A Discussion Of How Environmental Factors Such As Pesticides May Affect Your Risk Of Parkinsons Disease
During my recent interview on Wisconsin Public Radio, many of the callers asked questions related to environmental risks of Parkinson’s disease , specifically, exposures related to farming. Those calls prompted me to delve further into this complicated and murky topic.
Before we start discussing specific factors in the environment that may increase risk of PD, let’s understand some basic ground rules that will help put this topic in perspective
With that background, let us begin.
Human Ipsc Studies Of Pd Highlight Converging Molecular And Cellular Pathways Across Genetic Subgroups
Our analysis of 385 iPSC-derived cell lines from 67 published studies reveals that many PD neuronal phenotypes are shared between genetically heterogeneous familial and sporadic patients . Notably, impairments in mechanisms involved in cellular waste recycling, mitochondrial function, neuronal morphology and physiology, and sensitivity to reactive oxygen species are most common across patient lines with varying genetic predispositions . The studies measured cellular phenotypes that occurred either spontaneously or in response to chemicals mimicking cellular aging and stress . It is important to note that the frequency of reported phenotypes in our meta-analysis may be biased because only few studies reported negative results 31,32,36,37,40,45,48,52,59,64,74,76,86. In addition, most cell lines were not systematically phenotyped without prior hypothesis and thus, there is likely to be an ascertain bias in these phenotypes. Less hypothesis-driven multimodal or omics analysis will help to address such bias41,72,76,77,78,79,80,87,90. Phenotypes caused by genomic predispositions allude to crosstalk and impairments in multiple pathways that act collectively to mediate selective degeneration of dopaminergic neurons in the substantia nigra and will be discussed in detail below.
Fig. 4: Phenotypic insights from iPSC studies of Parkinson’s disease.
Other Recent Studies Have Shown Certain Vitamins Can Decrease Your Risk Of Developing Parkinson’s
Other recent research shows that diet can affect your Parkinson’s risk, but in some cases, it’s for the better. A study published in January in the journal Neurology tracked the health of 41,058 men and women aged 18 to 94 for an average of 17.6 years. None of the participants were previously diagnosed with Parkinson’s disease. The study subjects were divided into three vitamin consumption groups, separating them by highest intake, moderate intake, and lowest intake.
The resulting data led the researchers to conclude that vitamin C and vitamin E can reduce your risk of Parkinson’s disease, with members of the highest consumption cohort of both vitamins being 32 percent less likely to develop the condition. “Our large study found that vitamin C and vitamin E were each linked to a lower risk of Parkinson’s disease, and we found the association may be even stronger when intake of both vitamin C and E is high,” study co-author Essi Hantikainen, PhD, said in a statement.
The Interplay Between Genomic Predispositions And Environmental Factors Leads To Parkinsons
In the mid-1990s, the connection between PD and underlying genetic mutations was established4,5,150. It is now evident that varying degrees of the interplay between genomic predispositions and aging and cellular stressors impose a risk for disease151 . Previous studies have shown vascular insults to the brain, repeated head trauma, neuroleptic drugs, exposure to pesticides, and manganese toxicity increase the risks of developing symptoms of PD152,153,154. In addition, advancing age can also cause a cascade of stressors within the substantia nigra, which weakens the neurons and their ability to respond to further insults155,156. Ultimately, the uniqueness of the interactions between genes and the environment makes the development of a single treatment for PD difficult as they give rise to a spectrum of neuronal phenotypes that can be unique to individual patients . The development of a model with the ability to replicate the genomic and epigenetic aspects of the disease is crucial . As increasing evidence suggests that genetic mutations are key modulators of disease initiation and progression, the identification and understanding of the various genomic predispositions are required for the development of better-targeted treatments to slow the disease progression.
Fig. 1: A combinatorial spectrum of genetic risks, cellular stressors, and brain cell dysfunctions causes Parkinson’s disease.Full size image
How Is Constipation An Early Warning Sign Of Parkinson’s It’s Such A Common Problem
A: It’s not as specific as other prodromal symptoms, like anosmia. The rate at which people with chronic and unexplained problems with constipation develop Parkinson’s disease is not as easy to pin down. But if someone has unexplained, persistent constipation, it should at least be noted, as it could be considered prodromal.
