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“Parkinson’s Disease and the Environment” – Webinar Notes

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In mid-June, the American Parkinson Disease Association (APDA) hosted a webinar on the environment’s impact on the risk of developing Parkinson’s disease (PD). The webinar featured movement disorder specialist Dr. Carlie Tanner, with the University of California San Francisco. The webinar consisted of a 15 minute presentation and a 45 minute question and answer session, where she detailed specific risk factors based on audience interest. 

Dr. Tanner started the presentation by describing the different environmental risk factors in PD.  These risk factors include chlorinated solvents, head injury, air pollution, physical activity, male sex, age, toxic exposure, and pesticides. 

Dr. Tanner emphasized that PD is a complex problem, and it takes more than just these risk factors to cause someone to have PD. It is a complex combination of genetics and environment. She explains it as “genetics loads the gun, environment pulls the trigger”. There are some genetic components and genes identified (such as the LRRK2 gene), but these alone won’t cause PD. Purely genetic PD or purely environmental PD is rare. 

The speaker focused on the pesticide paraquat, where there is stronger evidence that if you have had paraquat exposure, you have a greater risk of PD.  It is a commonly used herbicide used in the US and around the world.  As all farmers need to report pesticide use, it can be used to do research on population rates of PD in paraquat-using farmers versus farmers who do not use paraquat.

Environmental exposure leading to Parkinson’s disease can be prevented by diet, protective behaviors, and exercise.  The risk of PD associated with paraquat is reduced by high dietary intake of polyunsaturated fatty acids, such as walnuts and fatty fish.  If a person has a paraquat exposure and an unhealthy diet, they have a 4.5 greater risk of developing PD. “Protective behavior” is using personal protective equipment (PPE), such as masks, gloves, respirators when mixing or applying pesticide.  Not using PPE puts a person at a 4x greater risk of PD, whereas using PPE increases risk by 1.5.  Finally, physical activity slows PD disease progression.

For a recording of this session, please see the APDA YouTube webpage here.

See notes below on the June 16th webinar. 

Regards, 

– Joëlle Kuehn

“Parkinson’s Disease and the Environment” – Webinar Notes

Speaker: Dr. Carlie Tanner, MD, PhD, neurology professor, University of California San Francisco 

Webinar Host: American Parkinson Disease Association

Webinar Date: June 16, 2021

Summary by Joëlle Kuehn, Stanford Parkinson’s Community Outreach

Environmental risk factors for PD:

  • Chlorinated Solvents:
    • Trichlorethylene 
    • Perchloroethylene
    • TCE
  • Head injury:
    • Blasts during military service too
  • Air pollution:
    • components individually carry a risk
  • Physical inactivity
  • Male sex
  • Welding/metals:
    • Manganese fumes
  • Age
  • Toxicant exposure in military service:
    • Toxicants
    • blasts
  • Pesticides:
    • Paraquat
    • Rotenone
    • Organochlorine pesticides
    • Organophosphate pesticides
  • Polychlorinated biphenyls:
    • Used in electrical capacitance industry

Risk factors in PD:

  • These things are environmentally persistent – accumulate and are very hard to get out of the water and soil
  • Note: many people have exposures, and only some of those people actually get PD
  • Complex problem, it’s more than just these risk factors
  • PD is a complex disorder, while risk factor exposure is important, other factors are also important
  • Genetic aspects as well

PD is a complex disorder:

  • Complex combination of genetics and environment
  • “Genetics loads the gun, environment pulls the trigger” 
  • Genetic:
    • Genetic substrate – who you are, how you were born, how your body can handle these different exposures
    • If you don’t have the predisposition, you may never get PD
  • The other things that happen to you are that you go through in life that may cause you to have PD
  • Purely genetic PD is rare, and purely environmental PD is rare
  • Most PD is likely due to the combined effects of genetic predisposition and environmental exposures.  This is a hopeful finding because environment can be changed:
    • We can change our behavior
    • Can also target things we can identify genetically

Preventing PD:

  • Hope is that doctors can address risk factors and prevent people from getting PD, and slowing progression
  • Primary prevention:
    • Prevent PD pathogenesis
    • Preserve health – exercise, avoid exposure to chemicals, etc.
  • Secondary prevention:
    • Identify people at risk, and do something so that they don’t get PD, don’t manifest motor features
    • Prevent prodromal symptom onset.  Prodromal: features that come before the PD diagnosis, like loss of sense of smell, rapid eye movement (REM) sleep behavior disorder
    • Stop symptom progression
    • Prevent parkinsonism/dementia onset
  • At diagnosis of motor PD:
    • 50% neuron loss in substantia nigra
    • 80% striatal dopamine deficit 
    • Want to prevent that from getting worse
  • Tertiary prevention:
    • Prevent progression of disease: parkinsonism, dyskinesias, dementia, etc.

