Parkinson’s disease prevalence is growing fast, and similar to some other neurological conditions, its causes are unclear.

The potential impact of chemicals that are toxic to neurons in the part of the brain affected by Parkinson’s disease has been investigated since the 1980s.

Despite this, many chemicals, particularly pesticides and herbicides that are known to pose a risk, are still used in many parts of the world.

Researchers have now identified a risk of Parkinson’s disease associated with exposure to 14 pesticides.

Parkinson’s disease is the fastest growing neurological disorder in the world at present, and the reason why is unclear.

Parkinson’s disease is characterized by loss of neurons in the substantia nigra, a part of the brain responsible for motor control.

The neurons in this part of the brain create dopamine, a neurotransmitter that is used for signalling in the brain. Loss of this signalling affects motor control, a common symptom in people with Parkinson’s disease.

There are a number of theories as to how and why Parkinson’s disease develops. One theory is that a peptide called alpha-synuclein accumulates in the substantia nigra neurons of people with Parkinson’s disease.

These accumultations are known as Lewy bodies, and they appear to damage the neurons and prevent them from creating the dopamine necessary for signalling.

Other theories include genetic inheritance and mitochondrial dysfunction, similar to some theories about Alzheimer’s disease. Another theory is that Parkinson’s disease is caused by exposure to environmental toxins, such as pesticides and herbicides.

The idea that some chemicals could damage the neurons in the substantia nigra, and lead to Parkinson’s disease has been around since the 1980s.

Now, research due to be presented at the American Academy of Neurology’s 76th Annual Meeting, in Denver, CO, held between April 13–18, 2024, outlines how three more pesticides have been linked to increased risk of Parkinson’s disease.

This research has not yet appeared in a peer-reviewed journal. The study was funded by the Michael J. Fox Foundation.

Parkinson’s risk depends on amount of pesticide exposure

Researchers from Amherst College, MA, Washington University in St Louis, MI, and Barrow Neurological Institute, AZ, analyzed data on 21,549,400 Medicare beneficiaries in the United States.

They then mapped usage of average annual pesticide application from 1992–2008, down to a county level.

They then used these data to look for an association between exposure to 65 well-documented pesticides and Parkinson’s disease risk across these areas. They also adjusted data for air pollution, rural/ urban residence, and median income.

Results showed an association between 14 pesticides and increased Parkinson’s disease risk in the Rocky Mountain and Great Plains region. Three of these were found to have the strongest relationship with increased risk: simazine, lindane, and atrazine.

People living in counties in the top decile for simazine use were found to have a 36% increased risk of Parkinson’s disease, while people living in the counties with the highest use of atrazine and lindane had a 31% and 25% increased risk of Parkinson’s disease, respectively.

The risk found was dose-dependent. All three of these pesticide are restricted in their use in the European Union and United Kingdom.

Lead author Dr. Brittany Krzyzanowski, a research assistant professor in the Neuroepidemiology Research Program of the Department of Neurology at Barrow Neurological Institute, told Medical News Today:

“This study was inspired by our previous work which found a strong association between Parkinson’s disease and cropland density in the Northern Great Plains. In our initial study, we used cropland density as a proxy for pesticide exposure. In the current study, we used data on the different kinds of pesticides to see which pesticides were driving the association between Parkinson’s disease and cropland in this region.”

Determining causation was challenging, she said, and work was being done by the team to get a more accurate picture of the impact of pesticide exposure.

“Our work adds to the existing literature by identifying other pesticides that may also increase the risk of [Parkinson’s disease] in specific regions of the U.S. Some pesticides have been banned in the past based upon evidence of negative health effects,“ she told us.

“We are conducting currently, studies using higher-resolution exposure data to inform public health policy in the future,” Dr. Krzyzanowski added.

Why it’s difficult to demonstrate pesticide use causes Parkinson’s

These findings support decades of research that has shown pesticide use has a dose-dependent effect on Parkinson’s disease risk, said Prof. Bastiaan R. Bloem, a neurologist and director of the Radboud University Medical Center of Expertise for Parkinson & Movement Disorders in Nijmegen, the Netherlands, who has written extensively on legislation surrounding pesticide and herbicide usage. Prof. Bloem was not involved in this research.

One of the challenges of regulating pesticide use to help avoid Parkinson’s disease, is that it was very difficult to determine the specific cause of an individual’s Parkinson’s disease, he said:

“Whether your Parkinson’s is caused by exposure to pesticides [is a difficult question to answer], and what makes it particularly difficult when it comes to a particular pesticide is [that exposure is] determined by what you eat, what you breathe, where you work, and people change when they leave and move house. They change jobs, they change diets.“

He wondered: “The from the University of Wageningen in the Netherlands found that of the nine European countries where they measured pesticides in the households of farmers and their neighbours, they found no less than 100 different pesticides, and what on Earth is the sum of all those small quantities, of all those pesticides?”

In a recent comment piece published in Nature Reviews Neurology, he points out that the E.U. recently extended marketing authorization for the use of glyphosate, the herbicide found in popular weed killer Roundup, for another 10 years, despite evidence from animal studies showing it affects the substantia nigra.

He argues that rather than the burden of proof of safety being on researchers, it should instead be on the companies, to prove their chemicals are safe.

Who is affected by pesticide use? 

Dr. Krzyzanowski said the people most likely to be at risk are those “actively working with these compounds as well as those living within proximity to farmland where these compounds are being applied.”

Different levels of risk were associated with application at ground level, versus, via aircraft for example, she said.

Exposure to these chemicals could be via inhalation, but they could also be ingested, warned Prof. Bloem.

“An additional concern is that these pesticides reached the food chain, for example, red wines in Dutch supermarkets. In the year 2023, contained seven different pesticides, including glyphosate. If you drink a red wine from a top supermarket, you’re drinking Roundup,” he warned.