People Who Already Have Pd: Should I Get Tested And What Do I Do With The Results
Up until recently, even people with PD with a very extensive family history of PD would not necessarily receive genetic testing because there were no clear uses for the results. There has been research directed at figuring out whether PD caused by or associated with certain mutations have particular clinical characteristics . However, there remains so much variability in clinical characteristics even among people with the same PD mutation, that there are still no clear practical implications in knowing whether a PD patient harbors a particular mutation. There is also, so far, no difference in treatment or management of PD whether or not the patient harbors one of the known mutations. That may change however, with the advent of clinical trials that target particular mutations.
There are two genes that have received particular attention recently because medications are being developed that target those with mutations of these genes.
GBAis a gene that increases the risk of developing PD. The gene encodes for the GBA enzyme, a protein used by the body to break down cellular products. Having two abnormal GBA genes causes Gaucher’s disease, which is characterized by the buildup of these cellular products resulting in fatigue, bone pain, easy bleeding and an enlarged spleen and liver. When a person inherits only one abnormal gene, he or she does not develop Gaucher’s disease, but does incur a small increased risk of PD. Most people with one mutated GBA gene do not develop PD.
Drinking Well Water Is Linked With A Higher Likelihood Of Developing Parkinson’s
A growing body of research suggests that there is a correlation between drinking well water and developing Parkinson’s Disease later in life. One particular study, conducted by a team at UCLA and published in the journal Environmental Health Perspectives, found that those who consume well water are statistically more likely to develop PD. After reviewing the medical records and personal histories of 700 people living in California’s farm belt between 1974 and 1999, they determined that those who ultimately developed PD had consumed private well water on average 4.3 years longer than those who did not.
Besides Medication What Other Approaches Should I Use To Deal With This Disease
Medication can certainly reduce the complications of Parkinson’s disease, but it’s not the only way to deal with it. There are other approaches that you may need to consider in order to feel and live much better with this progressive disease. Here are some of them:
- Educate yourself about the disease
Exercise Helps Prevent Fight Parkinson’s Disease From The Harvard Health Letter
Parkinson’s is a brain disease that affects the body and how it moves. Early symptoms include tremors, a shuffling gait, and an overall slowing of physical movement. Yet exercise may be one of the best — and most underutilized — ways of combating the condition, according to the March 2012 Harvard Health Letter.
Several prospective studies that followed tens of thousands of people for many years have shown a correlation between exercise earlier in life and a reduced chance of developing Parkinson’s later on. Exercising in your 30s and 40s — decades before Parkinson’s typically occurs — may reduce the risk of getting Parkinson’s disease by about 30%, notes the Health Letter. Some experts believe the exercise must be vigorous to make a difference. However, because this kind of research can’t prove cause and effect, there is the possibility of “reverse causation”: that is, exercise may not prevent Parkinson’s disease, but instead a very early “preclinical” form of the disease, without clear symptoms, may make people less willing or able to exercise in the first place.
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What Are The Chances Of Getting Parkinsons Disease Sarcastically Speaking
Someone asked me, what are the chances of getting Parkinson’s disease? So, I did some research and came up with the following.
Lighter colored hair. Yes, that’s right. A person with black hair has the best chance of escaping a diagnosis of PD than that of a person with red or blonde hair, red being the greatest chance. I don’t think dyed hair counts.
Family history.Hereditary factors/genetics can play a part. If you have a close relative who has Parkinson’s disease your chances increase.
Men tend to be more at risk than womenfor unknown reasons. However, this fact can also depend on what country you live in.
If you are over the age of sixty, the likelihood of developing PD is greater. However, there is a very rare known case of PD starting at the age of two.
The Amish communityseems to have the highest rate of PD among any other communities. It is thought that the culprit may be all the pesticides used in their farming. Which leads to… Exposure to toxins playing a large part in some PD cases as well as those individuals who relied on well water for drinking and cooking. This is due to the chemicals/pesticides found in the water. It is said that Nebraska has the highest rate of PD in the United States, most likely due to the pesticides used in their farming, as well.
Trauma to the head may play a role as damage is done to the dopamine producing neurons in the brain. If you were one to bang your head against the wall in frustration, well… you shouldn’t have.