Paraquat:

  • Is a pesticide 
  • Has stronger evidence suggesting that if you have a paraquat exposure, you have a greater risk of PD
  • Commonly used herbicides
  • Used in over 100 crops
  • Agricultural and landscaping uses
  • Banned in the EU in 2007, but not banned in the US, so greater risk in US
  • Use in the US, and worldwide is increasing is increasing, meaning we all may have the opportunity to be exposed to Paraquat in recent time
  • Toxicity:
    • Redox activity – superoxide anions
  • Could do research on this because farmers need to report pesticide use, so could look at farmers and their families because they are the ones exposed

Can PD be prevented:

  • Diet: 
    • Possible for everyone
    • Study on paraquat and diet
    • Risk of PD associated with paraquat is reduced by high dietary intake of polyunsaturated fatty acid
      • Flax seed, soybean oil, walnuts, fatty fish     
    • Study done:
      • PD inverse associated with high dietary polyunsaturated fatty acids:
        • Especially a-linolenic acid   
      • Association of PD with paraquat is reduced with healthy diet, and association is stronger in those with low intake of a-linolenic
    • If they had paraquat exposure, and an unhealthy diet, they have a 4.5x greater risk of PD
  • Protective behaviors:
    • Using personal protective equipment (PPE):
      • Masks, gloves, respirators
    • People who use PPE when mixing/applying pesticides didn’t have as much of an increased risk for PD (1.5)
    • Those who wore no PPE had 4x the risk of having PD:
    • Wearing PPE can dramatically reduce risk
  • Exercise:
    • People who had more physical activity in PD reduced risk of PD:
      • Could be walking to public transportation, not just exercising and working out
    • Even if you have PD, if you exercise you can slow the rate of progression of PD
    • Even a 20% increase in exercise can reduce risk, 80% creates a very dramatic decrease in the number of people with PD

Question & Answer:

Question: Can an environmental exposure that occurred 30 years ago affect Parkinson’s disease risk now?

Answer: We know that there is a long period of time that occurs before the symptoms can be diagnosed for PD. We think it’s at least 10 years, there are symptoms that come before the diagnosis (REM sleep disorder, loss of smell, constipation). We’re not sure when that process begins, but 20-30 years from exposure to PD would not be unusual. I can’t say for your case that it’s for sure, but in our population studies, that’s what we see. 

Question: How should an individual person with Parkinson’s disease think about their own environmental exposures?

Answer: It’s almost impossible to look at a person and say “Your PD came from this”. We can look at whole populations, and see if your profile matches them, it can give us a general idea. Having said that, we need blood tests and more information to look at an individual. 

Question: Why are scientists reluctant to say that chemicals such as paraquat and rotenone cause Parkinson’s disease when these chemicals are used to induce Parkinson’s disease in lab animals?

Answer: Not all scientists are reluctant to say that, but there is conservatism and politics in science, people want to make sure that what they are saying makes sense. One way we try to understand this is in lab animals. You can induce PD in lab animals, but we don’t do that in people, so it’s hard to compare.

Question: What are the connections between military service and developing Parkinson’s disease?

Answer: You should go to the VA and get an environmental exam. There are environmental health doctors that can examine if there are any aspects of your military service that might be something that would qualify you for a service-related disability. There has been a lot of research into Agent Orange (Vietnam era exposure to an herbicide), and a lot of advocacy in the veterans community in the veterans community and broader community as a whole.

Question: Is Parkinson’s disease treated any differently if an environmental cause is suspected? 

Answer: Right now the answer is no, it isn’t. With PD it’s hard to know what factors people have been exposed to, so it’s hard to customize it if things aren’t certain. We’ve analyzed people’s occupations based on where they lived, and then we worked with experts who are industrial hygienists who could figure out the exposures. It’s hard to know specific details over someone’s entire life.

Question: Are there any studies that link computer use to Parkinson’s disease risk?

Answer: No I haven’t heard anything about that.

Question: What is your risk of developing Parkinson’s disease if your mother has Parkinson’s disease?

