Parkinson's disease

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improving gait speed, the base of support, stride length, and trunk and arm-swing movement. Strategies include using assistive equipment (pole walking and treadmill walking), verbal cueing (manual, visual, and auditory), exercises (marching and PNF patterns), and altering environments (surfaces, inputs, open vs. closed). Strengthening exercises have shown improvements in strength and motor function for people with primary muscular weakness and weakness related to inactivity with mild to moderate PD, but reports show an interaction between strength and the time the medications were taken. Therefore, people with PD should perform exercises 45 minutes to one hour after medications when they are capable. Deep diaphragmatic breathing exercises are beneficial in improving chest-wall mobility and vital capacity decreased by a forward flexed posture and respiratory dysfunctions in advanced PD. Exercise may improve constipation. Whether exercise reduces physical fatigue in PD remains unclear.

1983: 3702: 3587: 1526: 3153: 3711: 1517: 2026:. The Queen Square Brain Bank criteria require slowness of movement (bradykinesia) plus either rigidity, resting tremor, or postural instability. Other possible causes of these symptoms need to be ruled out. Finally, three or more of the following supportive symptoms are required during onset or evolution: unilateral onset, tremor at rest, progression in time, asymmetry of motor symptoms, response to levodopa for at least five years, the clinical course of at least ten years and appearance of dyskinesias induced by the intake of excessive levodopa. Assessment of 1951:(BBB) and release more proinflammatory cytokines, like interferon-γ (IFNγ), TNFα, and IL-1β. Mast cell degranulation and subsequent proinflammatory cytokine release is implicated in BBB breakdown in PD. Another immune cell implicated in PD are peripheral monocytes and have been found in the substantia nigra of people with PD. These monocytes can lead to more dopaminergic connection breakdown. In addition, monocytes isolated from people with Parkinson's disease express higher levels of the PD-associated protein, LRRK2, compared with non-PD individuals via 2458:, due to its notable risk of complications. However, levodopa-related dyskinesias still correlate more strongly with the duration and severity of the disease than the duration of levodopa treatment. A careful consideration of the risks and benefits of starting treatment is crucial to optimize patient outcomes. In the middle stages of Parkinson's disease, the primary aim is to reduce patient symptoms. Episodes of medication overuse or any sudden withdrawals from medication must be promptly managed. If medications prove ineffective, surgery (such as 134: 69: 3013:, prognistication can be difficult and prognoses can be highly variable. On average, life expectancy is reduced in those with Parkinson's, with younger age of onset resulting in greater life expectancy decreases. Although PD subtype categorization is controversial, the 2017 Parkinson's Progression Markers Initiative study identified three broad scorable subtypes of increasing severity and more rapid progression: mild-motor predominant, intermediate, and diffuse malignant. Mean years of survival post diagnosis were 20.2, 13.1, and 8.1. 2186: 3057: 703: 14020: 2812:. DBS of the globus pallidus interna improves motor function, while DBS of the thalamic DBS improves tremor, but has little impact on bradykinesia or rigidity. DBS of the subthalamic nucleus is usually avoided if a history of depression or neurocognitive impairment is present. DBS of the subthalamic nucleus is associated with a reduction in medication. Pedunculopontine nucleus DBS remains experimental at present. Generally, DBS is associated with 30–60% improvement in motor score evaluations. 2715:, an enzyme that breaks down dopamine. They have been found to help alleviate motor symptoms when used as monotherapy (on their own); when used in conjunction with levodopa, time spent in the off phase is reduced. Selegiline has been shown to delay the need for beginning levodopa, suggesting that it might be neuroprotective and slow the progression of the disease. An initial study indicated that selegiline in combination with levodopa increased the risk of death, but this has been refuted. 712: 1212: 3144: 3556: 3429: 3381: 2511: 81: 3716: 3715: 3712: 2765: 3717: 107: 3230: 3714: 2269: 3471: 95: 2591:

state"), and phases with poor response to medication and increased PD symptoms ("off state"). Using lower doses of levodopa may reduce the risk and severity of these levodopa-induced complications. A former strategy, called "drug holidays", to reduce levodopa-related dyskinesia and fluctuations was to withdraw levodopa medication for some time, which can bring on dangerous side-effects such as

2608: 2797:, which sends electrical impulses to specific parts of the brain. DBS is recommended for people who have PD with motor fluctuations and tremor inadequately controlled by medication, or to those who are intolerant to medication lacking severe neuropsychiatric problems. Other less common surgical therapies involve intentional formation of lesions to suppress overactivity of specific 2550: 2170:(CBS). PSP predominantly involves rigidity, early falls, bulbar symptoms, and vertical gaze restriction; it can be associated with frontotemporal dementia symptoms. CBS involves asymmetric parkinsonism, dystonia, alien limb, and myoclonic jerking. Presentation timelines and associated symptoms can help differentiate similar movement disorders from idiopathic Parkinson disease. 2014:

and ruled out appropriately to begin a different treatment and disease progression (anti-Parkinson's medications are typically less effective at controlling symptoms in Parkinson-plus syndromes). Faster progression rates, early cognitive dysfunction or postural instability, minimal tremor, or symmetry at onset may indicate a Parkinson-plus disease rather than PD itself.

3663:(COMT – the enzyme that converts L-DOPA to dopamine). No safety concerns have been reported but the approaches have largely failed in phase two clinical trials. The delivery of GAD showed promise in phase two trials in 2011, but while effective at improving motor function, was inferior to DBS. Follow-up studies in the same cohort have suggested persistent improvement. 2631:. Tolcapone has been available for but its usefulness is limited by possible liver damage complications requiring liver-function monitoring. Entacapone and opicapone cause little alteration to liver function. Licensed preparations of entacapone contain entacapone alone or in combination with carbidopa and levodopa. Opicapone is a once-daily COMT inhibitor. 1084:. It is associated with dopaminergic drugs used to treat the motor symptoms, higher morbidity, mortality, a decrease in health-promoting behaviors, and longer nursing home stays. Additionally, it correlates with depression and may herald onset of dementia in advanced stages. Unlike other psychotic forms, PDP typically presents with a clear 1019:. Some of them, such as depression and anxiety, are known to precede characteristic motor signs by up to several years and may herald the development of PD, while most of them worsen as the disease progresses. Research indicates that patients with more severe motor symptoms are at higher risk for any NPS. Conversely, NPS can worsen PD. 2935:. In advanced stages, additional intake of low-protein products such as bread or pasta is recommended for similar reasons. To minimize interaction with proteins, levodopa should be taken 30 minutes before meals. At the same time, regimens for PD restrict proteins during breakfast and lunch, allowing protein intake in the evening. 2691:) are useful for people in the initial stages and possibly to control off states in those in advanced states. Due to an increased risk of cardiac fibrosis with ergot-derived dopamine agonists (bromocriptine, cabergoline, dihydroergocryptine, lisuride, and pergolide), they should only be considered for adjunct therapy to levodopa. 855:, and secondarily to bone fractures, thus, reduced mobility and quality of life. PI is absent in the initial stages and usually occurs 10–15 years after first diagnosis. Within the first three years after disease onset, PI may indicate atypical parkinsonism. Together with bradykinesia and rigidity, it is responsible for the 3210:—began expanding Parkinson's description, adding bradykinesia as one of the four cardinal symptoms. In 1877, Charcot renamed the disease after Parkinson, as not all patients displayed the tremor suggested by "shaking palsy". Subsequent neurologists who made early advances to the understanding of Parkinson's include 2919:(prolonged emptying of stomach contents). A balanced diet, based on periodical nutritional assessments, is recommended, and should be designed to avoid weight loss or gain and minimize the consequences of gastrointestinal dysfunction. As the disease advances, swallowing difficulties (dysphagia) may appear. Using 3419:

A study based on 2017 data estimated the US economic PD burden at $ 51.9 billion, including direct medical costs of $ 25.4 billion and $ 26.5 billion in indirect and non-medical costs. The projected total economic burden surpasses $ 79 billion by 2037. These findings highlight the

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Relative to Europe and North America, disease prevalence is lower in Africa—especially sub-Saharan Africa—but similar in Latin America. Although China is predicted to have nearly half of the global Parkinson's population by 2030, estimates of prevalence in Asia have varied. Potential explanations for

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techniques. As for gait and addressing the challenges associated with the disease such as hypokinesia, shuffling, and decreased arm swing, physiotherapists have a variety of strategies to improve functional mobility and safety. Areas of interest concerning gait during rehabilitation programs focus on

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Treating motor symptoms with surgery was once a common practice but the discovery of levodopa has decreased the amount of procedures. Studies have led to great improvements in surgical techniques, so surgery can be used in people with advanced PD for whom drug therapy is no longer sufficient. Surgery

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Though dopamine agonists are less effective than levodopa at controlling PD motor symptoms, they are effective enough to manage these symptoms in the first years of treatment. Dyskinesias due to dopamine agonists are rare in younger people who have PD, but along with other complications, become more

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Levodopa and proteins use the same transportation system in the intestine and the blood–brain barrier, thereby competing for access. Taking them together results in reduced effectiveness of the drug. Therefore, when levodopa is introduced, excessive protein consumption is discouraged in favour of a

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During the course of PD, affected people can experience a wearing-off phenomenon, where a recurrence of symptoms occurs after a dose of levodopa, but right before their next dose. Catechol-O-methyltransferase (COMT) is a protein that degrades levodopa before it can cross the blood–brain barrier and

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are dopa decarboxylase inhibitors that fail to cross the blood–brain barrier and inhibit the conversion of levodopa to dopamine outside the brain, reducing side-effects and improving the availability of levodopa for passage into the brain. One of these drugs is usually taken along with levodopa and

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Multiple causes can occur for parkinsonism or diseases that look similar. Stroke, certain medications, and toxins can cause "secondary parkinsonism" and need to be assessed during visit. Parkinson-plus syndromes, such as progressive supranuclear palsy and multiple system atrophy, must be considered

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For some people with PD, masked facial expressions and difficulty moderating facial expressions of emotion or recognizing other people's facial expressions can impact social well-being. As the condition progresses, tremor, other motor symptoms, difficulty communicating, or issues with mobility may

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Dopamine agonists produce side effects, including drowsiness, hallucinations, insomnia, nausea, and constipation. Side effects appear with minimal clinically effective doses giving the physician reason to search for a different drug. Agonists have been related to impulse-control disorders (such as

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with or without physical therapy can be beneficial to maintain and improve mobility, flexibility, strength, gait speed, and quality of life. When an exercise program is performed under the supervision of a physiotherapist, more improvements occur in motor symptoms, mental and emotional functions,

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may be useful as treatment of motor symptoms, but evidence for use is lacking. Anticholinergics should not be used for dyskinesia or motor fluctuations but may be considered topically for drooling. A diverse range of symptoms beyond those related to motor function can be treated pharmaceutically.