Depression And Anxiety Are Also Early Warning Signs Of Parkinson’s How So
A: Like the other symptoms discussed here, late-onset depression and anxiety are nonmotor prodromal manifestations of the condition. It’s not that everyone who is depressed will get Parkinson’s, and the numbers are lower than they are for symptoms like anosmia and REM behavior disorder. But the link is important to explore, and we are doing more research on it all the time.
Genetic Predispositions Reducing Differentiation Yield Of Mda Neurons
In vitro neural development was impaired in neural lines derived from patients carrying LRRK2, PRKN, SNCA, and sporadic mutations43,49,74,93. In four independent studies, the differentiation potential of neural progenitor cells derived from patients was significantly reduced, demonstrated by low yields of neurons in comparison with control lines43,49,74,81,94. A recent review presented the idea that PD is attributed to significant neurodevelopmental defects, which may increase the susceptibility for disease onset224. If confirmed, identifying genetic predispositions that contribute to early developmental defects in iPSC-PD may assist the development of novel PD therapies. However, these phenotypes may appear in conflict with other studies53,55,76 capable of generating functional neurons from cell lines with similar mutations. The differences could be due to varying protocols, which may be more or less stressful for the cells.
What Is Rem Behavior Disorder And How Is It Connected To Parkinson’s
A: REM behavior disorder is different than other sleep problems, like insomnia. People who have it may jerk or kick — it’s as though they are acting out their dreams. In a similar pattern to anosmia, people with idiopathic REM sleep behavior disorder have at least a 50 percent chance of eventually developing Parkinson’s disease.
Will Findings From Pd Ipsc Models Translate To Human Clinical Trials
Given the apprehensions that in vitro studies may be too artificial, human iPSC-derived neural progenitors may be transplanted into animal brains244,245,246,247. Besides ethical barriers, xenografts also raise the possibility that the healthy host tissue compensate for the impairment of the transplanted cells. Yet, if the phenotypes observed in vitro are recapitulated in vivo, pharmacological treatments could be assessed in a systemic environment, with much more realistic dosage and administration methods.
Studies On Gaucher Disease Parkinson Disease And Lewy Body Dementia
Gaucher disease, Parkinson disease and Lewy body dementia all involve abnormal proteins. Proteins are chemicals that the body uses for many essential functions, and when they do not work properly it can cause problems that range from nondetectable to severe.
Recent findings on the relationship between Gaucher disease, Parkinson disease and LBD include:
- Researchers have found that many of the same genes and proteins are involved in these diseases. Scientists are investigating how this overlap relates to the disease process.
- Patients with Parkinson disease or LBD with mutations in the GCase gene typically have an earlier disease onset and more severe symptoms.
- Imaging studies and tests can help identify early onset Parkinson disease in patients with low GCase enzyme activity. This is why it is so important that patients with Gaucher disease see a specialist regularly who can monitor their health. Learn more about optimizing your health with Gaucher disease.
What Are The Chances Of Getting Parkinsons If My Siblings Have It
Three older siblings have Parkinson’s disease, but the three younger siblings have shown no symptoms yet. Genetic testing for Parkinson’s can give answers.
Dr. Zbigniew K. Wszolek responds:
The chance that you have the genetic form of Parkinson’s disease is relatively high, but it’s impossible to say how high without knowing more about your family history. For example, knowing if you have a parent or grandparent with Parkinson’s can clarify whether your family carries one of five major genes thought to cause the disease.
The best advice I can give you would be to visit a genetic clinic—available at most major universities—where you can undergo a test to learn whether you are a genetic carrier or not. A genetic counselor can also explain to you the pros and cons of testing. It’s important to realize that knowing you are a mutation carrier will not change anything, because we don’t have a treatment available to halt progression of the disease. But some people are interested in genetic testing because they feel they can use the information to modify their lifestyle; some may choose not have children, for example, while others may decide to join clinical trials. Also, knowing whether or not you are a gene carrier may bring some peace of mind.
