Prevention And Parkinson’s Disease: From Population Studies To Precision Medicine

Introduction
James Parkinson’s 1817 description of the shaking palsy established a recognizable motor syndrome, but its cause remained uncertain for more than a century. Early explanations invoked hardship, stress, infection, and inheritance. [1] Current evidence supports a complex model in which Parkinson’s disease (PD) arises from interacting genetic susceptibility, environmental exposures, lifestyle, and other host factors. This framework creates opportunities for personalized treatment and prevention by identifying potentially modifiable factors. This historical overview highlights collaborations with Samuel Goldman, J. William Langston, Kenneth Marek and Ethan Brown.

Environmental determinants and gene-environment interaction
The 1983 description of MPTP-induced parkinsonism showed that a chemical exposure could selectively injure dopaminergic neurons and produce a syndrome resembling PD. [2] Subsequent epidemiologic studies strengthened the case for environmental contributions. Among 31,848 World War II veteran twins, PD concordance was similarly low in identical and fraternal pairs overall, and only slightly higher in identical twins with young onset, supporting an important environmental role. [3,4]

Pesticide exposure has been associated with PD in many studies, but “pesticides” is an umbrella term encompassing chemicals with different biological effects. Few studies have identified specific pesticides. In the Agricultural Health Study, paraquat or rotenone exposure was associated with approximately 2.5- to 2.8-fold higher odds of PD. [5] Increased risk has also been associated with organochlorines, permethrin, 2,4-D and other compounds.

Chlorinated solvents provide another example. Occupational trichloroethylene (TCE) exposure was associated with PD in WWII veteran twins. At Marine Corps’ Camp Lejeune, where drinking water was contaminated for decades with TCE, service members had 70% higher odds of PD than those at Camp Pendleton, where water was not similarly contaminated. [6] TCE is environmentally persistent and can volatilize from contaminated soil or groundwater into indoor air. PCBs and air pollution have also been associated with PD risk.

Yet most exposed individuals do not develop PD, underscoring the importance of susceptibility and combinations of exposures, genes, lifestyle, and other biological modifiers. Research on specific chemicals and mechanisms, combined exposures, and gene-environment interactions is needed to advance precision prevention and treatment.

A growing global challenge
The Global Burden of Disease study estimates that PD is increasing rapidly worldwide. [7] The World Health Organization identifies prevention and risk reduction, research, diagnosis and care, caregiver support, advocacy, and assessment of disease burden as priorities for global action. [8]

Prevention across the disease continuum
Prevention can be considered at three levels. Primary prevention seeks to prevent disease initiation by reducing causal or contributing exposures. Secondary prevention aims to identify biological disease early enough to delay clinical manifestations. Tertiary prevention seeks to slow progression, prevent complications, and preserve independence after diagnosis.

Progress in early detection makes secondary prevention increasingly feasible. Hyposmia, or reduced odor identification, is an informative prodromal feature. In the Honolulu Asia Aging Study, hyposmia predicted subsequent PD and, among participants not diagnosed during life, PD pathology at autopsy. [9] In the Parkinson’s Associated Risk Syndrome (PARS) study, hyposmia combined with abnormal dopamine transporter imaging identified individuals at substantially increased PD risk. [10] The Parkinson’s Precision Medicine Initiative (PPMI) has extended staged screening by integrating smell testing, REM sleep behavior disorder, genotype, dopamine transporter imaging, and assays for misfolded alpha-synuclein. [11] These approaches can identify biological disease before conventional motor diagnosis, providing a potential window for secondary prevention.

Precision medicine and emerging determinants
Historically, PD treatment and clinical trials have often used a “one size fits all” approach despite biological heterogeneity. Precision medicine seeks the right intervention for the right person at the right time by integrating genetic, environmental, lifestyle, clinical and biomarker information. Emerging areas include the microbiome, early-life exposures, infection and inflammatory state. Understanding their combined effects and shared mechanisms may improve prevention and treatment. PPMI gene-environment analyses show phenotypic differences in people with pesticide exposure and GBA or LRRK2 risk variants, illustrating why individual susceptibility matters. [12]

Tertiary prevention and practical risk reduction
For people living with PD, tertiary prevention—preventing disease consequences—is critical. Exercise and physical therapy can support mobility; attention to bone health, cognition, speech and swallowing may help avoid falls, dysphagia and loss of independence. Medical care should proactively anticipate and prevent new problems.

