What Environmental Factors Cause Parkinson’s

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Parkinson’s Disease Risk Factors

Although a primary cause for Parkinson’s disease is yet to be identified, a number of risk factors are clearly evident.

Advancing age– Although there is the occasional case of the disease being developed as a young adult, it generally manifests itself in the middle to late years of life. The risk continues to increase the older one gets. Some researchers assume that people with Parkinson’s have neural damage from genetic or environmental factors that get worse as they age.

Sex- Males are more likely to get Parkinson’s than females. Possible reasons for this may be that males have greater exposure to other risk factors such as toxin exposure or head trauma. It has been theorised that oestrogen may have neuro-protective effects. Or, in the case of genetic predisposition, a gene predisposing someone to Parkinson’s may be linked to the X chromosome.

Family history– Having one or more close relatives with the disease increases the likelihood that you will get it, but to a minimal degree. This lends support to the idea that there is a genetic link in developing Parkinson’s.

– Post menopausal who do not use hormone replacement therapy are at greater risk, as are those who have had hysterectomies.

Low levels of B vitamin folate– Researchers discovered that mice with a deficiency of this vitamin developed severe Parkinson’s symptoms, while those with normal levels did not.

The Search For Environmental Causes Of Parkinson’s Disease Moves Forward

Date:

IOS Press

Summary:

Scientists evaluate promising research hypotheses for understanding environmental triggers in Parkinson’s disease and propose future directions for research.

Environmental factors are widely believed to play a key role in the development of Parkinson’s disease , but little is known about specific environmental triggers. Writing in the Journal of Parkinson’s Disease, scientists review novel research hypotheses and approaches that may help better define the role of environment in the development of PD, especially before a diagnosis can be made based on the characteristic motor dysfunction for which PD is known.

Late-onset sporadic PD takes decades to develop, and by the time of diagnosis, some of the neurodegenerative changes are too advanced to slow down, stop, or reverse. On the other hand, environmental factors that cause or trigger its development and modify its progression may come into play during the “prodromal phase,” decades before specific signs and symptoms develop. “This prodromal stage is of major interest for prevention efforts,” explained the authors. “Targeting factors that enter the body via the nose or gut has become even more important since the discovery that the alpha-synuclein protein-related Lewy pathology, which is characteristic of PD, was identified in the nervous systems of the olfactory pathway and the digestive tract.”

Braak Hypothesis

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How Does Environment Come Into It

Your environment is a hard one to pin down. Partly, that’s because it covers a lot of ground. It’s everything that’s not your genes, which could mean where you live, what you eat, chemicals you’ve come into contact with, and more.

Not only that, but it could take years for the effects from something in your environment to show up. So far, doctors have a lot of clues but no smoking gun. So you could have people who live or work in an area around chemicals tied to Parkinson’s, but many of them don’t get it.

Some research shows links between Parkinson’s and:

• Agent Orange, a chemical used to destroy trees and crops in the Vietnam War.
• Certain chemicals used in farming, such as insecticides, herbicides, and fungicides.
• Some metals and chemicals used in factories, such as manganese, lead, and trichlorethylene .

These can come into play based on where you live, what you do for work, or if you served in the military. Sometimes, these chemicals seep into well water, so that’s one more way they can affect you.

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Parkinsons Driven By Inflammation Genetics And The Environment

David Standaert, M.D., Ph.D., said that early interventions involving anti-inflammatory drugs could help to slow progression of the disease.

In 1817, James Parkinson published An Essay on the Shaking Palsy, describing the disease that now bears his surname. The British surgeons proposed treatment bloodletting proved ineffective, and the intervening two centuries led to no breakthroughs for patients.

The reality is that today, we still dont have a treatment that slows or alters the progression of Parkinsons disease, said David Standaert, M.D., Ph.D., during a Jan. 8 talk at NIEHS. He is chair of the neurology department at the University of Alabama at Birmingham . We can help patients function better, but were not changing the underlying nature of the disease.

