Wednesday, December 7, 2022
Wednesday, December 7, 2022
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Risk Factors For Parkinson Disease

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Parkinson’s Disease (Shaking Palsy) – Clinical Presentation and Pathophysiology

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How Do I Take Care Of Myself

If you have Parkinsons disease, the best thing you can do is follow the guidance of your healthcare provider on how to take care of yourself.

  • Take your medication as prescribed. Taking your medications can make a huge difference in the symptoms of Parkinsons disease. You should take your medications as prescribed and talk to your provider if you notice side effects or start to feel like your medications arent as effective.
  • See your provider as recommended. Your healthcare provider will set up a schedule for you to see them. These visits are especially important to help with managing your conditions and finding the right medications and dosages.
  • Dont ignore or avoid symptoms. Parkinsons disease can cause a wide range of symptoms, many of which are treatable by treating the condition or the symptoms themselves. Treatment can make a major difference in keeping symptoms from having worse effects.

Lewy Bodies And Alpha

In addition to the dopamine deficiency and neuronal loss, PD is also associated with a buildup of intracellular inclusions inside the neurons, called Lewy bodies. Studies have shown that the Lewy bodies are made mainly of a protein called alpha-synuclein.

They are not seen in brain imaging studies but have been detected in research studies that examine the brains of people who had PD and donated their own brains to science for the purpose of research. There is no known treatment or method of removing the Lewy bodies at this time.

In PD, Lewy bodies are found in the substantia nigra as well as other areas, including the amygdala and locus coeruleus , the raphe nucleus , and the olfactory nerve . The functions controlled by these regions can be impaired in PD, although the symptoms arent as noticeable as the tremors and muscle stiffness.

Lewy bodies are also present in the brains of people who have Alzheimers disease and other types of dementia, and they are considered a sign of neurodegeneration.

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What Causes The Condition

Although there are several recognized risk factors for Parkinsons disease, such as exposure to pesticides, for now, the only confirmed causes of Parkinsons disease are genetic. When Parkinsons disease isnt genetic, experts classify it as idiopathic . That means they dont know exactly why it happens.

Many conditions look like Parkinsons disease but are instead parkinsonism from a specific cause like some psychiatric medications.

Familial Parkinsons disease

Parkinsons disease can have a familial cause, which means you can inherit it from one or both of your parents. However, this only makes up about 10% of all cases.

Experts have linked at least seven different genes to Parkinsons disease. Theyve linked three of those to early-onset of the condition . Some genetic mutations also cause unique, distinguishing features.

Idiopathic Parkinsons disease

Experts believe idiopathic Parkinsons disease happens because of problems with how your body uses a protein called -synuclein . Proteins are chemical molecules that have a very specific shape. When some proteins dont have the correct shape a problem known as protein misfolding your body cant use them and cant break them down.

With nowhere to go, the proteins build up in various places or in certain cells . The buildup of these Lewy bodies causes toxic effects and cell damage.

Induced Parkinsonism

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Genetic Forms And Genetic Risk Factors Of Pd

Frontiers

Although most cases of PD are idiopathic forms of the disease, about 15% of PD patients are recognized as having a first-degree family member with this disease. Recently, the genetic factors and gene loci involving in autosomal dominant and autosomal recessive forms of PD have been discovered due to advanced molecular genetics . The mutations in several genes, including -syn, LRRK2, PINK1, Parkin, DJ-1, VPS35 and GBA1 are linked to PD . In addition to mutations in these genetic loci, polymorphisms, and trinucleotide repeats are recognized as PD genes, or susceptibility factors for PD .

TABLE 1. Autosomal recessive and X-linked genes involved in Parkinsons disease.

TABLE 2. Autosomal dominant genes involved in Parkinsons disease.

TABLE 3. Susceptibility factors of Parkinsons disease.

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Characteristics Of The Study Population

After exclusion of individuals with missing data or outliers, 503,497 participants were available for the present analyses. Among these participants, 603 had an incident PD event. Analyses of the associations of CVD risk factors with PD were restricted to the 480,950 participants with no prior history of CVD and included 521 PD cases . The mean duration of follow-up was 9 years in all participants.

Overall, 59.2% of participants were women, 56.0% lived in rural regions, 57.3% had an income less than or equal to 19,999 yuan, and 50.8% had a primary school education or lower. Mean age of PD cases was older than that of the general population , and cases had a lower level of education . Likewise, a higher proportion of PD cases were agricultural workers or were retired compared with the general population .

