when physicians observed an increase in PD cases between 1917 and 1918, that appeared to coincide with complications of influenza. Though subsequent analyses have questioned this link, other viral and bacterial infections are implicated in Parkinson’s risk, including evidence that opportunistic pathogens within the gut microbiome may influence PD risk.

Heavy metals
In the 1950s, case reports of manganese poisoning from occupational exposure (usually in welders) were published, describing neurologic symptoms that included motor and gait disturbances. Chronic and irreversible, manganism, the permanent neurologic disorder caused by manganese exposure, mirrors many Parkinson’s symptoms and results from degeneration of the basal ganglia. Manganese and other heavy metals implicated in PD risk, such as lead, remain relevant environmental concerns around the world today.

Pesticides
In the 1980s, the first epidemiological studies focused on PD risk from geolocation indicated that certain rural populations were at higher risk for PD, especially in Western nations. These studies suggested that an environmental factor associated with rural living, such as well water consumption or pesticide exposure was linked to PD risk. Since these pivotal studies, numerous pesticides have been since implicated in PD risk, such as organophosphates, organochlorines like dieldrin and heptachlor, fungicides like maneb, organic pesticides like rotenone, and the broad-spectrum herbicide paraquat. While many pesticides have been phased out due to their acute toxicity, paraquat is still widely used in the United States, despite strong data showing its link to PD risk.

Solvents
Chlorinated solvents are some of the most widely used chemicals in the world as convenient mechanisms to degrease in industrial settings, as dry-cleaning chemicals, paint thinners, and as chemical feedstocks for refrigerants. One chlorinated solvent of particular interest for PD risk is trichloroethylene (TCE), which was once used as an inhaled anesthetic, and is a pervasive environmental contaminant in our groundwater and soil.

Air pollution
Polluted air is a complex and dynamic mixture of numerous components, many of which are individually implicated in PD risk, such as particulate matter less than 2.5 microns (PM2.5) or the toxic gas sulfur dioxide (SO2). Though most of us are exposed to air pollution in some form, epidemiological studies suggest that certain populations with very poor air quality may be at higher risk for neurodegenerative diseases like Alzheimer’s and Parkinson’s. In addition, experimental studies suggest that particulate matter is toxic to dopaminergic neurons and may also induce an inflammatory response that could drive PD pathology.

Forever chemicals
Many industrial byproducts are still too new to fully understand their impact on neurologic disease, especially those that take decades to develop like PD. One class of chemicals of concern are perfluoroalkyl substances or PFAS, which have been used in nonstick coatings, flame retardants, carpets and clothes, and in electronics. Because of their widespread use, they now pollute much of the world and are found in nearly all humans and animals. Very early data suggests some PFAS exposures could influence PD risk, however, much more data will be needed to confirm this link.

The exposome
No one is exposed to just a single risk factor at a given time, therefore the idea of our “exposome” or the totality of our exposures and our biological responses to them is an important concept for environmentally influenced diseases such as PD. As we live in an increasingly industrial world, we have to move beyond studying single PD risk factors and understand how these factors interact to ultimately cause disease. Assessing PD from an exposome wide perspective can help achieve this, and may allow researchers to connect missing links from investigating environmental factors in isolation.

As described, there are numerous environmental risk factors implicated in PD – some more strongly linked and better studied than others. While avoiding all of these environmental factors is impossible, we are safer when we understand our risks and take action to mitigate them. Some of this must be controlled at a policy or governmental level, such as the regulations on polluting corporations or large-scale cleanup efforts. However, there are steps we can take in our daily lives to limit exposure, like filtering our water, monitoring our indoor air quality, and consuming a healthy diet. Continuing to research these risk factors for PD is an important component of understanding this disease, and hopefully, provide a way to help prevent Parkinson’s.

Briana R. De Miranda, PhD, is an Assistant Professor at the Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology at University of Alabama at Birmingham. Dr. De Miranda will be speaking at the WPC 2023 in Barcelona on the topic of “Chemical toxicant contribution to PD”. View the Scientific Program here.

Ideas and opinions expressed in this post reflect that of the author(s) solely. They do not necessarily reflect the opinions of the World Parkinson Coalition®