Lifestyle Factors And Parkinsons Disease Risk In A Rural New England Case
Angeline S. AndrewAcademic Editor: Received
Abstract
Introduction. Parkinsons disease is an age-related neurodegenerative disease likely caused by complex interactions between genetic and environmental risk factors. Exposure to pesticides, toxic metals, solvents, and history of traumatic brain injury have been implicated as environmental risk factors for PD, underscoring the importance of identifying risk factors associated with PD across different communities. Methods. We conducted a questionnaire-based case-control study in a rural area on the New Hampshire/Vermont border, enrolling PD patients and age- and sex-matched controls from the general population between 2017 and 2020. We assessed frequent participation in a variety of recreational and occupational activities and surveyed potential chemical exposures. Results. Suffering from head trauma or a concussion prior to diagnosis was associated with a fourfold increased risk of PD. Adjustment for head trauma negated any risk of participation in strenuous athletic activities. We observed a 2.7-fold increased risk of PD associated with activities involving lead .. Implicating these factors in PD risk favors public health efforts in exposure mitigation while also motivating future work mechanisms and intervention opportunities.
1. Introduction
Parkinsons Disease Treatment Guidelines
An update of the Parkinsons Disease treatment Guidelines was commissioned by the European Academy of Neurology and the European section of the Movement Disorder Society. Although these treatments are initiated usually in specialized centers, the general neurologist should know the therapies and their place in the treatment pathway.
Grading of Recommendations Assessment, Development, and Evaluation methodology was used to assess the spectrum of approved interventions including deep brain stimulation or brain lesioning with different techniques . Continuous delivery of medication subcutaneously or through percutaneous ileostomy ) was also included. Changes in motor features, health-related quality of life , adverse effects, and further outcome parameters were evaluated. Recommendations were based on high-class evidence and graded in three gradations. If only lower class evidence was available but the topic was felt to be of high importance, a clinical consensus of the guideline task force was gathered.
Evidence for invasive therapies in PD is heterogeneous. Only some of these therapies have a strong scientific basis 1) 2).
European Academy of Neurology/Movement Disorder Society-European Section Guidelines on Pallidotomy for Parkinsons Disease 3).
Support For People Living With Parkinsons Disease
While the progression of Parkinsons is usually slow, eventually a persons daily routines may be affected. Activities such as working, taking care of a home, and participating in social activities with friends may become challenging. Experiencing these changes can be difficult, but support groups can help people cope. These groups can provide information, advice, and connections to resources for those living with Parkinsons disease, their families, and caregivers. The organizations listed below can help people find local support groups and other resources in their communities.
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Mitochondrial Dysfunction And Oxidative Stress Related Biomarkers
Urate
Protein DJ-1
Additionally, Lin et al. have showed that the level of blood DJ-1 modified by 4-hydroxy-2-nonenal is significantly decreased in late-stage PD patients, suggesting that 4-HNE modified DJ-1 may potentially be one of the biomarkers of disease severity in the body fluid. The oxidized DJ-1 is promising to be a useful biomarker .
Coenzyme Q10
8-Hydroxydeoxyguanosine
Advanced Oxidized Protein Products
Advanced oxidized protein products is a reliable biomarker of halogenative stress, and protein halogenation is a kind of oxidative stress induced by phagocytic overstimulation. When quantifying AOPP concentrations with enzyme-linked immunosorbent assays , researchers find that AOPP levels in serum of PD patients are significantly higher than control subjects. But there is no significant difference in CSF AOPP levels, because basal CSF levels are very low in all individuals. In addition, it has been demonstrated that the higher the Hoehn-Yahr stage or levodopa dose in PD patients or the longer the disease duration, the lower the serum AOPP levels . So AOPP will play an important role in diagnosis of PD and monitoring disease progression.
Levodopa Usually Is Best First Therapy For Motor Symptoms Neurology Group Says
byJudy George, Senior Staff Writer, MedPage Today November 15, 2021
Neurologists should counsel people with early Parkinson’s disease about the benefits and risks of starting treatment with levodopa, dopamine agonists, or monoamine oxidase B inhibitors for motor symptoms, new guidelines from the American Academy of Neurology stated.