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Activated microglia influence the activation of astrocytes, converting their neuroprotective phenotype to a neurotoxic one. Astrocytes in healthy brains serve to protect neuronal connections. In Parkinson's disease, astrocytes cannot protect the dopaminergic connections in the striatum. Microglia

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In contrast to other neurodegenerative disorders, many Parkinson's symptoms can be attributed to the loss of a single cell type: mesencephalic dopaminergic (DA) neurons. Consequently, DA neuron regeneration is a promising therapeutic approach. Although most initial research sought to generate DA

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In improving flexibility and range of motion for people experiencing rigidity, generalized relaxation techniques such as gentle rocking have been found to decrease excessive muscle tension. Other effective techniques to promote relaxation include slow rotational movements of the extremities and

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Dopamine agonists that bind to dopamine receptors in the brain have similar effects to levodopa. These were initially used as a complementary therapy to levodopa for individuals experiencing levodopa complications (on-off fluctuations and dyskinesias); they are mainly used on their own as first

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that primes the human immune system to destroy alpha-synuclein, PD01A, entered clinical trials and a phase one report in 2020 suggested safety and tolerability. In 2018, an antibody, PRX002/RG7935, showed preliminary safety evidence in stage I trials supporting continuation to stage II trials.

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When PD diagnoses are checked by autopsy, movement disorders experts are found on average to be 79.6% accurate at initial assessment and 83.9% accurate after refining diagnoses at follow-up examinations. When clinical diagnoses performed mainly by nonexperts are checked by autopsy, the average

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Prolonged use of levodopa is associated with the development of complications, such as involuntary movements (dyskinesias) and fluctuations in the impact of the medication. When fluctuations occur, a person can cycle through phases with good response to medication and reduced PD symptoms ("on

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and is discouraged. Most people with PD eventually need levodopa and later develop levodopa-induced fluctuations and dyskinesias. Adverse effects of levodopa, including dyskinesias, may mistakenly influence people affected by the disease and sometimes their healthcare professionals to delay

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scans. It has shown high agreement with clinical diagnoses of PD. Reduced dopamine-related activity in the basal ganglia can help exclude drug-induced Parkinsonism. This finding is nonspecific and can be seen with both PD and Parkinson-plus disorders. In the United States, DaTSCANs are only

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Exercise—one of the most common recommendations to prevent or delay Parkinson's—may exert a neuroprotective effect. In animal studies investigating the cellular basis, exercise has been found to increase neurotrophic growth factor expression and to reduce alpha-synuclein expression,

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has shown potential in distinguishing between PD and Parkinson-plus syndromes, as well as between PD motor subtypes, though its diagnostic value is still under investigation. CT and MRI are used to rule out other diseases that can be secondary causes of parkinsonism, most commonly

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The goal of palliative care is to improve quality of life for both the patient and family by providing relief from the symptoms and stress of illnesses. As Parkinson's is uncurable, treatments focus on slowing decline and improving quality of life and are therefore palliative.

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Cho SJ, Bae YJ, Kim JM, Kim D, Baik SH, Sunwoo L, et al. (March 2021). "Diagnostic performance of neuromelanin-sensitive magnetic resonance imaging for patients with Parkinson's disease and factor analysis for its heterogeneity: a systematic review and meta-analysis".

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daily living activities, and quality of life compared with a self-supervised exercise program at home. Clinical exercises may be an effective intervention targeting overall well-being of individuals with Parkinson's. Improvement in motor function and depression may happen.

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and nursing homes, while the share coming from medication was substantially lower. Indirect costs are high, due to reduced productivity and the burden on caregivers. In addition to economic costs, PD reduces quality of life of those with the disease and their caregivers.

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Levodopa is usually the first drug of choice when treating Parkinson's disease and has been the most widely used PD treatment since the 1980s. The motor symptoms of PD are the result of reduced dopamine production in the brain's basal ganglia. Dopamine fails to cross the

1650:, pars reticulata and internal globus pallidus. This reduction in inhibition allows the subthalamic nucleus to excite internal globus pallidus and pars reticulata, which in turn inhibit thalamic activity, thereby suppressing excitatory signals to the motor cortex. 3016:

Around 30% of Parkinson's patients develop dementia, and is 12 times more likely to occur in elderly patients of those with severe PD. Dementia is less likely to arise in patients with tremor-dominant PD. Parkinson's disease dementia is associated with a reduced

809:", the tendency of the index finger and thumb to touch and perform a circular movement that reminds of the early pharmaceutical technique of manually making pills. Despite it being the most noticeable sign, tremor is present in only about 70–90 percent of cases. 12892:

Volc D, Poewe W, Kutzelnigg A, Lührs P, Thun-Hohenstein C, Schneeberger A, et al. (July 2020). "Safety and immunogenicity of the α-synuclein active immunotherapeutic PD01A in patients with Parkinson's disease: a randomised, single-blinded, phase 1 trial".

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symptoms (NPS) are common and range from mild disturbances to severe impairment, comprising abnormalities in cognition, mood, behavior, or thought which can interfere with daily activities, reduce quality of life, and increase the risk for admission to a

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Exercise programs are recommended in people with PD and recent reviews (2024) have demonstrated their efficacy. Some evidence shows that speech or mobility problems can improve with rehabilitation, although studies are scarce and of low quality. Regular

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in people with PD after exercising with manual putty. Improvements in both manual dexterity and strength can have a favorable impact on people with Parkinson's disease, fostering increased independence in daily activities that require grasping objects.

833:, also referred to as rigor or "stiffness", is the increased resistance during passive mobilization of a limb affecting up to 89 percent of cases. It usually occurs after onset of tremor and bradykinesia on one or both sides of the body and can lead to 3367:

interfere with social engagement, causing individuals with PD to feel isolated. Public perception and awareness of PD symptoms such as shaking, hallucinating, slurring speech, and being off balance is lacking in some countries and can lead to stigma.

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Yan Z, Wang W, Tao X, Cheng W, Zuo G, Chen Z, et al. (November 2022). "High-dose versus low-dose inhaled levodopa (CVT-301) in patients with Parkinson disease for the treatment of OFF episodes: a meta-analysis of randomized controlled trials".

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COMT inhibitors allow for more levodopa to cross. They are normally used in the management of later symptoms, but can be used in conjunction with levodopa/carbidopa when a person is experiencing the wearing off-phenomenon with their motor symptoms.

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Palliative care should be involved earlier, rather than later, in the disease course. Palliative care specialists can help with physical symptoms, emotional factors such as loss of function and jobs, depression, fear, and existential concerns.

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has been used to reduce severe motor symptoms when drugs are ineffective. There is little evidence for treatment of the non-movement-related symptoms, such as sleep disturbances and mood instability. The average life expectancy is near-normal.

3124:, as well as agricultural regions of California, Florida, Pennsylvania, and Texas: collectively termed the "PD belt". It is hypothesized that this is due to localized environmental factors like herbicides, pesticides, and industrial waste. 10757:

Fox CM, Ramig LO, Ciucci MR, Sapir S, McFarland DH, Farley BG (November 2006). "The science and practice of LSVT/LOUD: neural plasticity-principled approach to treating individuals with Parkinson disease and other neurological disorders".

1841:; individuals at this stage may be asymptomatic or have early nonmotor symptoms (such as loss of sense of smell or some sleep or automatic dysfunction). As the disease progresses, Lewy bodies develop in the substantia nigra, areas of the 7064:

Zamanian MY, Parra RM, Soltani A, Kujawska M, Mustafa YF, Raheem G, et al. (June 2023). "Targeting Nrf2 signaling pathway and oxidative stress by resveratrol for Parkinson's disease: an overview and update on new developments".

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A 2020 Cochrane review found no certain evidence that cognitive training is beneficial for people with Parkinson's disease, dementia or mild cognitive impairment. The findings are based on low certainty evidence of seven studies.

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has emerged as the most successful medication and was approved for medical use in the United States in 2019. It is approved as an add-on treatment to the levodopa/carbidopa regime. LRRK2 kinase inhibitors are also of interest.