How Environmental Factors And Aging Can Be Recapitulated In Vitro
An obvious limitation of in vitro models is the lack of environmental context. The influence of nongenetic factors is not recapitulated in the basal phenotype of patient-derived neurons. For example, the influence of head trauma of a boxer with sporadic PD will not be recapitulated by default in reprogrammed neurons. An alternative would be to transplant the patient-derived neurons in animals and simulate the trauma on the animal. Similarly, influence of decades of aging of the human brain is difficult to reproduce in vitro in a few months within the boundaries of feasible experimental design. Brains in a dish will always be an imperfect experimental model. However, many tricks can be used to recapitulate the environmental and aging stress in vitro. Table 2 summarizes a list of reagents that have already been used in iPSC neuronal culture to mimic oxidative stress, proteostatic stress, mitochondrial stress, synaptic stress, ER stress, inflammation, and cellular aging. An interesting example is progerin, a truncated form of lamin A associated with premature aging. Increasing the expression of progerin in iPSC neurons can recapitulate at least some aspect of cellular aging in vitro71. Human iPSC-derived dopamine neurons overexpressing progerin displayed specific phenotypes such as neuromelanin accumulation. In addition, PD patient-derived neurons revealed disease-related phenotypes that required both genetic susceptibility and induced-aging in vitro71.
Projected Estimates Of Parkinsons Disease With Aging Population
As the life expectancy has increased worldwide, it is expected that the burden of chronic diseases, like PD, will continue to grow. It is estimated that the number of people with PD in 2005 totaled between 4.1 million and 4.6 million and that number will more than double by 2030 to between 8.7 million and 9.3 million.7
Neuroinflammation Exacerbates Neurodegeneration In Sporadic Pd
Midbrain neurons derived from sporadic patients showed increased susceptibility to the effects of adaptive immune cells72. Sporadic patient neuronal lines co-cultured with T-lymphocytes exhibited substantial signs of cell death mediated by IL-17–IL-17R signaling and activation of NFkB72. Similarly, IL-17 treatment resulted in increased neuronal death72. Inflammation in the central nervous system and periphery are key hallmarks of PD220. Increasing evidence implicates the role of microglia in neuronal loss, though the underlying mechanisms remain to be determined221,222. RNA-seq analysis of astrocytes derived from LRRK2-G2019S iPSCs highlighted dysregulation in genes involved in the extracellular matrix, which may reduce the neuroprotective capacity of astrocytes in PD78. Investigating the role of neuroinflammation in patient-derived microglia may also contribute to the understanding of the selective vulnerability of mDA neurons in sporadic and late-onset PD223.
Do People Actually Lose Their Sense Of Smell With Parkinson’s
A: Yes. It’s a condition called anosmia, and if you have it with no other disease , you have at least a 50 percent chance of developing Parkinson’s disease in the next five to 10 years. What happens is that alpha-synuclein, the protein that clumps in the part of the brain that regulates dopamine and leads to Parkinson’s disease, also aggregates in the olfactory bulb, the part of the brain responsible for your sense of smell. This happens well before the protein accumulations cause motor symptoms.
What Lifestyle Changes Can I Make To Ease Parkinsons Symptoms
Exercise: Exercise helps improve muscle strength, balance, coordination, flexibility, and tremor. It is also strongly believed to improve memory, thinking and reduce the risk of falls and decrease anxiety and depression. One study in persons with Parkinson’s disease showed that 2.5 hours of exercise per week resulted in improved ability to move and a slower decline in quality of life compared to those who didn’t exercise or didn’t start until later in the course of their disease. Some exercises to consider include strengthening or resistance training, stretching exercises or aerobics . All types of exercise are helpful.
Eat a healthy, balanced diet: This is not only good for your general health but can ease some of the non-movement related symptoms of Parkinson’s, such as constipation. Eating foods high in fiber in particular can relieve constipation. The Mediterranean diet is one example of a healthy diet.
Preventing falls and maintaining balance: Falls are a frequent complication of Parkinson’s. While you can do many things to reduce your risk of falling, the two most important are: 1) to work with your doctor to ensure that your treatments — whether medicines or deep brain stimulation — are optimal; and 2) to consult with a physical therapist who can assess your walking and balance. The physical therapist is the expert when it comes to recommending assistive devices or exercise to improve safety and preventing falls.
The Importance Of Establishing Parkinsons Prevalence Numbers
Parkinson’s Prevalence estimates will help the Parkinson’s Foundation attract the attention of federal and state government as well as the pharmaceutical industry to the growing need and urgency in addressing PD. This is an important first step to better understanding who develops PD and why.