Most participants were never regular drinkers or occasional drinkers . However, PD cases reported lower mean levels of physical activity than all participants . While 61.2% of men were current smokers, only 5% of women smoked, hence, analyses of smoking were restricted to men. At baseline 5.9% of all participants had diabetes, 32% were overweight or obese , and 33.5% had hypertension.

Impact On Families And Carers

Informal carers spendmany hours dailyproviding care for people living with PD.This can be overwhelming. Physical, emotional and financial pressures can cause great stress to families and carers, and support is required from the health, social, financial and legal systems. Useful support resources from other conditions can be drawn upon, such as WHOs iSupport programme for dementia.

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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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Literature Selection Data Extraction And Methodological Quality Assessment

Understanding Parkinsons Disease

Two review authors independently screened all of the citations for potentially eligible articles and extracted information from each included SR. Any conflicts were resolved through discussion, by referring to the original publication, or by consulting a third senior author.

The following information was extracted from each included SR: characteristics of the SR, including the first authors name, year of publication, and the number of included studies and participants characteristics of the original studies included in SRs, such as study design, the studied risk factor, methods used for exposure assessment, diagnostic criteria for PD, follow-up duration of cohort studies, and risk of bias details on participants characteristics, including age, sex, and region pooled effect estimation for each risk factor with the corresponding 95%confidence interval , and results from subgroup meta-analyses.

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Positron Emission Tomography Scan

The PET scan radiotracers emit electron anti-particles that are positively charged with the same mass as an electron. The presence of presynaptic DAT in dopaminergic neurons of striatum and SN can be assessed with 18F and/or 11C radiolabeled dopamine analogs. These DAT radioligands include 18F-dopamine , 18F-FE-PE2I , 18F–CFT , 18F-LBT999 , and11C-methylphenidate. The VMAT2 quantification is also possible by using either 11C or 18F radiolabeled dihydrotetrabenazine . Because of dopaminergic cell loss and subsequent loss of VMAT2, the PET signal of radiolabeled DTBZ is lower in PD patients than in controls. Both DAT and VMAT2 radioligands can detect the early signs of dopaminergic damage, although PD may not be differentiated from atypical Parkinsonism with dopaminergic dysfunction. 11C-MP4A is another PET radiotracer that monitors the level of acetylcholinesterase activity. AChE hydrolyses deactivates Ach and terminates the signal. Impairment of cholinergic system and reduction of cortical AChE has been assessed by 11C-MP4A-PET scan. AChE activity reduces more in PDD than in PD, indicating that cholinergic dysfunction is correlated with dementia in PD .

Ological Quality Of Included Systematic Reviews

Overall, none of the included SRs were judged to be of high or moderate quality with the AMSTAR-2. Seven SRs were judged to be of low methodological quality, while the remaining 39 were judged to be of critically low quality. Details regarding the methodological quality of the included SRs are shown in Fig. 2. The included SRs had relatively better performance on two out of the seven critical items, with more than 60%of the SRs rated positive for the following: used appropriate methods for statistical combination of the results , carried out an adequate investigation of publication bias and discussed its likely impact on the results of the SRs . The included SRs generally had poor performance for the remaining five critical items, with less than 30%of SRs rated positive for the following: only 2 provided a list of excluded studies, justified the exclusions, and used a satisfactory technique to assess the risk of bias in individual studies included in the review 4 registered a protocol and used a comprehensive literature search strategy, and 11 accounted for the risk of bias of individual studies when interpreting or discussing the results of the 1ptreview.

Fig. 2

The methodological quality of the 46 included systematic reviews based on AMSTAR-2 tool.

Note: AMSTAR-2 tool: Assessing the Methodological Quality of Systematic Reviews 2 tool.

Item 1: Did the research questions and inclusion criteria for the review include the components of PICO?

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Characteristics Of Included Systematic Reviews

The 46 SRs were published between 2011 and 2020, and all were published in English. The characteristics of these SRs are shown in Table 1.

Table 1

Main characteristics of included systematic reviews with meta-analysis on risk factors for the development of Parkinsons disease

CC, case -control study Co, cohort study CS, cross-sectional study NA, not applicable NCC, nested case-control study NR, not reported RCT, randomized controlled trial. aMedian follow up duration is only applicable to the included cohort studies. b1=UK Parkinsons Disease Society Brain Bank clinical diagnostic criteria 2=Clinical Diagnosis Standard proposed by China 3=Physician-confirmed diagnosis or hospital records or from database 4=International classification of disease code or other code, primary care or death certificates 5=Questionnaires or self-reported 6=Direct interview 7=Diagnosed according to cardinal signs of Parkinsons Disease. cDetailed description could be found in Table 2 and Supplementary Table 1. dTotal number and total proportion of male. eThe denominators are 74 and 39 respectively.