2209:. Differential diagnosis can be narrowed down with careful history and physical exam (especially focused on the sequential onset of specific symptoms), progression of the disease, and response to treatment. Some key symptoms: 2381:—have been proposed to be neuroprotective; animal and cell studies have shown that urate can prevent dopaminergic neurodegeneration. Although longitudinal studies observe a slight decrease in PD risk among those who consume 3436:

The birthday of James Parkinson, 11 April, has been designated as World Parkinson's Day. A red tulip was chosen by international organizations as the symbol of the disease in 2005; it represents the 'James Parkinson' tulip

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Leite Silva AB, Gonçalves de Oliveira RW, Diógenes GP, de Castro Aguiar MF, Sallem CC, Lima MP, et al. (February 2023). "Premotor, nonmotor and motor symptoms of Parkinson's Disease: A new clinical state of the art".

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Although Parkinson is typically credited with the first detailed description of PD, many previous texts reference some of the disease's clinical signs. In his essay, Parkinson himself acknowledged partial descriptions by

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is usually considered final proof that the person had PD. The clinical course of the illness over time may diverge from PD, requiring that presentation is periodically reviewed to confirm the accuracy of the diagnosis.

819:, beginning, and executing, resulting in overall slowed movement with reduced amplitude which affects sequential and simultaneous tasks. Hence, it interferes with daily activities such as dressing, feeding and bathing. 966:. All gastrointestinal features can be severe enough to cause discomfort, endanger health, and complicate disease management. Despite being related to each other, the exact mechanism of these symptoms remains unknown. 3496:

was diagnosed with PD at 29 years old, and has used his diagnosis to increase awareness of the disease. To illustrate the effects of the disease, Fox has appeared without medication in television roles and before the

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has increased, Parkinson's disease prevalence has also risen, with an estimated increase in cases by 74% from 1990 to 2016. The total number is predicted to rise to over 12 million patients by 2040. Some label this a

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Along with offering emotional support to both the affected person and family, palliative care addresses goals of care. People with PD may have difficult decisions to make as the disease progresses, such as wishes for

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Common side effects are nausea, dizziness, insomnia, sleepiness, and (in selegiline and rasagiline) orthostatic hypotension. MAO-Bs are known to increase serotonin and cause a potentially dangerous condition known as

2243:– This can at first look like parkinsonism, but has key differentiators. In essential tremor, the tremor gets worse with action (improves in PD), a lack of other symptoms is common in PD, and normal DatSCAN is seen. 1853:. These brain sites are the main places of neuronal degeneration in PD, but Lewy bodies may be protective from cell death (with the abnormal protein sequestered or walled off). Other forms of alpha-synuclein (e.g. 12583: 10493:

Dereli EE, Yaliman A (April 2010). "Comparison of the effects of a physiotherapist-supervised exercise programme and a self-supervised exercise programme on quality of life in patients with Parkinson's disease".

2687:. Secondary effects such as confusion and hallucinations are common, individuals receiving apomorphine treatment should be closely monitored. Two dopamine agonists administered through skin patches (lisuride and 15902: 15883: 15868: 2441:

classifies the degree of pathology in patients with Parkinson's disease into six stages that correlate with early, middle, and late presentations of the disease. Treatment in the first stage aims for an optimal

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to ease and standardize the diagnostic process, especially in the early stages of the disease. The most widely known criteria come from the UK Queen Square Brain Bank for Neurological Disorders and the U.S.

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About 1.5 million Americans have received a diagnosis of Parkinson's disease, but only 5 to 10 percent learn of it before age 40, according to the National Parkinson Foundation. Davis Phinney was among the

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share genetic variations and molecular pathways. Some autoimmune diseases may even increase one's risk of developing PD, up to 33% in one study. Autoimmune diseases linked to protein expression profiles of

1161:(SDB), many of which can be worsened by medication. RBD may begin years prior to the initial motor symptoms. Individual presentation of symptoms vary, although most of people affected by PD show an altered 2875:. Few studies have been conducted on the effectiveness of OT, and their quality is poor, although with some indication that it may improve motor skills and quality of life for the duration of the therapy. 12175: 2181:

is similar in cause for both vascular parkinsonism and idiopathic PD, and so present with similar symptoms. Differentiation can be made with careful bedside examination, history evaluation, and imaging.

3195:. Parkinson described three cardinal symptoms: tremor, postural instability and "paralysis" (undistinguished from rigidity or bradykinesia), and speculated that the disease was caused by trauma to the 3044:, which worsens with disease progession and can hinder communication. Additionally, over 80% of PD patients develop dysphagia: consequent inhalation of gastric and oropharyngeal secretions can lead to 10299:

Ernst M, Folkerts AK, Gollan R, Lieker E, Caro-Valenzuela J, Adams A, et al. (April 2024). "Physical exercise for people with Parkinson's disease: a systematic review and network meta-analysis".

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written by Ferenc Pápai Páriz in 1690, some 120 years before Parkinson. Although Páriz correctly described all four cardinal signs, it was only published in Hungarian and was not widely distributed.

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Moosa S, Martínez-Fernández R, Elias WJ, Del Alamo M, Eisenberg HM, Fishman PS (September 2019). "The role of high-intensity focused ultrasound as a symptomatic treatment for Parkinson's disease".

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PD, in a narrow sense, can be seen as a genetic disease; heritability is estimated to lie between 22 and 40 percent, across different ethnicities. Around 15 percent of diagnosed individuals have a

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Gene therapy typically involves the use of a noninfectious virus to shuttle genetic material into a part of the brain. Approaches have involved the expression of growth factors to prevent damage (

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Hitti FL, Yang AI, Gonzalez-Alegre P, Baltuch GH (September 2019). "Human gene therapy approaches for the treatment of Parkinson's disease: An overview of current and completed clinical trials".

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Both fetal and iPSC-derived DA neurons have been transplanted into patients in clinical trials. Although some patients see improvements, the results are highly variable. Adverse effects, such as

2403:. Certain medications may also be used to provide symptomatic relief and improve the patient's quality of life. The medications used in Parkinson's disease work by either increasing endogenous 8232:"The diagnostic accuracy of dopamine transporter SPECT imaging to detect nigrostriatal cell loss in patients with Parkinson's disease or clinically uncertain parkinsonism: a systematic review" 3032:

The incidence rate of falls in Parkinson's patients is approximately 45 to 68%, thrice that of healthy individuals, and half of such falls result in serious secondary injuries. Falls increase

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Fabbri M, Rascol O, Foltynie T, Carroll C, Postuma RB, Porcher R, et al. (2024). "Advantages and Challenges of Platform Trials for Disease Modifying Therapies in Parkinson's Disease".

2288:. However, several factors have been found to be associated with a decreased risk. The identification and mechanistic analysis of these factors may guide the development of new therapies. 1230:

factors. Nonetheless, the most significant risk factor is age with a prevalence of 1 percent in those aged over 65 and approximately 4.3 percent in age over 85. Genetic components comprise

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pain as the disease progresses. As of 2024, it remains unclear whether rigidity is caused by a distinct biomechanical process or if it is the manifestation of another cardinal sign of PD.

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is strongly associated with a decreased risk, reducing the chance of developing PD by 40–60%. Various tobacco and smoke components have been hypothesized to be neuroprotective, including

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Chendo I, Silva C, Duarte GS, Prada L, Voon V, Ferreira JJ (21 January 2022). "Frequency and Characteristics of Psychosis in Parkinson's Disease: A Systematic Review and Meta-Analysis".

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COMT metabolizes levodopa to 3-O-methyldopa. COMT inhibitors help stop this reaction, allowing for more levodopa to cross the blood–brain barrier and become dopamine where it is needed.

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Levodopa is available in oral, inhalation, and infusion form; inhaled levodopa can be used when oral levodopa therapy has reached a point where "off" periods have increased in length.

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Ceravolo R, Frosini D, Rossi C, Bonuccelli U (December 2009). "Impulse control disorders in Parkinson's disease: definition, epidemiology, risk factors, neurobiology and management".

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infections can trigger autoimmune reactions to alpha-synuclein, perhaps through molecular mimicry of viral proteins. Alpha-synuclein, and its aggregate form, Lewy bodies, can bind to

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Zhu J, Cui Y, Zhang J, Yan R, Su D, Zhao D, et al. (2024). "Temporal trends in the prevalence of Parkinson's disease from 1980 to 2023: a systematic review and meta-analysis".

3452:, which has distributed more than $ 115 million for research and nearly $ 50 million for education and advocacy programs since its founding in 1957 by William Black; the 2155:

or MSA usually has early onset of autonomic dysfunction (such as orthostasis), and may have autonomic predominance, cerebellar symptom predominance, or Parkinsonian predominance.

2049:(CT) scans of people with PD usually appear normal. Magnetic resonance imaging has become more accurate in diagnosis of the disease over time, specifically through iron-sensitive 12944: 8094:

Mahlknecht P, Krismer F, Poewe W, Seppi K (April 2017). "Meta-analysis of dorsolateral nigral hyperintensity on magnetic resonance imaging as a marker for Parkinson's disease".

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therapy for the motor symptoms of PD with the aim of delaying the initiation of levodopa therapy, thus delaying the onset of levodopa's complications. Dopamine agonists include

12960:"Safety and Tolerability of Multiple Ascending Doses of PRX002/RG7935, an Anti-α-Synuclein Monoclonal Antibody, in Patients With Parkinson Disease: A Randomized Clinical Trial" 7944:

Rizzo G, Copetti M, Arcuti S, Martino D, Fontana A, Logroscino G (February 2016). "Accuracy of clinical diagnosis of Parkinson disease: A systematic review and meta-analysis".

