Neurology Minute

Dr. Margarita Fedorova discusses possible environmental exposures and their risk of Parkinson disease. 
Show citation: 
Dorsey ER, De Miranda BR, Hussain S, et al. Environmental toxicants and Parkinson's disease: recent evidence, risks, and prevention opportunities. Lancet Neurol. 2025;24(11):976-986. doi:10.1016/S1474-4422(25)00287-X 
Show transcript: 
Dr. Margarita Fedorova:
Welcome to Neurology Minute. My name is Margarita Fedorova and I'm a neurology resident at the Cleveland Clinic. Today, we're reviewing some information about possible environmental exposures and their risk of Parkinson disease. As we see in diagnose patients with Parkinson, they often want to know why they developed it and some emerging studies may offer insights. A recent personal view published in The Lancet Neurology by Ray Dorsey and colleagues in November 2025 examined associations between three environmental exposures and Parkinson's disease; pesticides, dry cleaning chemicals and air pollution. Since only five to 15% of Parkinson's cases have an identifiable genetic cause, environmental factors are an important area of investigation. Dorsey and colleagues describe studies showing that pesticide exposure is associated with Parkinson's risk.
One example is Paraquat, an herbicide widely used in agriculture. It's banned in over 30 countries, but remains legal in the United States. In a population-based US study, residents living or working near areas where Paraquat was sprayed at twice the risk of developing Parkinson's, suggesting residential proximity alone may confer risk.
Other pesticide exposures may show similar patterns. The organic chlorides, DGT and gildren are used in various agricultural areas. They're fat-soluble compounds that accumulate over decades. Postmortem studies found that when brains with lewd pathology and some studies suggest developmental exposure may increase risk of neurodegeneration years later. There have also been risks possibly associated with chemicals used in dry cleaning and metal degreasing. Trichloroethylene or TCE is one such chemical that was found in high amounts in the water at Camp Lejeune in North Carolina. A study of over 170,000 marines stationed there showed a 70% increase in risk of developing Parkinson's compared to marines at a non-contaminated base. What's particularly striking is the timing. Marines were exposed at an average age of 20 and the exposure lasted just over two years, yet disease manifested 34 years later. This suggests a long latency period between exposure and disease onset.
TCE is also concerning because it evaporates from contaminated groundwater and can seep into buildings. As of 2000, 30% of US groundwater was contaminated with TCE. The third category of environmental exposure is air pollution. Studies from Canada, South Korea, Taiwan, and the UK show association between exposure to fine particular matter known as PM 2.5 in nitrogen dioxide with increased Parkinson's risk. These pollutants come from vehicle emissions, industrial sources, and combustion processes. The studies suggest that chronic exposure to these air pollutants may contribute to neurodegeneration through inflammatory and oxidative stress mechanisms. Unlike pesticides and dry cleaning chemicals, the magnitude of increased risk is often modest, typically ranging from one to 20%. However, the potential impact at large since almost everyone worldwide, 99% of people breathe on healthy air.
For us as clinicians, this underscores the importance of taking detailed environmental histories. When patients ask, "Why me?" We can acknowledge that environmental exposures may have contributed to their disease. It's important to note that these studies show associations, but they don't confirm clear causation. Regardless, they may provide some answers to patients asking about the etiology of their Parkinson's or even the risks to others.
That's your neurology minute for today. Keep exploring and we'll see you next time. If you want to read more, please find the paper by Ray Dorsey, titled Environmental Toxicants and Parkinson's Disease: Recent Evidence and Prevention Opportunities, published online in The Lancet Neurology in November 2025.

In the second episode of this two-part series, Drs. Justin Abbatemarco, Valérie Biousse, and Nancy J. Newman discuss the risk of non-arteritic ischemic optic neuropathy and how to counsel patients around GLP-1 medications. 
Show transcript: 
Dr. Justin Abbatemarco:
Hello and welcome back. This is Justin Abbatemarco again with Valarie Biousse and Nancy Newman talking about non-arteritic ischemic optic neuropathy. I think the other major point that we had a discussion in the podcast was around the GLP-1 medications, which you mentioned have been truly life-changing for diabetes management and obesity.
Can we talk about the risk of non-arteritic ischemic optic neuropathy and how you're counseling patients around this class of medications?
Dr. Nancy J. Newman: 
Absolutely. This is probably one of the most difficult things we are dealing with because it is something that is in process and progress right now. We don't have all the information yet, but it would appear that there is likely a small association of about slightly less than two times risk in patients who are taking these medications of having NAION with a resultant still very, very small overall risk. And it is not necessarily causal.
This has prompted the European Medicines Agency to say that these patients should have their GLP-1 RAs stopped if they have NAION. Our own FDA and certainly the American Academy of Ophthalmology and the North American Neuro-Ophthalmology Society have not taken that step, but have suggested that this be shared decision-making, not only with the person who makes this diagnosis of an NAION in the patient, but with their primary care doctor or the provider who has felt that a GLP-1 receptor agonist is important for this patient's treatment and health.
Dr. Justin Abbatemarco:
More to come. We're going to have you back to have discussions as we learn more and better understand the disease and how we help our patients with both their diagnosis and treatment. Thank you so much for your time.