Answer: Your relationships with your genes and what is inherited from your parents. There are some genes that have a strong association with developing PD, so PD would clearly run in generations of your family, and it comes in different patterns (dominant – in every generation, etc). Genes like LRRK2 and GBA have an association to PD, but not everyone who has the genes gets PD, which is where the gene-environment interaction is important. Some genes need to be in combination with others to increase risk of PD. 

Question: Is anyone in the research community doing body burden studies on people with PD? Are there any studies looking at whether people with Parkinson’s disease have “forever chemicals” (chemicals that do not break down over time) in their bodies? 

Answer: I don’t know if there is a way to do that. There are lots of chemicals. Some are lipid soluble so they may be concentrated in the body fat stores. Others may not be consistent in the body but have triggered some kind of an action that continues and increases inflammatory stress. I’m not aware of if the technology can do that at this point. 

Question: What precautions do you (Dr. Tanner) take to minimize your risk of Parkinson’s disease?

Answer: Most of the things you can do aren’t just good in preventing PD, but are also good in general for health. As much as possible, I buy organic or grow my own, and try to buy local. There are studies that the mediterranean diet is good for people with PD, it’s high in fruits, vegetables and whole grains, and is low in animal fats. The other important thing is physical activity, aerobic physical activity, or just moving. The best exercise is the one you will do.

Question: In terms of Parkinson’s disease risk, is it better to live in an urban area with air pollution or a rural area with pesticide exposure?

Answer: There’s no real answer at this point. We don’t know in the US what the map of where people are who have PD. You need to have a map like that over decades to look for higher risks of people with PD.

Question: Parkinson’s disease has a history that is far older than industrial toxins. Could natural toxins such as fungal pathogens be responsible for Parkinson’s disease?

Answer: 1817 was the industrial revolution, and that’s when James Parkinson described PD. While it did exist before, it’s more frequent in the subsequent decades. We can’t say for sure because there were changes in medical care and recognition of disease. Genetic forms of PD would have existed prior to environmental exposures. When you read the old texts, sometimes they seem to describe tremors rather than PD, so it could be because of other things also (like syphilis) 

Question: Is the TOPAZ study open throughout the country?  Can anyone with Parkinson’s disease participate in the study no matter where they live in the US?

Answer: It’s a national study, so most people in the US would be eligible. We have a little bit of a limitation with budgets, so if you live in a place where there aren’t very many people, we may not be able to afford to send a nurse out. 

Question: A side effect of PD is constipation. Does gut heath play a role in increasing or decreasing risk of Parkinson’s disease?

Answer:  This is also related to genes, not yours, but the genes of the organisms in the microbiomes that are living in your GI tract, and how they may also metabolize things you eat and what you are exposed to. Having a healthy gut is important for reducing risk for PD, and if you do have PD, it may affect how you can metabolize nutrients in your diet, and how you take in and use PD medication.

Question: Dr. Tanner’s paraquat paper was published in 2012. Why has it taken over 10 years for people to be talking about the relationship between paraquat and Parkinson’s disease?

Answer: There is a lot of reluctance to focus on this area of research in relationship risk, it wasn’t easy to get that paper published. I think it is a lot easier to look at the individual, and a lot harder to say other things out there that may be related to some aspect of your risk of disease.

Question: Is there any evidence of a relationship between radioactive waste and Parkinson’s disease risk? (i.e. playing on a softball field later closed because of radioactive waste)

Answer: There is no definitive evidence of that to my knowledge at this point. People tried to look at it in Japan from people who had exposure to Hiroshima and Nagasaki and it wasn’t completely clear, but it was really hard to do that kind of study. There is research on exposure in military service. 

Question: Male sex increases the risk of Parkinson’s disease. Is there a difference in progression between men and women?

Answer: There is a little evidence that suggests that medication-related side effects like dyskinesias may be more common in women. Whether that’s because of your gender or if it is because women are smaller than men and are getting a “bigger” dose of levodopa is what people are trying to figure out. There’s a study going on about that it’s an active area of research. There is a bit of a suggestion that cognitive decline in PD may come sooner and happen more rapidly in men than women. 

Question: Have the countries that no longer use paraquat seen a reduction in Parkinson’s disease cases?

Answer: There are not many places where we have really good population statistics for how many people have PD, including in the US, so we have to look at little places. One of the places is in Minnesota around the Mayo Clinic in Rochester, and they’ve been recording people with PD in that county since the mid 1950’s. There’s another place in the Netherlands systematically. The most recent reports from Minnesota show an increasing number of people with PD, and in the Netherlands there are reducing levels of PD. In the Netherlands paraquat and other pesticides have been strongly regulated. 

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