3606:(drugs that target the causes or damage) are approved for Parkinson's, so this is a major focus of Parkinson's research. Active research directions include the search for new 15634:

Chua WY, Wang JD, Chan CK, Chan L, Tan E (September 2024). "Risk of aspiration pneumonia and hospital mortality in Parkinson disease: A systematic review and meta-analysis".

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Wallace ER, Segerstrom SC, van Horne CG, Schmitt FA, Koehl LM (2022). "Meta-Analysis of Cognition in Parkinson's Disease Mild Cognitive Impairment and Dementia Progression".

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Only 5–10% of levodopa crosses the blood–brain barrier. Much of the remainder is metabolized to dopamine elsewhere in the body, causing a variety of side-effects, including

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of dopamine, levodopa, can pass through to the brain where it is readily converted to dopamine. Administration of levodopa temporarily diminishes the motor symptoms of PD.

805:(cycles per second). PD tremor tends to occur in the hands, but can affect other parts of the body, such as legs, arms, tongue, or lips, as well. It is often described as " 17373: 17368: 870:. This latter may occur prior to other typical symptoms, but the exact neurobiological mechanism, and therefore possible connections with other symptoms, remains unknown. 535:

can support the diagnosis. Usual onset is in people over 60 years of age, of whom about one percent are affected. In those younger than 50, it is termed "early-onset PD".

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Hasnain M, Vieweg WV, Baron MS, Beatty-Brooks M, Fernandez A, Pandurangi AK (July 2009). "Pharmacological management of psychosis in elderly patients with parkinsonism".

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Despite ongoing research efforts, Parkinson's disease has no known cure. Patients are typically managed by a holistic approach that combines lifestyle modifications with

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care. Palliative-care team members can help answer questions and guide people with PD on these complex and emotional topics to help them make decisions based on values.

11015:"Are there differences in the prevalence of palliative care-related problems in people living with advanced cancer and eight non-cancer conditions? A systematic review" 8037:"The 'swallow tail' appearance of the healthy nigrosome - a new accurate test of Parkinson's disease: a case-control and retrospective cross-sectional MRI study at 3T" 6392:

Bloem BR, Boonstra TA (December 2023). "The inadequacy of current pesticide regulations for protecting brain health: the case of glyphosate and Parkinson's disease".

3112:, and life expectancy. Although PD incidence and prevalence may vary by race and ethnicity, significant disparities in care, diagnosis, and study participation limit 2474:

dopa pumps may be useful. Late-stage Parkinson's disease presents challenges requiring a variety of treatments, including those for psychiatric symptoms particularly

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is difficult due to the disease's often decade-long prodromal period. Most noteworthy environmental factors include pesticide exposure and contact with heavy metals.

6678:"Double Trouble: Association of Malignant Melanoma with Sporadic and Genetic Forms of Parkinson's Disease and Asymptomatic Carriers of Related Genes: A Brief Report" 1047:

is characterized by emotional indifference and arises in about 46 percent of cases. Diagnosis is difficult, as it may become indistinct from symptoms of depression.

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and non-motor systems of the body. The symptoms usually emerge slowly, and, as the disease progresses, non-motor symptoms become more common. Usual symptoms include

17935: 16536: 15490:

Fereshtehnejad SM, Zeighami Y, Dagher A, Postuma RB (July 2017). "Clinical criteria for subtyping Parkinson's disease: biomarkers and longitudinal progression".

12455: 3302:) of a disease with symptoms of tremor, stiffness, staring, and stooped posture. In 2009, a systematic description of PD was found in the Hungarian medical text 2143:

Secondary parkinsonism – The multiple causes of parkinsonism can be differentiated through careful history, physical examination, and appropriate imaging. Other

2023: 13269:

Bhattacharyya KB (2017). "Chapter One - Hallmarks of Clinical Aspects of Parkinson's Disease Through Centuries". In Bhatia KP, Chaudhuri KR, Stamelou M (eds.).

12544: 3509:

showed signs of PD when he was 38, but was undiagnosed until he was 42, and has been called the "world's most famous Parkinson's patient". Whether he had PD or

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common with older age at onset. Thus, dopamine agonists are the preferred initial treatment for younger-onset PD, and levodopa is preferred for older-onset PD.

620:

The loss of dopamine-producing neurons in the substantia nigra initially presents as movement abnormalities, leading to Parkinson's further categorization as a

2683:

Apomorphine, a dopamine agonist, may be used to reduce off periods and dyskinesia in late PD. It is administered only by intermittent injections or continuous

10539:"The Impact of Mind-body Exercises on Motor Function, Depressive Symptoms, and Quality of Life in Parkinson's Disease: A Systematic Review and Meta-analysis" 14630:"Alcohol Use Disorder, Neurodegeneration, Alzheimer's and Parkinson's Disease: Interplay Between Oxidative Stress, Neuroimmune Response and Excitotoxicity" 3465: 2237:– levodopa resistance, cognitive predominance before motor symptoms, and fluctuating cognitive symptoms, (visual hallucinations are common in this disease) 12126: 7430:

Tan EK, Chao YX, West A, Chan LL, Poewe W, Jankovic J (June 2020). "Parkinson disease and the immune system - associations, mechanisms and therapeutics".

4827:

França M, Parada Lima J, Oliveira A, Rosas MJ, Vicente SG, Sousa C (September 2023). "Visuospatial memory profile of patients with Parkinson's disease".

3420:

need for interventions to reduce PD incidence, delay disease progression, and alleviate symptom burden that may reduce the future economic burden of PD.

2435:. The patient's age at disease onset as well as the stage of the disease often help determine which of the aforementioned drug groups is most effective. 2057:

sequences at a magnetic field strength of at least 3T, both of which can demonstrate absence of the characteristic 'swallow tail' imaging pattern in the

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neurons that modulate the previously described pathways. Consequently, dopaminergic dysfunction in these systems can disrupt their respective components—

1114:

Cognitive disturbances can occur in early stages or before diagnosis, and increase in prevalence and severity with duration of the disease. Ranging from

13189: 12195: 6121:

Khani M, Cerquera-Cleves C, Kekenadze M, Wild Crea P, Singleton AB, Bandres-Ciga S (May 2024). "Towards a Global View of Parkinson's Disease Genetics".

1193:. Seborrheic dermatitis is recognized as a premotor feature that indicates dysautonomia and demonstrates that PD can be detected not only by changes of 7244:

Obeso JA, Rodriguez-Oroz MC, Goetz CG, Marin C, Kordower JH, Rodriguez M, et al. (June 2010). "Missing pieces in the Parkinson's disease puzzle".

6264:

Lashuel HA (July 2020). "Do Lewy bodies contain alpha-synuclein fibrils? and Does it matter? A brief history and critical analysis of recent reports".

4299:"Age at Onset Influences Progression of Motor and Non-Motor Symptoms during the Early Stage of Parkinson's Disease: A Monocentric Retrospective Study" 3072:

was estimated to be 1.51 per 1000. Although it is around 40% more common in men, age is the dominant predeterminant of Parkinson's. Consequently, as

16732: 14075:

Hansen D, Ling H, Lashley T, Holton JL, Warner TT (April 2019). "Review: Clinical, neuropathological and genetic features of Lewy body dementias".

12421: 3979:"Global Trends in the Incidence, Prevalence, and Years Lived With Disability of Parkinson's Disease in 204 Countries/Territories From 1990 to 2019" 2808:

Four areas of the brain have been treated with neural stimulators in PD. These are the globus pallidus interna, thalamus, subthalamic nucleus, and

2005:. They assess motor symptoms (bradykinesia, rest tremors, etc.) using clinical diagnostic criteria. The finding of Lewy bodies in the midbrain on 12292: 5794: 3691: 3068:

As of 2024, Parkinson's is the second most common neurodegenerative disease and the fastest-growing in total number of cases. As of 2023, global

815:

is often considered the most important feature of Parkinson's disease and is also present in atypical parkinsonism. It describes difficulties in

16727: 16036: 16265: 12261: 11930: 2412: 2173:

Vascular parkinsonism is the phenomenon of the presence of Parkinson's disease symptoms combined with findings of vascular events (such as a

1861:, may in fact be the toxic forms of the protein. In people with dementia, a generalized presence of Lewy bodies is common in cortical areas. 352: 791:

Four motor symptoms are considered as cardinal signs in PD: tremor, bradykinesia, rigidity, and postural instability, collectively known as

16529: 1880:

activity. Iron accumulation in the substantia nigra is typically observed in conjunction with the protein inclusions. It may be related to

692: 15342:"The synaptic pathology of alpha-synuclein aggregation in dementia with Lewy bodies, Parkinson's disease and Parkinson's disease dementia" 7336:"Subsequent risks of Parkinson disease in patients with autoimmune and related disorders: a nationwide epidemiological study from Sweden" 2944: 1589: 291: 14983:

Varden R, Walker R, O'Callaghan A (2024). "No trend to rising rates: A review of Parkinson's prevalence studies in the United Kingdom".

5222:

Macías-García P, Rashid-López R, Cruz-Gómez ÁJ, Lozano-Soto E, Sanmartino F, Espinosa-Rosso R, et al. (9 May 2022). Aasly J (ed.).

18407: 18363: 17466: 12936: 6022:"Association of Coffee Consumption and Prediagnostic Caffeine Metabolites With Incident Parkinson Disease in a Population-Based Cohort" 2113: 1692:

circuits (each named for its primary projection area)—leading to symptoms related to movement, attention, and learning in the disease.

777:

among others. In general, motor symptoms such as postural instability and gait abnormalities tend to appear as the disease progresses.