If treatment is started, levodopa is the preferred initial therapy for most early Parkinson’s patients, wrote Tamara Pringsheim, MD, of the University of Calgary in Alberta, Canada, and co-authors in Neurology.
“We carefully reviewed the available research on the effectiveness and possible risks of medications to treat motor symptoms in people with early Parkinson’s disease and found that levodopa is usually the best first treatment for these symptoms,” Pringsheim said in an AAN statement.
“Still, there are side effects with levodopa as well as other drugs, so it is important that a person newly diagnosed with Parkinson’s disease discusses all options with their neurologist before deciding on the best treatment plan for them,” she added.
The guidelines update AAN practice parameters from 2002. Since then, new medications and new formulations of older medications have become available, Pringsheim and colleagues noted.
The analysis showed:
- Levodopa was better at reducing motor symptoms than dopamine agonists, with most studies demonstrating significantly greater improvement in UPDRS part III scores for up to 5 years of follow-up
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Rapid Eye Movement Sleep Behaviour Disorder
REM sleep behaviour is associated with PD and is a prodromal symptom in many cases. Patients with REM sleep disorder often physically act out vivid dreams during REM sleep, which can affect their quality of life and that of their family and carers. NICE recommends the off-label use of clonazepam or melatonin . Benzodiazepines are cautioned in the elderly population therefore, this patient cohort must be monitored closely by their care team if started on clonazepam.
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Treating Parkinsons With Complementary Medicine
Complementary medicine incorporates many different practices that can be used alongside conventional medicine to try to ease PD symptoms. There is typically not as much rigorous data to support the use of complementary medicine techniques, as compared to conventional medicine, but many patients find them helpful. These include yoga and massage.
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Dysfunctional Protein Clearance Systems
There are two central protein clearance systems within cells responsible for the removal of dysfunctional proteins: the ubiquitin-proteasome system and the autophagy-lysosome pathway. The UPS is primarily responsible for breaking down abnormal proteins, and it does so by tagging them with ubiquitin and transporting them to the proteasome for degradation. The autophagy-lysosome pathway is divided into three constituents: macroautophagy, microautophagy, and chaperone-mediated autophagy . Briefly, in macroautophagy, intracellular components, including cytosolic proteins, are engulfed by the autophagosome, which then fuses with the lysosome, leading to the breakdown of its contents. On the other hand, in microautophagy, the lysosome alone engulfs and destroys cytoplasmic components. CMA is a more selective process, whereby molecular chaperones target specific proteins and transport them to the lysosome for degradation . Monomeric -synuclein is generally cleared by both the UPS and the autophagy-lysosome pathway , and damage in either of their machineries is implicated in the pathogenesis of PD by contributing to the accumulation of defective proteins, in particular soluble misfolded -synuclein .
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Therapeutic And Formalized Pattern Exercises
The SPARX study enrolled 128 de novo patients and compared high- and moderate-intensity treadmill exercises with a wait-list control group. After six month of 3 days per week exercise, the results showed that the high-intensity group, who exercised at 80 to 85% maximum heart rate, had less change in motor symptoms compared with the usual care group9898. Schenkman M, Moore CG, Kohrt WM, Hall DA, Delitto A, Comella CL, et al. Effect of high-intensity treadmill exercise on motor symptoms in patients with de novo Parkinson disease: a phase 2 randomized clinical trial. JAMA Neurol. 2018 Feb 1 75:219-26. https://doi.org/10.1001/jamaneurol.2017.3517 . The Park-in-shape trial , a home-based study, recruited 130 PD patients in Hoehn & Yahr stage 2 who were randomized either to exercise on a stationary cycle or stretching at least three times per week. After the 6-month program, the MDS-UPDRS motor score change was smaller in the aerobic group, resulting in a between-group adjusted mean difference of 4.2 points favoring the cycling group9999. Van der Kolk NM, de Vries NM, Kessels RPC, Joosten H, Zwinderman AH, Post B, et al. Effectiveness of home-based and remotely supervised aerobic exercise in Parkinsons disease: a double-blind, randomised controlled trial. Lancet Neurol. 2019 Nov 1 18:P998-1008. https://doi.org/10.1016/S1474-442230285-6 .