In part one of this two-part series, Drs. Justin Abbatemarco, Valérie Biousse, and Nancy J. Newman discuss common myths around non-arteritic ischemic optic neuropathy (NAION).
Show transcript: 
Dr. Justin Abbatemarco:
Hello and welcome. This is Justin Abbatemarco, and I just got done interviewing Valérie Biousse and Nancy Newman on all things around non-arteritic anterior ischemic optic neuropathy. I think one of my favorite takeaways from our interview were breaking some common myths around this disorder. Valérie and Nancy, could you maybe talk about one or two that you think are important that people should know are not true about this disease?
Dr. Nancy J. Newman:
So thing number one is that it's just another stroke of the eye. We know that it likely does have some vascular background to it, but the reality is it's not a stroke like neurologists know a stroke. You don't need to do an embolic workup. It has to do likely with the anatomy that a person is born with or that they acquire that crowds the front of their optic nerve. Secondly, thing number two, that it's a disease only of old people. I think that we know that you can be as young as age 11 and have this happen, mostly because you have a small, crowded optic nerve head. Thing number three, steroids really have not been proven to be helpful in this disorder and should likely not be used unless you are trying to decrease the optic nerve head edema, and the patient is insisting that they have some treatment.
Dr. Justin Abbatemarco:
So helpful. Please come back and check out the full podcast episodes where we dive into some of these elements in a little bit more detail.

In part one of this two-part series, Drs. Justin Abbatemarco, Valérie Biousse, and Nancy J. Newman discuss common myths around non-arteritic ischemic optic neuropathy (NAION).
Show transcript: 
Dr. Justin Abbatemarco:
Hello and welcome. This is Justin Abbatemarco, and I just got done interviewing Valérie Biousse and Nancy Newman on all things around non-arteritic anterior ischemic optic neuropathy. I think one of my favorite takeaways from our interview were breaking some common myths around this disorder. Valérie and Nancy, could you maybe talk about one or two that you think are important that people should know are not true about this disease?
Dr. Nancy J. Newman:
So thing number one is that it's just another stroke of the eye. We know that it likely does have some vascular background to it, but the reality is it's not a stroke like neurologists know a stroke. You don't need to do an embolic workup. It has to do likely with the anatomy that a person is born with or that they acquire that crowds the front of their optic nerve. Secondly, thing number two, that it's a disease only of old people. I think that we know that you can be as young as age 11 and have this happen, mostly because you have a small, crowded optic nerve head. Thing number three, steroids really have not been proven to be helpful in this disorder and should likely not be used unless you are trying to decrease the optic nerve head edema, and the patient is insisting that they have some treatment.
Dr. Justin Abbatemarco:
So helpful. Please come back and check out the full podcast episodes where we dive into some of these elements in a little bit more detail.

Dr. Margarita Fedorova outlines how genetic, environmental, and pathological factors interact in Parkinson's disease and what this means for patient counseling. 
Show citation: 
Blauwendraat C, Morris HR, Van Keuren-Jensen K, Noyce AJ, Singleton AB. The temporal order of genetic, environmental, and pathological risk factors in Parkinson's disease: paving the way to prevention. Lancet Neurol. 2025;24(11):969-975. doi:10.1016/S1474-4422(25)00271-6 
Show transcript: 
Dr. Margarita Federova:
Welcome to Neurology Minute. My name is Margarita Fedorova, and I'm a neurology resident at the Cleveland Clinic. Today we're exploring a framework for understanding how genetic, environmental, and pathological factors interact in Parkinson's disease and what this means for how we counsel our patients.
A personal view paper by Blauwendraat and colleagues, published in The Lancet Neurology in September 2025, addresses a critical question. We've identified over 100 genetic loci for Parkinson's, but how do they act?
The common saying is genetics loads the gun and environment pulls the trigger, but this paper suggests the relationship may be more complex. The key tool here is alpha-synuclein seeding amplification assays or SAAs.
These detect misfolded alpha-synuclein protein in cerebrospinal fluid. Over 90% of Parkinson's patients test positive for misfolded alpha-synuclein using this assay. But here's what's notable. 2% to 16% of neurologically healthy older adults also test positive with prevalence increasing with age.
This means there are more asymptomatic people with detectable alpha-synuclein pathology than people with actual Parkinson's disease. Most of these asymptomatic individuals will never develop symptoms. This raises an important question. What determines who converts to a disease and who doesn't?
By integrating SAA results with genetic data, researchers can examine whether genetic factors drive initial protein misfolding or whether they modulate the response to pathology triggered by environmental or random events.
Preliminary data suggests polygenic risk scores don't strongly associate with SAA positivity in healthy older adults. In other words, people with high genetic risk for Parkinson's aren't necessarily more likely to have misfolded alpha-synuclein if they're healthy.
This suggests most Parkinson's genetic risk factors may not be causing initial misfolding. Instead, they may be determining what happens afterward, such as whether the pathology progresses to clinical disease.
LRRK2 mutations support this model. About 33% of LRRK2 related Parkinson's patients are SAA-negative compared to only 7% in sporadic disease. This means many people with LRRK2 mutations develop Parkinson's without the typical alpha-synuclein pathology.
LRRK2 mutations also show varied pathology. Sometimes alpha-synuclein, sometimes tau, sometimes neither. This suggests LRRK2 may modulate responses to different initiating events rather than directly causing protein misfolding.
What does this mean for us as clinicians? Asymptomatic SAA-positive individuals could represent a window for intervention. If we can understand what protects them from converting to disease or what triggers that conversion, we could enable earlier identification of at risk individuals and potentially intervene before symptoms develop.
The authors call for large scale studies using SAAs in older populations, combined with genetic analysis and longitudinal follow-up. By integrating pathological biomarkers with genetic and environmental data, we can better understand the temporal sequence of events in development of Parkinson's.
This approach could fundamentally change how we think about disease prevention and early intervention, potentially allowing us to identify at risk individuals before symptoms appear and develop targeted prevention strategies.
That's your neurology minute for today. Keep exploring, and we'll see you next time.
If you want to read more, please find the paper by Cornelis Blauwendraat et al titled The Temporal Order of Genetic, Environmental and Pathological Risk Factors in Parkinson's Disease: Paving the Way to Prevention, published online in September 2025 in Lancet Neurology.