16045: 15181:

Bereczki D (2010). "The description of all four cardinal signs of Parkinson's disease in a Hungarian medical text published in 1690".

18744: 17355: 14412:"Alpha-synuclein in Parkinson's disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction" 1893: 1506: 13226:

Torres-Pasillas G, Chi-Castañeda D, Carrillo-Castilla P, Marín G, Hernández-Aguilar ME, Aranda-Abreu GE, et al. (5 June 2023).

3341:, and others. Anticholinergics and surgery were the only treatments until the use of levodopa, which, although first synthesized by 18222: 17839: 17652: 14570:

Singh A, Tripathi P, Singh S (2021). "Neuroinflammatory responses in Parkinson's disease: relevance of Ibuprofen in therapeutics".

10397: 10201: 10064: 9120: 8915: 7737: 2038:

accuracy is 73.8%. Overall, 80.6% of PD diagnoses are accurate, and 82.7% of diagnoses using the Brain Bank criteria are accurate.

801:

is the most common presenting sign and may appear at rest as well as during intentional movement with a frequency between 4–6

6578:"Spatial lipidomics reveals brain region-specific changes of sulfatides in an experimental MPTP Parkinson's disease primate model" 3489:

In the 21st century, the diagnosis of Parkinson's among notable figures has increased the public's understanding of the disorder.

2151:

involves motor symptoms with early onset of cognitive dysfunction and hallucinations which precede motor symptoms. Alternatively,

17632: 17345: 16522: 12095: 9946:"Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients" 2871:(OT) aims to promote health and quality of life by helping people with the disease to participate in a large percentage of their 2326:

is also strongly associated with neuroprotection. In laboratory models, caffeine has been shown to be neuroprotective due to its

7383:"Herpes zoster correlates with increased risk of Parkinson's disease in older people: A population-based cohort study in Taiwan" 1588:

Three major pathways connect the basal ganglia to other brain areas: direct, indirect, and hyperdirect pathway, all part of the

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is suggested as another significant mechanism in disease progression. It is characterized by cell death through high levels of

12322: 3084:

This increase may be due to a number of global factors, including prolonged life expectancy, increased industrialisation, and

17350: 16982: 16480: 14833:

Ben-Shlomo Y, Darweesh S, Llibre-Guerra J, Marras C, Luciano MS, Tanner C (2024). "The epidemiology of Parkinson's disease".

13679: 13654: 13635: 13616: 13597: 13560: 13513: 13466: 13435: 13414: 13395: 13368: 13341: 13314: 13287: 13161: 10911: 10409: 10213: 10058: 9247: 9114: 8927: 8859: 7731: 5593: 4069: 667:. Neurodegenerative diseases that feature parkinsonism but have distinct features are grouped under the separate umbrella of 12519: 4704: 18754: 17188: 17176: 16638: 11986: 9559: 6162:"Identification of 27 allele-specific regulatory variants in Parkinson's disease using a massively parallel reporter assay" 2821: 2394: 2358: 1982: 15080:

Lees AJ (2007). "Unresolved issues relating to the shaking palsy on the celebration of James Parkinson's 250th birthday".

13334:

Ferri's differential diagnosis: a practical guide to the differential diagnosis of symptoms, signs, and clinical disorders

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causes one in five cases, implying an association with the onset of PD. Risk is increased by co-exposure to, for example,

18419: 17567: 16262: 15917: 13645:

Tolosa E, Katzenschlager R (2007). "Pharmacological management of Parkinson's disease". In Tolosa E, Jankovic JJ (eds.).

6304:"DNA repair and neurological disease: From molecular understanding to the development of diagnostics and model organisms" 1959:

by the liver, another protein commonly found in people with PD, that can lead to an increase in peripheral inflammation.

1788: 10434:"The effectiveness of exercise interventions for people with Parkinson's disease: a systematic review and meta-analysis" 8330: 3851: 2147:

can have similar movement symptoms but have a variety of associated symptoms. Some of these are also synucleinopathies.

2050: 18734: 18729: 17669: 17644: 17479: 17407: 17340: 16895: 16029: 11886: 10653:

Barichella M, Cereda E, Pezzoli G (October 2009). "Major nutritional issues in the management of Parkinson's disease".

7701: 3870: 3545: 2280:

As of 2024, no disease-modifying therapies exist that reverse or slow neurodegeneration, processes respectively termed

13447:"Chapter 8: Considerations for Patient and Target Selection in Deep Brain Stimulation surgery for Parkinson's disease" 12447: 4501: 2259:– levodopa resistance, restrictive vertical gaze, specific MRI findings, and early and different postural difficulties 18455: 18275: 18173: 17110: 16913: 12552: 3449: 3133: 2463: 2066: 2062: 17: 15659:

Won JH, Byun SJ, Oh B, Park SJ, Seo HG (September 2007). "Cognitive dysfunction and dementia in Parkinson disease".

1285:

As of 2024, around 90 genetic risk variants across 78 genomic loci have been identified. Notable risk genes include

18547: 17784: 17755: 17696: 16497: 11904: 8281: 2031: 1970:

and colon problems years before motor issues arise. Alpha-synuclein is produced in the gut and may migrate via the

1920: 1351: 1206: 1041:

which is more prevalent in PD. Nonetheless, suicidal attempts themselves are lower than in the general population.

476:, but a few contributing factors have been identified. Pathophysiology is characterized by progressively expanding 57:

Parkinson disease, idiopathic or primary parkinsonism, hypokinetic rigid syndrome, paralysis agitans, shaking palsy

31: 18724: 13987:"Behavioural interventions for swallowing in subjects with Parkinson's disease: A mixed methods systematic review" 7589:"Review for "Parkinson's disease and intensive exercise therapy — An updated systematic review and meta-analysis"" 4922:"Behavioural interventions for swallowing in subjects with Parkinson's disease: A mixed methods systematic review" 1821:

One mechanism causing brain cell death results from abnormal accumulation of the protein alpha-synuclein bound to

1222:

As of 2024, the underlying cause of PD is unknown, yet is assumed to be influenced primarily by an interaction of

17789: 17584: 17509: 17229: 10938:

Ghoche R (December 2012). "The conceptual framework of palliative care applied to advanced Parkinson's disease".

3219: 3183:

published the first comprehensive medical description of the disease as a neurological syndrome in his monograph

3104:

to be just 30%. The influence of multiple genetic and environmental factors complicates epidemiological efforts.

2054: 1119: 1099: 1037:, memory problems, or altered appetite, share similarities with psychiatric signs caused by PD. It may result in 625: 442: 205: 35: 14340:"Association of Parkinson's disease to Parkinson's plus syndromes, Lewy body dementia, and Alzheimer's dementia" 14309:

Bologna M, Truong D, Jankovic J (2022). "The etiopathogenetic and pathophysiological spectrum of parkinsonism".

12708:

Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, et al. (March 2017). "Parkinson disease".

12118: 12038: 10852:"The national agenda for quality palliative care: the National Consensus Project and the National Quality Forum" 4582: 3088:. Although genetics is the sole factor in a minority of cases, most cases of Parkinson's are likely a result of 1094:(ICD) can be seen in approximately 19 percent of all patients and, in the context of PD, are grouped along with 984:

within the first three minutes after raising to an upright position that can be seen in 30–50 percent of cases.

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Defined as the onset of development of recurrent falls, wheelchair dependence, dementia, or facility placement.

3754: 3731: 2741: 2680:

increased sexual activity, eating, gambling, and shopping) more strongly than other antiparkinson medications.

2592: 2256: 2202: 2163: 279: 15521:"The elephant in the room: critical reflections on mortality rates among individuals with Parkinson's disease" 13700:"A multiple treatment comparison meta-analysis of monoamine oxidase type B inhibitors for Parkinson's disease" 4402: 2923:

for liquid intake and an upright posture when eating may be useful; both measures reduce the risk of choking.

18739: 17968: 17686: 17662: 17423: 17308: 17224: 17166: 16936: 16715: 16452: 16295: 16090: 16022: 14496:

Ascherio A, Schwarzschild MA (2016). "The epidemiology of Parkinson's disease: risk factors and prevention".

13297:

Dissanayaka NN (8 March 2021). "Chapter 9: Anxiety in Parkinson's Disease". In Byrne GJ, Panchana NA (eds.).

12016: 11960: 5454:"Screening, Diagnosis, and Management of Parkinson's Disease Psychosis: Recommendations From an Expert Panel" 3502: 3445: 3089: 2905: 2860: 15109:

Louis ED (1997). "The shaking palsy, the first forty-five years: a journey through the British literature".

13741:

Caballol N, Martí MJ, Tolosa E (September 2007). "Cognitive dysfunction and dementia in Parkinson disease".

12576:"Robin Williams had dementia with Lewy bodies – so, what is it and why has it been eclipsed by Alzheimer's?" 9897:"Different Generations of Type-B Monoamine Oxidase Inhibitors in Parkinson's Disease: From Bench to Bedside" 6729:"Association between gout and the development of Parkinson's disease: a systematic review and meta-analysis" 5503:"Impulse control disorders associated with dopaminergic drugs: A disproportionality analysis using vigibase" 2193:

Parkinson-plus syndrome – Multiple diseases can be considered part of the Parkinson's plus group, including

18631: 18168: 17701: 17546: 17392: 16766: 16231: 14455:"Depletion of dopamine in Parkinson's disease and relevant therapeutic options: A review of the literature" 10113: 3660: 3288: 3215: 3170: 2915:

Muscles and nerves that control the digestive process may be affected by PD, resulting in constipation and

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and difficulty to control impulsive urges and are positively correlated with the use of dopamine agonists.