Parkinsons disease is complex, involving genetic and environmental factors, and their interaction. Guohong Cui, M.D., Ph.D., head of the NIEHS In Vivo Neurobiology Group, invited Standaert to discuss the role immunity plays in the disorder. Both researchers seek to discover ways to slow advancement of the condition and make it less severe.

Dr. Standaert is an established researcher in the Parkinsons field, which is one of the major areas my lab works in, said Cui. His team examines how pesticides interact with genetic factors associated with the disease and ways to slow dopamine loss, which is a hallmark of the disorder.

Pesticide And Herbicide Exposure

A strong link has been shown between PD and exposure to pesticides and herbicides. We need more Parkinsons-specific research to better understand what causes PD and to work to prevent it and help eliminate the risk of getting the disease, when it comes to all environmental risk factors and whether genetics can cause an increased risk in developing Parkinsons.

One herbicide that has been linked to Parkinsons is paraquat, a widely used commercial herbicide in the U.S. that is banned in 32 countries, including the European Union and China. The Parkinsons Foundation, along with the Unified Parkinsons Advocacy Council, signed two letters to the U.S. Environmental Protection Agency encouraging them to cancel the registration of paraquat based on strong scientific research linking the herbicide to Parkinsons disease. In October 2020, the EPA re-approved paraquat for use in the U.S. Without additional action, paraquat will remain legal for sale and use in the U.S. for the next 15 years.

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What To Do If You Think You May Have Parkinson’s Disease

• Trembling of hands, arms, legs, jaw and face

• Stiffness of the arms, legs and trunk

• Slowness of movement

• Poor balance and coordination

The Parkinson’s Foundation offers people with PD genetic testing and counseling at no cost through its ongoing research study, PD GENEration: Mapping the Future of Parkinson’s Disease, says Beck. The Parkinson’s Foundation also has resources available at Parkinson.org, or you can call the Parkinson Foundation Helpline at 1-800-4PD-INFO . And to get through this pandemic at your healthiest, don’t miss these 35 Places You’re Most Likely to Catch COVID.

Causes And Risk Factors Of Parkinsons Disease

Genetics aside, environmental risk factors include head injury, area of residence, occupation, solvents and polychlorinated biphenyls, as well as exposure to pesticides, herbicides, and metals. Head injury refers to a traumatic brain injury that alters the level of consciousness, which seems to increase the risk of developing Parkinsons disease some years later. As for area of residence and occupation, there are differences in both the geographic distribution of Parkinsons disease and the incidence of Parkinsons disease in certain occupational categories. Pesticide and herbicide exposure are linked to Parkinsons disease, while metal exposure seems to be related to its development, but the exact connection is not entirely understood. Lastly, high concentrations of PCBs have been found in the brains of people with Parkinsons disease.

Apart from potential genetic causes and environmental risk factors, other risk factors include age and gender. More specifically, the number of people diagnosed with Parkinsons disease increases with age, regardless of sex, and approximately 1 percent of people over the age of 60 have the disease. As for gender, men are more likely to have Parkinsons disease than women. In rare cases, Parkinsonian symptoms can be caused by MPTP. This is a toxic impurity that can be found in the recreational drug MPPP, or desmethylprodine, which is a synthetic opioid.

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How You Lose Dopamine Production

Damaged nerve cells can be what results in a decreased ability of the brain to create dopamine. Generally, some kind of degradation of the brain cells will reduce dopamine production.

There is some genetic link to parkinsons disease. For example, specific genetic mutations can impact the dopamine production. Far more common is that exposure to something in the environment can impact the brain.

Environmental Factors: Etiological And Disease

From 1817 when Dr. James Parkinson first described 6 patients with the condition that would later bear his name , much progress was made in the following 150years. It became known that the SN was the site affected by PD pathology together with the presence of cytoplasmic inclusions, and levodopa became available as the first effective symptomatic drug treatment of PD in 1960s . However, the etiology of PD remained elusive.