What can each of us do now?
We do not yet have a proven way to prevent PD. Nevertheless, several practical actions are sensible:

  • Reduce unnecessary toxicant exposure: Choose safer alternatives to pesticides and solvents when possible, and use appropriate precautions when exposure is unavoidable. Protective glove use and hygiene when using pesticides attenuated PD risk in our research. [13]

  • Know your environment: Be aware of possible air and water toxicant exposures at home and work, and take appropriate steps to minimize exposure.

  • Reduce exposure to wildfire smoke and severe air pollution: Use air filtration and protective masks when needed.

  • Stay physically active and eat a healthy diet: These habits have broad health benefits and are associated with lower PD risk. Favor a plant-rich diet low in processed food, red meat and animal fat; wash and peel produce or consider organic products.

  • Think preventively: People with PD and their loved ones can work with their care team to anticipate falls, cognitive or swallowing changes, and other threats to independence, and implement interventions.

  • Participate in research: New understanding depends on research volunteers.

  • Advocate: Sustained research support is needed to understand disease onset and progression and develop effective interventions. Advocacy is also needed for primary prevention by reducing environmental toxicants associated with disease, and for awareness, stigma reduction, health care and related services for people with PD.

Individual choices matter, but people cannot control every environment in which they live and work. Precision treatment and population-wide prevention must go together: the right intervention for the right person at the right time, while reducing preventable hazards for everyone.

More than 200 years after Parkinson’s description, our goal should be not only better treatment but preventing what we can: disease onset, disabling symptoms and loss of independence. If we can identify preventable causes, we have an opportunity—and a responsibility—to act.

Selected references

1. Parkinson J. An Essay on the Shaking Palsy. 1817.
2. Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science. 1983;219:979-980. doi:10.1126/science.6823561
3. Tanner CM, Ottman R, Goldman SM, et al. Parkinson disease in twins: an etiologic study. JAMA. 1999;281:341-346. doi:10.1001/jama.281.4.341
4. Goldman SM, Marek K, Ottman R, et al. Concordance for Parkinson’s disease in twins: a 20-year update. Ann Neurol. 2019;85:600-605. doi:10.1002/ana.25441
5. Tanner CM, Kamel F, Ross GW, et al. Rotenone, paraquat, and Parkinson’s disease. Environ Health Perspect. 2011;119:866-872. doi:10.1289/ehp.1002839
6. Goldman SM, Weaver FM, Stroupe KT, et al. Risk of Parkinson disease among service members at Marine Corps Base Camp Lejeune. JAMA Neurol. 2023;80:673-681. doi:10.1001/jamaneurol.2023.1168
7. GBD 2016 Parkinson’s Disease Collaborators. Global, regional, and national burden of Parkinson’s disease, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018;17:939-953. doi:10.1016/S1474-4422(18)30295-3
8. Schiess N, Cataldi R, Okun MS. Six action steps to address global disparities in Parkinson disease: a World Health Organization priority. JAMA Neurol. 2022;79:929-936. doi:10.1001/jamaneurol.2022.1783
9. Ross GW, Petrovitch H, Abbott RD, et al. Association of olfactory dysfunction with risk for future Parkinson’s disease. Ann Neurol. 2008;63:167-173. doi:10.1002/ana.21291
10. Jennings D, Siderowf A, Stern M, et al. Conversion to Parkinson disease in the PARS hyposmic and dopamine transporter-deficit prodromal cohort. JAMA Neurol. 2017;74:933-940. doi:10.1001/jamaneurol.2017.0985
11. Brown EG, Chahine LM, Siderowf A, et al. Staged screening identifies people with biomarkers related to neuronal alpha-synuclein disease. Ann Neurol. 2025;97:730-740. doi:10.1002/ana.27158
12. Brown EG, Goldman SM, Coffey CS, et al. Occupational pesticide exposure in Parkinson’s disease related to GBA and LRRK2 variants. J Parkinsons Dis. 2024;14:737-746. doi:10.3233/JPD-240015
13. Furlong M, Tanner CM, Goldman SM, et al. Protective glove use and hygiene habits modify the associations of specific pesticides with Parkinson’s disease. Environ Int. 2015;75:144-150. doi:10.1016/j.envint.2014.11.002

Caroline M. Tanner, MD, PhD is a neurologist in San Francisco, California and is affiliated with UCSF Health-UCSF Medical Center. She has spoken at multiple World Parkinson Congresses over the years.

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

Basic ScienceCaroline M. Tanner, MD, PhDParkinson's, Prevention, study, eleven