1058: 1033:

and is more prevalent in women. The diagnosis can be challenging since some symptoms of depression such as

933: 466: 299: 13552: 13505: 13458: 7618:"Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson's Disease" 5747:"A review of the gastrointestinal, olfactory, and skin abnormalities in patients with Parkinson's disease" 5544:"Cognitive Impairment in Parkinson's Disease: Epidemiology, Clinical Profile, Protective and Risk Factors" 3169:, credited as the first to comprehensively describe it. Patient Pierre D. (right) served as the model for 2756:

was approved for the management of PD psychosis. Doxepin and rasagline may reduce physical fatigue in PD.

765:

Non-motor symptoms may precede the onset of motor symptoms by up to 20 years. These include constipation,

17876: 17674: 16902: 16203: 13541:"Chapter 3: Pathological mechanisms and clinical aspects of GBA1 mutation-associated Parkinson's disease" 10894:

Lorenzl S, Nübling G, Perrar KM, Voltz R (2013). "Palliative treatment of chronic neurologic disorders".

6160:

Farrow SL, Gokuladhas S, Schierding W, Pudjihartono M, Perry JK, Cooper AA, et al. (February 2024).

3727: 3603: 3595: 3586: 3262: 2451: 2432: 2311: 2018: 1347: 1154: 1102:(DDS) within the broader spectrum of impulsive and compulsive behaviors (ICB). They are characterized by 774: 659:. These four symptoms are not exclusive to Parkinson's and can occur in many other conditions, including 550:. As the disease progresses, these medications become less effective and produce a side effect marked by 18689: 12413: 7102:"Oxidative Stress and Neuroinflammation in Parkinson's Disease: The Role of Dopamine Oxidation Products" 3116:

and lead to conflicting results. Within the United States, high rates of PD have been identified in the

823:

involved in bradykinesia lead to the characteristic reduced facial expression known as "masked face" or

18626: 17541: 17380: 16930: 16602: 12284: 9689:"Stalevo 150 mg/37.5 mg/200 mg Film-coated Tablets – Summary of Product Characteristics (SmPC) – (emc)" 6727:

Fazlollahi A, Zahmatyar M, Alizadeh H, Noori M, Jafari N, Nejadghaderi SA, et al. (October 2022).

3345:

in 1911, did not enter clinical use until 1967. By the late 1980s deep brain stimulation introduced by

1359: 1158: 867: 586: 10233:

Bronstein JM, Tagliati M, Alterman RL, Lozano AM, Volkmann J, Stefani A, et al. (February 2011).

5224:"Neuropsychiatric Symptoms in Clinically Defined Parkinson's Disease: An Updated Review of Literature" 4653:

Becker D, Maric A, Schreiner SJ, Büchele F, Baumann CR, Waldvogel D (2 December 2022). Ahmed S (ed.).

3448:, which has provided more than $ 180 million in care, research, and support services since 1982, 1955:. In addition, high levels of pro-inflammatory cytokines, such as IL-6, can lead to the production of 1479:

is also strongly implicated as a risk factor. Additionally, although the underlying cause is unknown,

18636: 18605: 17983: 17866: 17452: 17330: 17298: 17272: 17250: 17099: 16678: 8183:"Neuroimaging Detectable Differences between Parkinson's Disease Motor Subtypes: A Systematic Review" 6885:"Basal ganglia for beginners: the basic concepts you need to know and their role in movement control" 3533: 2234: 2206: 1928: 1275: 1115: 1022: 629: 578: 410: 275: 12388: 9136:"Cognitive training interventions for dementia and mild cognitive impairment in Parkinson's disease" 5403:"Emerging role of psychosis in Parkinson's disease: From clinical relevance to molecular mechanisms" 4780:"Peripheral neuropathy in Parkinson's disease: prevalence and functional impact on gait and balance" 18684: 18600: 18595: 18292: 18255: 18247: 18065: 18034: 17775: 17760: 17397: 17171: 16585: 16305: 16100: 15931: 13540: 13493: 12253: 10114:"FDA approves first drug to treat hallucinations and delusions associated with Parkinson's disease" 7029:

Chen R, Gu X, Wang X (April 2022). "α-Synuclein in Parkinson's disease and advances in detection".

3518: 3330: 3117: 2897: 2809: 2366: 2002: 1709: 1643: 1628: 1620: 1091: 925: 751: 668: 524: 14381:

Olfatia N, Shoeibia A, Litvanb I (2019). "Progress in the treatment of Parkinson-Plus syndromes".

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Connolly BS, Lang AE (30 April 2014). "Pharmacological treatment of Parkinson disease: a review".

5661:

Dodet P, Houot M, Leu-Semenescu S, Corvol JC, Lehéricy S, Mangone G, et al. (February 2024).

4655:"Onset of Postural Instability in Parkinson's Disease Depends on Age rather than Disease Duration" 3672: 1250:. Timing of exposure factor may influence the progression or severity of certain stages. However, 988:

can impair the perfusion of organs situated above the heart, particularly the brain, resulting in

133: 18621: 18128: 17978: 17973: 17930: 17747: 17402: 17335: 17091: 16909: 16761: 16751: 16595: 16485: 14866:

Deliz JR, Tanner CM, Gonzalez-Latapi P (2024). "Epidemiology of Parkinson's Disease: An Update".

12958:

Jankovic J, Goodman I, Safirstein B, Marmon TK, Schenk DB, Koller M, et al. (October 2018).

7768:

Armstrong MJ, Okun MS (February 2020). "Diagnosis and Treatment of Parkinson Disease: A Review".

7157: 4963:"Gastrointestinal involvement in Parkinson's disease: pathophysiology, diagnosis, and management" 3656: 3652: 3006: 2837: 2564: 2479: 2246: 2198: 2152: 2144: 1948: 1768: 1705: 1624: 1062: 1034: 969: 943: 937: 572: 295: 196: 16514: 15690:"Risk and mortality of aspiration pneumonia in Parkinson's disease: a nationwide database study" 12656:

McFarthing K, Rafaloff G, Baptista M, Mursaleen L, Fuest R, Wyse RK, et al. (24 May 2022).

11210:"Risk and mortality of aspiration pneumonia in Parkinson's disease: a nationwide database study" 9212: 7535:"Altered Gut Microbiota Related to Inflammatory Responses in Patients With Huntington's Disease" 2070: 554:. Diet and certain forms of rehabilitation have shown some effectiveness at improving symptoms. 18499: 18138: 18029: 17963: 17871: 17267: 17259: 17214: 16890: 16862: 15311:

Fahn S (2008). "The history of dopamine and levodopa in the treatment of Parkinson's disease".

9240:

Levodopa pharmacokinetics – from stomach to brain: A study on patients with Parkinson's disease

6676:

Koros C, Simitsi AM, Bougea A, Papagiannakis N, Antonelou R, Pachi I, et al. (July 2023).

5166:"Apathy and Anxiety in De Novo Parkinson's Disease Predict the Severity of Motor Complications" 4728:"Diagnostic value of micrographia in Parkinson's disease: a study with [I]FP-CIT SPECT" 4604:

Asci F, Falletti M, Zampogna A, Patera M, Hallett M, Rothwell J, et al. (September 2023).

3777: 3648: 3498: 3321:

in 1938. The underlying changes in dopamine signaling were identified in the 1950s, largely by

3202:

There was little discussion or investigation of the "shaking palsy" until 1861, when Frenchman

3121: 3093: 3041: 2778: 2471: 2459: 2347: 2331: 1862: 1476: 1150: 912:

is known to be present in up to 55 percent of PD patients. While it is responsible for most of

903: 879: 755: 664: 582: 555: 414: 332: 270: 15971: 13667: 7895:

Mustafa HI, Fessel JP, Barwise J, Shannon JR, Raj SR, Diedrich A, et al. (January 2012).

6883:

Rocha GS, Freire MA, Britto AM, Paiva KM, Oliveira RF, Fonseca IA, et al. (August 2023).

6345:"Towards a methodological uniformization of environmental risk studies in Parkinson's disease" 4606:"Rigidity in Parkinson's disease: evidence from biomechanical and neurophysiological measures" 4473: 4045: 3880: 3701: 3152: 1525: 992:. This can eventually lead to fainting and is associated with higher morbidity and mortality. 18694: 18427: 18307: 18214: 18193: 17282: 17156: 16974: 16952: 16867: 16790: 16700: 16687: 16612: 16070: 15877: 15605:

Murueta-Goyena A, Muiño O, Gómez-Esteban JC (March 2017). "Dementia in Parkinson's disease".

14716:

Grotewolda N, Albina RL (2024). "Update: Protective and risk factors for Parkinson disease".

13228:"Olfactory Dysfunction in Parkinson's Disease, Its Functional and Neuroanatomical Correlates" 13140:

Jenner P (2014). "An overview of adenosine A2A receptor antagonists in Parkinson's disease".

5936: 5788: 4726:

Eklund M, Nuuttila S, Joutsa J, Jaakkola E, Mäkinen E, Honkanen EA, et al. (July 2022).

3314: 2568: 2213: 2194: 2178: 2167: 1787:, and especially mitochondria. Mitochondrial damage triggers neuroinflammatory responses via 1569: 1182: 1123: 909: 895: 852: 446: 201: 15039:"The history of Parkinson's disease: early clinical descriptions and neurological therapies" 13607:

Dickson DV (2007). "Neuropathology of movement disorders". In Tolosa E, Jankovic JJ (eds.).