Table 1 Examples of environmental factors and their biologic correlates

The most robust beneficial environmental factor associated with PD is cigarette smoking which has been seen in early case-control studies and then confirmed in more recent large prospective cohorts. Active smokers have 50% lower risk of PD compared to never smokers . There is a strong dose-response relationship including duration, intensity, pack-years and years since last smoking: PD risk decreases with increasing duration of smoking and increases again with time since quitting . Preliminary reports also support an inverse relationship between passive smoking, smokeless tobacco use and PD .

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Need For Laws That Can Help Prevent Parkinsons

The;Parkinsons Foundation;estimates that nearly a million Americans alone have been diagnosed with the condition. Parkinsons genetic causes may factor into it but that is not the truth for the large majority of cases. And unfortunately, the numbers are anticipated to climb exponentially over the next decade.

The solution that could prevent the need for Parkinsons therapy or Parkinsons medication is to simply bolster demands for the government to address the health risk.

There are sufficient studies and statistics to back the fact that air pollutants play a big part in the diseases progression. Emphasizing the necessity for a focused public health strategy might just be a starting point to decrease the numbers and defy the expectations for the future.

Now Is A Major Opportunity To Move Forward

Although still somewhat controversial, the Braak hypothesis presents a unique hypothetical framework of PD development that may allow us to better conceptualize steps of PD prodromal development and environmental contributions. According to this hypothesis, PD Lewy pathology develops in six sequential stages, first in the olfactory bulb or enteric nerves , years if not decades, before spreading to the substantia nigra where dopaminergic neuron death occurs . In support of this hypothesis, recent clinical and epidemiological studies have clearly documented a wide range of nonmotor symptoms in PD patients, and some symptoms such as olfactory impairment , REM sleep behavior disorder , and constipation may have developed years, if not decades, prior to PD clinical diagnosis. While there are still substantial challenges to adequately define prodromal PD, by using these symptoms as noninvasive intermediate phenotypes, we may be able to bring new insights into this black-box of PD prodromal development by identifying factors that initiate PD pathogenesis, lead to these intermediate phenotypes, or modify progression to clinical PD . This framework may fundamentally improve understanding of PD prodromal development and contributions from environmental factors.

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De Miranda Tackles Organic Solvents

For decades, researchers have drawn links between environmental exposures and Parkinsons disease, said De Miranda in an Environmental Factor interview.

The most commonly researched exposures involved pesticides. That link has remained strong, but Parkinsons is not only in people who live around pesticides, she said.

There have been other, smaller links involving different compounds. For example, Im very interested in what are called organic solvents. These might be found in more urban areas as opposed to pesticides found more in rural areas.

Weve found in our experimental models that an LRRK2 mutation increases susceptibility to environmental exposures. Im addressing whether an individual with such a mutation who is exposed to even very low levels of an environmental contaminant will be more likely to develop Parkinsons disease.

If the answer is yes, are there ways we can intervene, perhaps by simply removing that chemical from their personal environment? For example, if they are living in an area that has a lot of water contamination of organic solvents, could we filter their water and try to protect them that way?

Im also interested in expanding my research to compounds that are structurally similar but have never been studied in the context of Parkinsons disease risk.

I think thats really important is there a huge swath of compounds that were missing that could potentially pose risk to people?

The Five Environmental Causes Of Parkinsons Disease

Parkinsons disease is a brain disorder that develops and becomes worse over time. The typical symptoms of the disease include tremor, stiffness, slowness of movement, and balance problems.; These symptoms develop when the brain lost its ability to produce a sufficient amount of dopamine, a neurotransmitter responsible for controlled body movement.

Researchers have identified a variety of environmental factors that are linked to Parkinsons disease. Some of these factors may directly cause the disease symptoms, others may increase the risk of developing it.

Here are the 5 main environmental factors that are linked to Parkinsons disease development.

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What Role Do Genes Play

Your genes are like your body’s instruction book. So if you get a change in one of them, it can make your body work in a slightly different way. Sometimes, that means you’re more likely to get a certain disease.