What Causes Parkinsons Disease

Android Parkinson

Parkinsons disease is a chronic, progressive neurological disease that currently affects about 1 million Americans. Parkinsons disease involves a small, dark-tinged portion of the brain called the substantia nigra. This is where you produce most of the dopamine your brain uses. Dopamine is the chemical messenger that transmits messages between nerves that control muscle movements as well as those involved in the brains pleasure and reward centers. As we age, its normal for cells in the substantia nigra to die. This process happens in most people at a very slow rate.

But for some people, the loss happens rapidly, which is the start of Parkinsons disease. When 50 to 60 percent of the cells are gone, you begin to see the symptoms of Parkinsons.

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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.

Comparing Risk Factors Of Incident Pd And Coronary Events

With respect to the effects of the risk factors, the differences between PD and coronary events are shown in Table and Fig. . Smoking and LDL were positively associated with risk of coronary events but were inversely associated with risk of PD . Hypertension, lipid-lowering drugs, BMI, ApoB/ApoA1 ratio, and ApoB were positively associated with the risk of coronary events but were not associated with PD . In addition, ApoA1 was inversely associated with the risk of coronary events but was not associated with PD . By contrast, age, male sex, diabetes, NLR, and FBG were common risk factors for coronary events and PD .

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Search Strategy And Eligibility Criteria

This overview of SRs has been registered on PROSPERO . An SR on non-genetic risk factors for PD was included if it met all of the following criteria: 1) at least one risk factor for PD development had been investigated 2) the study design of included primary studies was clearly stated 3) at least one meta-analysis had been conducted to quantitatively synthesize the association between the risk factor and PD development.

An SR was excluded if it 1) focused on genetic factors involved in PD development 2) included animal studies or 3) was a commentary, editorial, letter, reply, protocol, or withdrawn article. When more than one SR with meta-analysis focused on the same factor, we compared the results to determine the consistency of qualitative conclusions. If the results were consistent, for example, if all indicated it was a protective factor for PD development, we retained the SR that included the largest number of original studies. Otherwise, all versions were kept to allow us to explore the reasons behind the inconsistency.

A comprehensive literature search was conducted using Medline, Embase, and PsycINFO through the Ovid platform from January 2011 to June 2020 without language restrictions. Specialized search filters were used to identify SRs , and we manually checked the reference lists of the included SRs for any others that may have been missed. The detailed search strategies are described in the Supplementary Material.

What Role Do Genes Play

Pharmacology [CNS] 2- What is Parkinson’s Disease ? Symptoms, Causes & Risk Factors, and Treatment

Your genes are like your bodys 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 youre more likely to get a certain disease.

There are several genetic mutations that can raise your risk for Parkinsons, 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 doesnt mean youll get Parkinsons. Some people will, but many wont, and doctors dont know why. It may have to do with other genes or something in your environment.

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Medications And Parkinson’s Symptoms

Taking certain medicationsspecifically ones that block the action of dopaminecould cause Parkinson’s disease symptoms. It’s a condition called drug-induced parkinsonism, and while it isn’t Parkinson’s disease itself, it can look and feel a lot like it.

Here are some of the drugs that can cause Parkinson’s disease symptoms:

  • Anti-nausea medications
  • Drugs that treat hyperkinetic movement disorders

Keep in mind that even though these medications could cause symptoms similar to Parkinson’s, they don’t cause the disease itself. And most of the time, the symptoms go away within hours or days once you stop taking that drug, per the Parkinson’s Disease Society.

In some cases, the Parkinson’s symptoms don’t go away after a person stops taking the medication that led to them, and they’re eventually diagnosed with Parkinson’s disease.

Researchers don’t think that the medication was the cause of Parkinson’s in those cases, but that those individuals’ dopamine levels were already depleted, and the side effects of the drugs revealed their underlying Parkinson’s disease. Put another way, the medication was the “straw that broke the camel’s back,” according to the American Parkinson Disease Association.

Research on what causes Parkinson’s disease continues to grow. If you experience symptoms of Parkinson’s, such as a hand tremor, slowed movement, balance problems, or changes in your speech or writing, connect with a doctor to diagnose the condition.

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