Parkinson's Disease 101: Environment and Lifestyle
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For the last two months I wrote about Parkinson’s in an effort to raise awareness and money for this devastating neurodegenerative disease. I recently walked in this year’s Parkinson’s Foundation Moving Day fundraiser, but it’s still not too late to show your support. Please support me by clicking the button below to donate by May 16, 2025!
The Series So Far
In case you are just joining us, here are the links to the previous posts. They are meant to be read in order, starting with the first one:
The Goal
Last year I published a scientific paper in the journal Brain that investigated Parkinson’s disease. What started out as a “bite sized” project for my postdoctoral fellowship turned into a collaborative and amazing learning experience. I learned so much during this process, and I want to impart some of this knowledge onto you! Scientific papers can be so full of jargon and technical terminology, making them a little intimidating to read. Therefore, my goal is to break down this paper into digestible short posts to take away the most important information.
If you are feeling brave, you can read the original article: link here. Otherwise, let’s start with discussing the role of lifestyle and environmental risk factors for Parkinson’s.
Lifestyle and Environmental Risk Factors
My last two posts have focused on the role genetics plays in modifying our risk of Parkinson’s. However, genetics is just one piece of the puzzle. Your lifestyle and environment also play a role!
One of the main environmental risk factors for Parkinson’s disease is toxin exposure.1 This can come from many different types of toxins, such as pesticides, solvents, and pollution.
Certain lifestyle behaviors or events can also affect your risk of Parkinson’s. For example, regular caffeine (think coffee/espresso drinks) or nicotine use (like smoking) has been associated with a lower risk of developing Parkinson’s. In other words, smoking and drinking coffee are protective of Parkinson’s disease; however, smoking to reduce your risk of Parkinson’s is never recommended; the mechanisms underlying this association are still being studied! Traumatic brain injuries (TBIs) are another example of a life event that increases one’s risk of Parkinson’s. And by TBIs, I mean concussion(s) and injuries where you hit your head hard enough to lose consciousness.
How do these lifestyle factors compare to well-established genetic risk factors, such as the LRRK2 G2019S variant, in their relationship with Parkinson’s disease? This is one of the questions we sought to address in the paper at hand.
Before we dive in, let us define the main outcome of interest. Disease penetrance is the proportion of individuals with a particular genetic mutation who actually exhibit clinical symptoms of the disease. A genetic variant is said to be highly penetrant if a high proportion of individuals carrying that genetic mutation end up developing the disease. For example, Huntington’s disease is caused by a repeating of 3 DNA letters (CAG) in the huntingtin (HTT) gene on chromosome 4. An individual will develop Huntington’s disease if they carry at least 40 CAG repeats. Put differently, Huntington’s disease is fully penetrant at 40 CAG repeats. In contrast, LRRK2 G2019S is not fully penetrant, meaning not everyone that carries the variant will develop Parkinson’s disease.
In our study, we examined how lifestyle and environmental factors may affect Parkinson’s disease penetrance. While penetrance is typically a yes/no concept, in this study we used age at diagnosis as a way to examine factors that might accelerate or delay disease expression. The environmental/lifestyle factors included 1) history of TBI with loss of consciousness, 2) non-smoking, 3) non-use of caffeine, and 4) occupational toxin exposure. We also adjusted for the participants genetic sex and education. Given the study’s focus on LRRK2 G2019S, we included carrier status into the statistical model.
If you were to rank these lifestyle/environmental factors in order of most to least associated with Parkinson’s disease penetrance, what would they be?
What we found
In our sample of 80k+ participants, including both LRRK2 G2019S carriers and non-carriers with and without Parkinson’s disease, we found that LRRK2 G2019S carrier status was the largest accelerator of time-to-Parkinson’s diagnosis with carriers having a 28% earlier age of PD diagnosis relative to non-carriers.2 Occupational toxin exposure3 was the next largest factor, accelerating time-to-Parkinson’s diagnosis by 11%. Not regularly using caffeine or nicotine accelerated time-to-Parkinson’s diagnosis by 6% and 5%, respectively. Finally, TBIs with loss of consciousness were associated with a 3% earlier age of Parkinson’s diagnosis.
What did we learn from these results? Although not fully penetrant, LRRK2 G2019S certainly had the largest effect on the penetrance of Parkinson’s disease in our cohort. After adjusting for this, occupational toxin exposure was the second largest accelerator of Parkinson’s disease, followed by non-use of caffeine, non-smoking, and TBIs with loss of consciousness. Monogenic variants of Parkinson’s disease can have a large role; however, these are quite rare in the population. Potentially modifiable lifestyle factors should also seriously be taken into account, such as wearing protective head equipment when in hazardous conditions (e.g., wearing a helmet when riding a bike or skiing) and mitigating exposure to environmental toxins (e.g., pesticides, solvents, etc.).
You may be wondering about the role of diet and exercise and their role in Parkinson’s disease penetrance. Given this study’s emphasis on lifetime exposure, diet and exercise across one’s lifetime is difficult to measure and was not included in this analysis and therefore not covered here. I encourage those interested to read the book mentioned in the first footnote for an excellent overview of these and related topics discussed here.
Summary
Monogenic forms of Parkinson’s disease, such as LRRK2 G2019S, can play a large role in disease penetrance; however, these variants are rare. Our environment and lifestyle also play factors, with occupational toxin exposure increasing Parkinson’s disease penetrance with age.
For the last two months I wrote about Parkinson’s in an effort to raise awareness and money for this devastating neurodegenerative disease. I recently walked in this year’s Parkinson’s Foundation Moving Day fundraiser, but it’s still not too late to show your support. Please support me by clicking the button below to donate by May 16, 2025!
For a nice comprehensive overview of the relationship between environmental toxin exposure and Parkinson’s disease, see the book Ending Parkinson's Disease: A Prescription for Action by Ray Dorsey MD, Todd Sherer PhD, Michael S. Okun MD, & Bastiaan R. Bloem MD PhD.
The analysis used here was a Weibull accelerated failure time model with exponentiated coefficients representing time ratios (i.e., time-to-event occurs sooner if TR < 1).
Individuals reporting occupational toxin exposure had regular exposure to pesticides at work.
Excited to follow your future work, Matt. Always great to run into a scientist!
I appreciate how you have outlined the interplay between genetic risk, environmental toxins, and lifestyle in Parkinson’s, which is something we encounter consistently in both research and lived experience. From my perspective, it’s now clear the gut-brain axis and the state of the microbiome must be added into this conversation, especially given how environmental exposures like pesticides and heavy metals not only increase risk, but actively shape the microbiome’s influence on inflammation and neurodegeneration.