There are several genetic mutations that can raise your risk for Parkinson’s, each by a little bit. They have a part in about 1 in 10 cases.

If you have one or more of these changes, it doesn’t mean you’ll get Parkinson’s. Some people will, but many won’t, and doctors don’t know why. It may have to do with other genes or something in your environment.

How Environmental Factors Could Cause Parkinsons Disease

Scientists differ about the extent that brain cells are impacted by environmental factors. However, the statistics associated with the disease show that the environment can play a very large role in whether parkinsons disease develops.

Most often, it is exposure to toxic chemicals that could play a role in the development of Parkinsons disease. Usually, these combine with genetic factors to produce the conditions that cause Parkinsons.

Increasing scientific evidence suggests that Parkinsons may be caused by environmental factors such as exposure to herbicides such as Paraquat.

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Genetics: Insights Into Etiology

Improvement in genetic analysis techniques in the 1990s led to the discovery of the first genetic cause of PD: mutations in the SNCA gene encoding -synuclein . At around the same time, -synuclein was found to be the major constituent of LB, the pathological hallmark of PD . Subsequently, multiplications of the SNCA gene have been found to cause PD with penetrance increasing with gene dosage . These discoveries brought -synuclein to center stage in the study of the pathogenesis of PD and led to the hypothesis that during different stages of the disease, -synuclein spreads in a stereotypical way within the nervous system in a prion-like fashion .

Table 2 Examples of genes associated with PD risk

Other Relevant Environmental Exposures

Although not the focus of this article, the Braak hypothesis also provides strong rationales to systematically examine several other environmental exposures that have not been well studied in the context of PD development such as organic solvents , high temperature cooked meats and heterocyclic amines , respiratory or GI infections and inflammation , and the use of antibiotics and antiviral therapies .

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What Are The Major Challenges In Searching For Environmental Causes Of Pd

The fact that late-onset sporadic PD takes decades to develop and the lack of understanding of this prolonged prodromal phase present a major challenge to understand environmental contributions to PD. In this disease development paradigm, causative exposures that initiate PD pathological process may have to occur and be documented decades before disease clinical diagnosis, which is often infeasible in epidemiological studies. Further, once neurodegeneration is initiated, many environmental and genetic factors may come into play to modify PD progression during the decades of prodromal disease development. As a consequence, even the most robust epidemiological findings, including those from longitudinal cohorts, are subject to alternative explanations. For instance, smokers have a robust and substantially lower risk for PD than non-smokers in all types of epidemiologic studies . While a causal interpretation that cigarette smoking reduces PD risk is appealing, alternative hypotheses such as reverse causation and confounding by personality and other unknown risk factors are equally possible . Similar analogies can be easily extended to most, if not all, of the presumed protective modifiable risk factors afore-mentioned.

Mutations And Toxins Increase Risk

When mutated, the LRRK2 protein can worsen problems caused by alpha-synuclein. It is one of the most common genetic causes of Parkinsons. In our clinic, about 2 to 3;percent;of patients have LRRK2 mutations, he noted. Those mutations may cause Parkinsons by cranking up sensitivity of the immune system they may increase the magnitude of the response to alpha-synuclein.

But other factors bear consideration. To study the mechanisms responsible for Parkinsons disease, there is a need for model systems that replicate the effects of environmental toxins, said Standaert. He highlighted research by NIEHS grantee Briana De Miranda, Ph.D., of the University of Pittsburgh. She studies, among other things, how organic solvents may boost susceptibility to Parkinsons disease in individuals with LRRK2 mutations.

Standaert said the fact that inflammation may cause the disorder to advance more than it otherwise would means that anti-inflammatory drugs could hold promise. We have immunologic treatments for a lot of other diseases, such as inflammatory bowel disease, psoriasis, and multiple sclerosis, Standaert said in an interview. Could we use one of those or something similar in Parkinsons disease to slow its progression?

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