The next phase of this study will be to determine the rate of PD diagnosis or incidence, how that has changed over time and what is the rate of mortality among those affected by PD. Determining the prevalence and incidence will allow the PD community to effectively advocate for additional money and resources necessary to support Parkinson’s research.
Parkinson’s Foundation Prevalence Project numbers highlight the growing importance of optimizing expert Parkinson’s care and treatment for people with Parkinson’s, which would help future caregivers and ease the strain on health and elder care systems.
Scientifically Backed Ways To Prevent Parkinsons Disease
Dopamine plays a major role in a variety of mental and physical functions, including:
- Voluntary movement
- General behavior
Parkinson’s now afflicts roughly 1.5 million people in the United States alone, with primary symptoms being body tremors, slow movement, rigid limbs, reduced memory, a shuffling gait and speech impairment. So we have to ask:
1.) What causes it?
2.) How do we prevent it?
Currently there isn’t a known cure, and it’s not fully understood what causes the dip in dopamine; however, we know that aging is the single most important risk factor for PD, with inflammation and stress contributing to cell damage. And we now know enough about the disease to understand the preventative measures that counter the aging and death of the neurons under attack.
Because there is no known cure, it’s critical that we prevent the disease before symptoms arise. Granted, thanks to recent advancements in modern surgical procedures, there are some safe surgeries that can mitigate some of the more severe symptoms associated with PD. The most common one now is deep brain stimulation, in which they implant an electrode into the brain that can stop some of the more severe symptoms of Parkinson’s.
But this article will try to keep it from getting to that point. The less drugs and surgery we can have in our lives, the better.
Learning From Genetic Analyses Of Pd Casecontrol Studies
We analyzed the reports from 12 international studies94,157,158,159,160,161,162,163,164,165,166,167, totaling 5650 persons living with PD in North America, Europe, and Australia. We confirmed that globally only 15% of patients report a family history of PD symptoms, while the remaining 85% of the PD population are classified as sporadic PD . However, the distinction between genetic predispositions in familial and sporadic PD is blurry. No single-gene mutation in PD has a 100% penetrance. Instead, most likely, multiple genetic risk factors act in synergy to increase the chances of both familial and sporadic PD. Such genetic susceptibilities interplay with aging and environmental factors in both familial and sporadic PD.
Fig. 2: The genomics of Parkinson’s disease: prevalence and penetrance.
a In the world-wide population of people living with PD, ~85% of PD cases are sporadic and the remaining are familial . b Genetic mutations occur at low and varying frequencies in the PD world population . Data represented as the mean±SEM. c GWAS data suggests risk variants in fPD genes tend to be less prevalent in PD cases . d Single nucleotide polymorphisms in over 44 genomic regions show significant association to PD. Each point presents an independent SNP hit associated with PD.
Parkinsons Is A Progressive Disease Whats Meant By That
Parkinson’s is not like a flu or fever that you take antibiotics and recover in 2-3 days. It is a progressive disease; that means it develops and becomes worse over time.
At first, some abnormal changes appear in the brain that begins to damage parts of the brain responsible for movements. These changes are gradual and the effect is limited to the brain only.
After 15-20 years, the damage reaches the level where it begins to affect body normal movements. This is the early stage where typical symptoms of the disease start to develop. These early symptoms are mild and appear either on one or both sides of the body. At this stage, the disease can easily be diagnosed clinically.
After 10 years of diagnosis, the brain’s ability of performing movement functions is severely affected. The symptoms become severe and begins to affect the patient’s daily life activities. This is called the mid-stage of the disease.
When the disease has passed 20 years, it reaches its advanced stage. At this stage, the symptoms become very severe and most often the patient needs assistance for mobility.
What Are The Surgical Treatments For Parkinsons Disease
Most patients with Parkinson’s disease can maintain a good quality of life with medications. However, as the disease worsens, medications may no longer be effective in some patients. In these patients, the effectiveness of medications becomes unpredictable – reducing symptoms during “on” periods and no longer controlling symptoms during “off” periods, which usually occur when the medication is wearing off and just before the next dose is to be taken. Sometimes these variations can be managed with changes in medications. However, sometimes they can’t. Based on the type and severity of your symptoms, the failure of adjustments in your medications, the decline in your quality of life and your overall health, your doctor may discuss some of the available surgical options.