10978:

Wilcox SK (January 2010). "Extending palliative care to patients with Parkinson's disease".

10235:"Deep brain stimulation for Parkinson disease: an expert consensus and review of key issues" 9944:

Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, et al. (September 2004).

8957:"Revisiting the Medical Management of Parkinson's Disease: Levodopa versus Dopamine Agonist" 8474:"Therapeutic Interventions for Vascular Parkinsonism: A Systematic Review and Meta-analysis" 7475:"Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes" 6302:

Abugable AA, Morris JL, Palminha NM, Zaksauskaite R, Ray S, El-Khamisy SF (September 2019).

4297:

De Carolis L, Galli S, Bianchini E, Rinaldi D, Raju M, Caliò B, et al. (January 2023).

4239: 2619:

Three COMT inhibitors are used to treat adults with PD and end-of-dose motor fluctuations –

916:

and pain in PD, its role in postural instability and motor impairment is poorly understood.

538:

No cure is known; treatment aims to mitigate symptoms. Initial treatment typically includes

18519: 18432: 18188: 18008: 17609: 17589: 17219: 17036: 16925: 16291: 16277: 16110: 16082: 13425: 11734: 8850:

Olanow CW, Stocchi F, Lang AE (2011). "The non-motor and non-dopaminergic features of PD".

8048: 7486: 6576:

Kaya I, Nilsson A, Luptáková D, He Y, Vallianatou T, Bjärterot P, et al. (July 2023).

4778:

Corrà MF, Vila-Chã N, Sardoeira A, Hansen C, Sousa AP, Reis I, et al. (January 2023).

4536: 3764:

arising from excess dopamine release by the transplanted tissues, have also been observed.

3626: 3510: 3223: 3045: 2868: 2769: 2483: 2105: 1689: 1665: 1374: 1322: 1227: 996: 963: 844: 747: 644: 434: 209: 163: 15239:

Coffey RJ (2009). "Deep brain stimulation devices: a brief technical history and review".

14024: 14019: 3317:

reported that the substantia nigra was the main brain structure affected, corroborated by

2135:

can help locate denervation of the muscles of the heart which can support a PD diagnosis.

8: 18749: 18569: 18551: 18514: 18504: 18358: 18260: 18237: 18085: 18077: 17856: 17834: 17562: 17148: 16795: 16650: 16590: 16200: 16145: 15906: 14675:"Calcium channel blockers and Parkinson's disease: a systematic review and meta-analysis" 14410:

Calabresi P, Mechelli A, Natale G, Volpicelli-Daley L, Di Lazzaro G, Ghiglieri V (2023).

9334:

Aquino CC, Fox SH (January 2015). "Clinical spectrum of levodopa-induced complications".

8429:

Gupta D, Kuruvilla A (December 2011). "Vascular parkinsonism: what makes it different?".

7811:

Poewe W, Wenning G (November 2002). "The differential diagnosis of Parkinson's disease".

7616:

Kim S, Kwon SH, Kam TI, Panicker N, Karuppagounder SS, Lee S, et al. (August 2019).

6026: 5012:"Gastrointestinal Dysfunction in Parkinson's Disease: Current and Potential Therapeutics" 3739: 3411:

The costs of PD to society are high; in 2007, the largest share of direct cost came from

3334: 3203: 3162: 2872: 2790: 2712: 2339: 2327: 2148: 1810: 1717: 1647: 1573: 1516: 1489: 1314: 1095: 454: 303: 15757: 15732: 15588: 15563: 15545: 15520: 15294: 15269: 15210:

Blonder LX (2018). "Historical and cross-cultural perspectives on Parkinson's disease".

14771: 14746: 14699: 14674: 14479: 14454: 14364: 14339: 14032:

Islam MS, Azim F, Saju H, Zargaran A, Shirzad M, Kamal M, et al. (September 2021).

14023: This article incorporates text from this source, which is available under the 13626:

Fung VS, Thompson PD (2007). "Rigidity and spasticity". In Tolosa E, Jankovic E (eds.).

13445:

Dallapiazza RF, De Vloo PD, Fomenko A, Lee DJ, Hamani C, Munhoz RP, et al. (2018).

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Dixon L, Duncan D, Johnson P, Kirkby L, O'Connell H, Taylor H, et al. (July 2007).

10415: 10395: 10219: 10199: 10046: 10044: 9664:"Comtess 200 mg film-coated Tablets – Summary of Product Characteristics (SmPC) – (emc)" 9102: 9100: 8933: 8913: 8052: 7719: 7717: 7490: 7128: 7101: 6994: 6969: 6911: 6884: 6855: 6828: 6704: 6677: 6602: 6577: 6553: 6528: 6527:

Dorsey ER, Zafar M, Lettenberger SE, Pawlik ME, Kinel D, Frissen M, et al. (2023).

6504: 6479: 6455: 6428: 6369: 6344: 6186: 6161: 6050: 6021: 5771: 5746: 5687: 5662: 4630: 4605: 4540: 4260: 3569:

Please help update this article to reflect recent events or newly available information.

3532:, the American actor and comedian, had been diagnosed with PD, but his autopsy revealed 3505:, which he founded in 2000, has raised over $ 2 billion for Parkinson's research. Boxer 3394:

Please help update this article to reflect recent events or newly available information.

2567:

so it cannot be taken as a medicine to boost the brain's depleted levels of dopamine. A

2532:

Please help update this article to reflect recent events or newly available information.

2446:

between symptom control and medication side effects. For example, the administration of

671:

or, alternatively, atypical parkinsonian disorders. Parkinson's disease can result from

18232: 17829: 17681: 17318: 17303: 17291: 17041: 16992: 16829: 16692: 16580: 16287: 16086: 15802: 15714: 15689: 15438: 15413: 15366: 15341: 15164: 15139: 15063: 15038: 14966: 14939: 14921: 14896: 14816: 14789: 14656: 14629: 14553: 14527:"Chasing Protection in Parkinson's Disease: Does Exercise Reduce Risk and Progression?" 14526: 14436: 14411: 14292: 14265: 14247: 14222: 14204: 14179: 14161: 14134: 14058: 14033: 13968: 13943: 13925: 13900: 13847: 13822: 13804: 13779: 13766: 13724: 13699: 13574: 13527: 13480: 13320: 13190:"FDA approves new add-on drug to treat off episodes in adults with Parkinson's disease" 13153: 13093: 13068: 12984: 12959: 12918: 12874: 12826: 12801: 12782: 12733: 12682: 12657: 12633: 12606: 12369: 12357: 12234: 11846: 11821: 11695: 11668: 11234: 11209: 10903: 10850:

Ferrell B, Connor SR, Cordes A, Dahlin CM, Fine PG, Hutton N, et al. (June 2007).

10827: 10802: 10783: 10734: 10707: 10688: 10565: 10538: 10519: 10473: 10364: 10339: 10261: 10234: 10170: 10143: 10019: 9994: 9921: 9896: 9813: 9756: 9739: 9614: 9490: 9465: 9446: 9403: 9359: 9299: 9272: 9160: 9135: 9078: 9051: 9029: 8981: 8956: 8832: 8572: 8570: 8568: 8549: 8524: 8500: 8473: 8454: 8406: 8379: 8258: 8231: 8207: 8182: 8163: 8119: 8071: 8036: 7969: 7921: 7896: 7872: 7847: 7793: 7642: 7617: 7561: 7534: 7507: 7474: 7455: 7407: 7382: 7363: 7269: 6804: 6779: 6755: 6728: 6653: 6626: 6241: 6210: 6002: 5989: 5964: 5912: 5887: 5638: 5621: 5570: 5543: 5478: 5453: 5429: 5402: 5343: 5318: 5250: 5223: 5190: 5165: 5138: 5113: 5089: 5062: 5038: 5011: 4987: 4962: 4897: 4872: 4804: 4779: 4752: 4727: 4681: 4654: 4559: 4524: 4450: 4425: 4379: 4352: 4325: 4298: 4005: 3978: 3773: 3761: 3346: 3109: 2932: 2867:

disorders associated with PD. Speech therapy and specifically LSVT may improve speech.

2720: 2382: 2229: 1963: 1956: 1899: 1677: 1661:

to subthalamic nucleus, modulating basal ganglia activity with rapid excitatory input.

1298: 1186: 1000: 985: 676: 633: 520: 242: 142: 15429: 14846: 14509: 14338:

Prajjwal P, Kolanu ND, Reddy YB, Ahmed A, Marsool MD, Santoshi K, et al. (2024).