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Deep Brain Stimulation For The Treatment Of Pd Patients
Current surgical indications for PD include reducing motor fluctuations, off time, dyskinesias, tremor, and improvement of levodopa-responsive symptoms. Deep brain stimulation is probably the most critical advance in treatment of PD since the introduction of levodopa. The beneficial effects of DBS on motor symptoms and quality of life in advanced PD have been shown in randomized, controlled studies6666. Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schäfer H, Bötzel K, et al. A randomized trial of deep-brain stimulation for Parkinsons disease. N Engl J Med. 2006 Aug 31 355:896-908. https://doi.org/10.1056/NEJMoa060281 ,6767. Williams A, Gill S, Varma T, Jenkinson C, Quinn N, Mitchell R, et al. Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinsons disease : a randomised, open-label trial. Lancet Neurol. 2010 Jun 1 9:P581-91. https://doi.org/10.1016/S1474-442270093-4 .
Pathophysiology And Presenting Features
Classic presenting features of PD include motor symptoms, such as bradykinesia, rigidity, rest tremor and postural instability. However, non-motor symptoms, such as depression, cognitive impairment, pain and autonomic disturbances, are also often present and they can severely affect a patients quality of life. There are several information sheets available for patients that cover the management of multiple common types of pain in PD.
The motor symptoms are largely caused by the progressive loss of dopaminergic neurons in the substantia nigra compacta, which ultimately reduces dopaminergic input to the striatum and other brain regions. Compensatory mechanisms in the brain are so effective that the clinical symptoms of PD may only develop when around 80% of dopaminergic neurons have degenerated. By contrast, the Braak theory of PD suggests that the disease process starts in the olfactory bulb and lower part of the medulla, and it is not until stage 3 that the substantia nigra becomes involved in the process. There is also direct evidence of Parkinson pathology being spread from the gastrointestinal tract to the brain in rodents. There are therapeutic implications of gut involvement it is known that swallowing and the stomach are the two main problems of PD therapy and lead to the use of non-oral therapies.
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When To Start Treatment
Deciding when to start drug therapy for Parkinsons disease should be individually tailored to a patients symptoms, circumstances and comorbidities. Treatment is indicated when symptoms impact on quality of life. When treatment is needed there is no evidence to support undue delay because of concerns about levodopa toxicity or the development of treatment resistance.3 The aim is to control symptoms and maintain an on state.
Some drugs with good symptomatic benefit are speculated to have a role in neuroprotection and some specialists advocate their use from the time of diagnosis.4 Delayed start trials have been used to try and differentiate symptomatic from disease-modifying effects. A recent delayed start study of rasagiline, a monoamine oxidase B inhibitor, in treatment-naïve patients with mild Parkinsons disease showed a small benefit in the low-dose treatment group. This was not seen with the 2 mg dose and a clear explanation for this has not been established.5 Further studies are needed before such treatments are considered truly disease modifying. Until a drug is unequivocally proven to slow disease progression, the time to commence treatment will remain contentious.
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A New Era For Parkinsons Disease Treatment
March 2, 2022 | By
A non-invasive ultrasound treatment for Parkinsons disease that was tested in a pivotal trial led by University of Maryland School of Medicine researchers is now broadly available at the University of Maryland Medical Center .
Howard Eisenberg, MD, Dheeraj Gandhi, MD, MBBS, Paul Fishman, MD, PhD, Bert W. OMalley, MD.
The device, called Exablate Neuro, was approved in November by the U.S. Food and Drug Administration to treat advanced Parkinsons disease on one side of the brain. The approval was based on findings from the UMSOM clinical trial and effectively expands access to focused ultrasound beyond clinical trial participation.