What Is The Outlook For Persons With Parkinsons Disease
Although there is no cure or absolute evidence of ways to prevent Parkinson’s disease, scientists are working hard to learn more about the disease and find innovative ways to better manage it, prevent it from progressing and ultimately curing it.
Currently, you and your healthcare team’s efforts are focused on medical management of your symptoms along with general health and lifestyle improvement recommendations . By identifying individual symptoms and adjusting the course of action based on changes in symptoms, most people with Parkinson’s disease can live fulfilling lives.
The future is hopeful. Some of the research underway includes:
- Using stem cells to produce new neurons, which would produce dopamine.
- Producing a dopamine-producing enzyme that is delivered to a gene in the brain that controls movement.
- Using a naturally occurring human protein – glial cell-line derived neurotrophic factor, GDNF – to protect dopamine-releasing nerve cells.
Many other investigations are underway too. Much has been learned, much progress has been made and additional discoveries are likely to come.
Certain Chemicals Lead To More Dangerous Contamination
Those who consumed well water in close proximity to certain pesticides were found to be at a higher risk than others. In particular, the UCLA study found that people drinking well water within 500 meters of fields sprayed with pesticides had a 66 percent increased risk of later developing PD. Those drinking well water near land treated with the insecticides propargite or chlorpyrifos had a 90 percent higher risk. This translates into a nearly doubled risk of someday developing Parkinson’s.
“The chemical with the most data linking it to an increased PD risk is paraquat,” says the APDA, referring to a chemical herbicide used to kill weeds. Exposure to paraquat is “associated with a 2-3 fold increased PD risk over the general population,” the organization warns.
If you regularly consume well water, especially in areas being sprayed with chemical pesticides or herbicides, be sure to have your water filtered and regularly tested.
Why Genetic Testing For Parkinsons Disease Is Complex:
- There are many genes that are associated with the development of PD. This list continues to grow as more genes are discovered. Testing of only some of these genes is available in commercial labs.
- The majority of people with PD, even those with a family history of PD, do not harbor one of these identified abnormal genes. The genetic contribution to PD in these people is yet to be discovered.
- For a particular gene there may be a number of different mutations associated with disease, some of which are more common than others. Commercial testing may identify only the most common of the mutations, and therefore not capture everyone who carries a disease-causing mutation.
- Conversely, only particular mutations in a gene may be associated with disease. Commercial testing may identify changes in a gene that may not have clinical consequences. This can be confusing for patients who even after genetic testing may not know whether they harbor a disease-causing mutation.
- Different mutations can be enriched in different ethnic populations. For example, Ashkenazi Jews and North African Berbers have an increased risk of carrying Leucine rich repeat kinase 2 mutations. Glucocerebrosidase mutation frequency also varies greatly with ethnicity and is also increased among Ashkenazi Jews.
In addition to the above, it is important to realize that not all genes associated with PD contribute to disease in the same way:
What Medications Are Used To Treat Parkinsons Disease
Medications are the main treatment method for patients with Parkinson’s disease. Your doctor will work closely with you to develop a treatment plan best suited for you based on the severity of your disease at the time of diagnosis, side effects of the drug class and success or failure of symptom control of the medications you try.
Medications combat Parkinson’s disease by:
- Helping nerve cells in the brain make dopamine.
- Mimicking the effects of dopamine in the brain.
- Blocking an enzyme that breaks down dopamine in the brain.
- Reducing some specific symptoms of Parkinson’s disease.
Levodopa: Levodopa is a main treatment for the slowness of movement, tremor, and stiffness symptoms of Parkinson’s disease. Nerve cells use levodopa to make dopamine, which replenishes the low amount found in the brain of persons with Parkinson’s disease. Levodopa is usually taken with carbidopa to allow more levodopa to reach the brain and to prevent or reduce the nausea and vomiting, low blood pressure and other side effects of levodopa. Sinemet® is available in an immediate release formula and a long-acting, controlled release formula. Rytary® is a newer version of levodopa/carbidopa that is a longer-acting capsule. The newest addition is Inbrija®, which is inhaled levodopa. It is used by people already taking regular carbidopa/levodopa for when they have off episodes .