Rapid Reversal of Symptoms
Focused ultrasound is an incisionless procedure, performed without the need for anesthesia or an in-patient stay in the hospital. Patients, who are fully alert, lie in a magnetic resonance imaging scanner, wearing a transducer helmet. Ultrasonic energy is targeted through the skull to the globus pallidus, a structure deep in the brain that helps control regular voluntary movement. MRI images provide doctors with a real-time temperature map of the area being treated. During the procedure, the patient is awake and providing feedback, which allows doctors to monitor the immediate effects of the tissue ablation and make adjustments as needed.
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A New Era for Parkinsons Disease Treatment
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The Next Generation Of Trials
Studer was part of the initial studies involving fetal tissue in the 1980s and 1990s, and knew from the start that the work was more of a proof of principle than a solution for people with Parkinsons. For me it was clear that a fetal transplant isnt a long-term solution because of ethical, legal and practical issues. Because this procedure requires 4 to 12 fetuses per patient, there was no way they could treat thousands, let alone tens of thousands, of people that way. Instead, Studer turned to stem cells.
Immunosuppression is a particularly important element of BlueRocks approach, because it relies on a single cell line that cannot be adjusted to more closely resemble the recipients own tissues. A group led by stem-cell scientist and neurosurgeon Jun Takahashi at Kyoto University in Japan is attempting to provoke a lesser immune response by pairing transplant recipients with cells that are less likely to be rejected. The researchers are using cell-surface proteins, called major histocompatibility complexes , that are recognized by the adaptive immune system and can have varying levels of compatibility from one person to another. Rather than using frozen cell lines, Takahashi and his colleagues are creating a fresh batch of MHC-matched cells for each transplant.
Latest Treatments For Parkinsons Disease
Researchers still have much to learn about Parkinsons disease. As researchers continue to work hard in the fight against this disease, the lessons they learn may lead to new, innovative treatments.
Parkinsons disease is a neurodegenerative disorder that affects dopaminergic neurons in the substantia nigra area of the brain, advises the Parkinsons Foundation. Even though the disease itself is not fatal, PD is a serious condition one which the Centers for Disease Control and Prevention rates as the 14th most common cause of death in the United States due to the diseases related complications.
PD symptoms affect autonomous functions and the ability to move limbs. The Mayo Clinic notes that most people with PD may show little or no expression, speech may become slurred, arms may not swing when one walks, and stiffness and gait issues may become apparent. PD can affect balance and posture as well.
There is no cure for PD, but there are many different treatments that can slow its progress and reduce symptoms.
WebMD says new treatments for PD give individuals continued hope. Heres a look at some of the potential options.
Stem cell usagetem cells can turn into any type of cell, and there is hope that they can transform into the dopamine-producing neurons used to treat PD. But there is increased risk of involuntary movement from too much dopamine with this treatment. Stem cell therapy also may present ethical and moral issues with some patients.
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Manual Therapy And Exercise
Chiropractic manipulation, osteopathic manipulation, and Trager therapy have been suggested to benefit patients with Parkinsons disease. No studies exist, however, to refute or confirm this position. The Alexander technique has shown some benefit and patient improvement has been noted in some studies.
Standard physical therapy, as well as occupational therapy, did result in improved functional outcomes, but the benefit was small and was not sustained when the exercise therapy stopped.
How Is It Treated And Is There A Cure
For now, Parkinsons disease is not curable, but there are multiple ways to manage its symptoms. The treatments can also vary from person to person, depending on their specific symptoms and how well certain treatments work. Medications are the primary way to treat this condition.
A secondary treatment option is a surgery to implant a device that will deliver a mild electrical current to part of your brain . There are also some experimental options, such as stem cell-based treatments, but their availability often varies, and many arent an option for people with Parkinsons disease.
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Editorial Note On The Review Process
F1000 Faculty Reviews are commissioned from members of the prestigiousF1000 Faculty and are edited as a service to readers. In order to make these reviews as comprehensive and accessible as possible, the referees provide input before publication and only the final, revised version is published. The referees who approved the final version are listed with their names and affiliations but without their reports on earlier versions .
The referees who approved this article are:
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Fredric P. Manfredsson, Parkinsons Disease Research Unit, Department of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona, USA
No competing interests were disclosed.
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Tipu Z. Aziz, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
No competing interests were disclosed.