13959: 13916: 13360: 12906: 11117: 11031: 11014: 10868: 10851: 9970: 9945: 9912: 9844: 9801: 9481: 8972: 8346: 7848:"The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease" 7312: 7153:"Editor's evaluation: Lipid hydroperoxides promote sarcopenia through carbonyl stress" 6405: 5864: 4033: 3456:, founded in 1961; and the European Parkinson's Disease Association, founded in 1992. 3313:

described microscopic particles in affected brains, later named Lewy bodies. In 1919,

1869:, characteristic of Alzheimer's disease, are uncommon unless the person has dementia. 1088:. It might overlap with other psychiatric symptoms, making the diagnosis challenging. 18478: 18003: 17993: 17925: 17851: 17735: 17081: 17047: 17019: 17010: 16942: 16918: 16785: 16633: 16121: 15942: 15762: 15719: 15676: 15647: 15622: 15593: 15550: 15507: 15478: 15443: 15400: 15396: 15371: 15328: 15299: 15256: 15252: 15227: 15198: 15194: 15169: 15126: 15097: 15068: 15025: 15021: 14996: 14992: 14971: 14926: 14883: 14854: 14821: 14776: 14733: 14729: 14704: 14661: 14616: 14587: 14558: 14513: 14484: 14441: 14398: 14394: 14369: 14326: 14297: 14252: 14209: 14166: 14121: 14092: 14063: 14008: 13973: 13930: 13887: 13852: 13809: 13758: 13729: 13675: 13650: 13631: 13612: 13593: 13566: 13556: 13519: 13509: 13472: 13462: 13431: 13410: 13391: 13374: 13364: 13337: 13310: 13283: 13167: 13157: 13098: 12989: 12922: 12910: 12878: 12866: 12862: 12831: 12786: 12774: 12725: 12687: 12638: 12500: 12361: 12238: 12230: 12191: 11851: 11802: 11798: 11762: 11723:"Exploring public perceptions and awareness of Parkinson's disease: A scoping review" 11700: 11357: 11313: 11286: 11250: 11239: 11063: 11036: 10995: 10955: 10951: 10917: 10907: 10873: 10832: 10787: 10775: 10739: 10708:"Systematic review on strength training in Parkinson's disease: an unsolved question" 10680: 10570: 10511: 10465: 10405: 10369: 10320: 10266: 10209: 10175: 10095: 10054: 10024: 9975: 9926: 9848: 9805: 9761: 9688: 9645: 9606: 9541: 9495: 9450: 9438: 9407: 9395: 9351: 9304: 9253: 9243: 9165: 9110: 9083: 9033: 9021: 8986: 8923: 8865: 8855: 8836: 8824: 8554: 8505: 8446: 8442: 8411: 8360: 8263: 8212: 8167: 8155: 8111: 8076: 8017: 7973: 7961: 7926: 7877: 7828: 7797: 7785: 7727: 7693: 7647: 7601: 7588: 7566: 7512: 7459: 7447: 7412: 7355: 7316: 7261: 7208: 7133: 7082: 7046: 6999: 6943: 6916: 6860: 6809: 6760: 6709: 6658: 6607: 6558: 6509: 6480:"Metal Exposure and Risk of Parkinson Disease: A Systematic Review and Meta-Analysis" 6460: 6409: 6374: 6325: 6281: 6246: 6191: 6142: 6055: 6006: 5994: 5917: 5868: 5817: 5776: 5727: 5723: 5692: 5643: 5575: 5524: 5483: 5434: 5383: 5348: 5299: 5255: 5195: 5143: 5094: 5043: 4992: 4943: 4902: 4873:"Treatment of autonomic dysfunction in Parkinson disease and other synucleinopathies" 4850: 4809: 4757: 4686: 4635: 4564: 4455: 4384: 4330: 4279: 4010: 3959: 3918: 3907:"Differential diagnosis of Parkinson's disease and other neurodegenerative disorders" 3735: 3326: 3284: 3026: 2848: 2828: 2711:) increase the amount of dopamine in the basal ganglia by inhibiting the activity of 2523: 2475: 2343: 1838: 1834: 1796: 1748: 1461: 1438: 1038: 887: 856: 759: 721: 621: 257: 178: 122: 17444: 15982: 15911: 15847:

Neurology-related videos, including several showing people with Parkinson's disease.

14628:

Kamal H, Tan GC, Ibrahim SF, Shaikh MF, Mohamed IN, Mohamed RM, et al. (2020).

13578: 13531: 13484: 13324: 13278:

Cooper G, Eichhorn G, Rodnitzky RL (2008). "Parkinson's disease". In Conn PM (ed.).

13067:

Schweitzer JS, Song B, Herrington TM, Park TY, Lee N, Ko S, et al. (May 2020).

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Miguel-Puga A, Villafuerte G, Salas-Pacheco J, Arias-Carrión O (22 September 2017).

8458: 7367: 5710:

Niemann N, Billnitzer A, Jankovic J (January 2021). "Parkinson's disease and skin".

5519: 5502: 5452:

Pahwa R, Isaacson SH, Small GW, Torres-Yaghi Y, Pagan F, Sabbagh M (December 2022).

2385:—possibly due to alcohol's urate-increasing effect—alcohol abuse may increase risk. 68: 18348: 18302: 18270: 18118: 18096: 18061: 17824: 17706: 17657: 17604: 17579: 17574: 17531: 17519: 17204: 17075: 17070: 16855: 16850: 16343: 16124: 15782: 15752: 15744: 15709: 15701: 15668: 15639: 15614: 15583: 15575: 15540: 15532: 15499: 15468: 15433: 15425: 15392: 15361: 15353: 15320: 15289: 15281: 15248: 15219: 15190: 15159: 15151: 15118: 15089: 15058: 15050: 15017: 14988: 14961: 14951: 14916: 14908: 14875: 14850: 14842: 14811: 14801: 14766: 14758: 14725: 14694: 14686: 14651: 14641: 14608: 14579: 14548: 14538: 14505: 14474: 14466: 14431: 14423: 14390: 14359: 14351: 14318: 14287: 14277: 14242: 14234: 14199: 14191: 14156: 14146: 14135:"Molecular and Cellular Interactions in Pathogenesis of Sporadic Parkinson Disease" 14113: 14084: 14053: 14049: 14045: 13998: 13963: 13955: 13920: 13912: 13877: 13842: 13834: 13799: 13791: 13770: 13750: 13719: 13711: 13548: 13501: 13454: 13356: 13302: 13239: 13149: 13088: 13080: 12979: 12971: 12902: 12858: 12821: 12813: 12764: 12717: 12677: 12669: 12628: 12618: 12490: 12353: 12318: 12226: 12187: 11841: 11833: 11794: 11752: 11742: 11690: 11680: 11229: 11221: 11026: 10987: 10947: 10899: 10863: 10822: 10818: 10814: 10767: 10729: 10719: 10670: 10662: 10560: 10550: 10503: 10478: 10455: 10445: 10359: 10351: 10316: 10312: 10308: 10256: 10246: 10165: 10160: 10155: 10087: 10014: 10006: 9965: 9957: 9916: 9908: 9840: 9797: 9751: 9618: 9598: 9531: 9485: 9477: 9430: 9421:

Paik J (June 2020). "Levodopa Inhalation Powder: A Review in Parkinson's Disease".

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Raj T, Rothamel K, Mostafavi S, Ye C, Lee MN, Replogle JM, et al. (May 2014).

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Connie T, Aderinola TB, Ong TS, Goh MKO, Erfianto B, Purnama B (12 December 2022).

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Dommershuijsen LJ, Darweesh SK, Ben-Shlomo Y, Kluger BM, Bloem BR (October 2023).

14266:"Infectious Etiologies of Parkinsonism: Pathomechanisms and Clinical Implications" 13225: 10991: 9714:"Ongentys 50 mg hard capsules – Summary of Product Characteristics (SmPC) – (emc)" 4836: 4525:"Quantitative Measurement of Rigidity in Parkinson´s Disease: A Systematic Review" 2798: 2369:(CCB) may also have a protective effect, with a 22% risk decrease found in a 2024 18524: 18482: 18353: 18340: 18287: 18282: 18265: 18145: 17940: 17912: 17713: 17536: 17475: 17126: 16817: 16413: 16388: 16368: 16358: 16320: 15936: 14470: 12975: 12495: 12478: 12091: 11747: 10355: 10091: 9536: 9519: 9134:

Orgeta V, McDonald KR, Poliakoff E, Hindle JV, Clare L, Leroi I (February 2020).

8061: 7957: 7912: 7824: 7633: 6320: 6303: 6106: 6089: 6040: 5848: 5762: 5294: 5277: 3619: 3591: 3280: 3275: 3180: 3166: 3085: 3073: 3056: 3018: 2786: 2684: 2487: 2307: 2299: 2285: 1998: 1990: 1616: 1608: 1454: 1328: 1259: 1231: 989: 951: 899: 610: 606: 543: 528: 513: 501: 450: 390: 360: 263: 18574: 15985: 15054: 12658:"Parkinson's Disease Drug Therapies in the Clinical Trial Pipeline: 2022 Update" 12344:

Jones JM (December 2004). "Great shakes: famous people with Parkinson disease".

11990: 11822:"Current and projected future economic burden of Parkinson's disease in the U.S" 11820:

Yang W, Hamilton JL, Kopil C, Beck JC, Tanner CM, Albin RL, et al. (2020).

11165: 10251: 9961: 9713: 9663: 9567: 8471: 7398: 4057: 3329:. In 1997, alpha-synuclein was found to be the main component of Lewy bodies by 2768:

Placement of an electrode into the brain: the head is stabilised in a frame for

2249:– levodopa resistance, rapidly progressive, autonomic failure, stridor, present 1919:. Microglia can proliferate and be over-activated by alpha-synuclein binding to 18509: 18450: 18374: 18183: 18150: 18133: 18123: 17183: 17132: 16960: 16669: 16546: 16491: 16460: 16234: 15705: 15579: 15536: 14879: 14583: 14427: 14195: 14117: 12817: 12607:"The Disease Modification Conundrum in Parkinson's Disease: Failures and Hopes" 11861: 11721:

Crooks S, Carter G, Wilson CB, Wynne L, Stark P, Doumas M, et al. (2023).

11400: 11225: 11141: 11129: 9434: 9391: 8230:

Suwijn SR, van Boheemen CJ, de Haan RJ, Tissingh G, Booij J, de Bie RM (2015).

8151: 7078: 6985: 6935: 6901: 6845: 6745: 6643: 6593: 6360: 6177: 5809: 5678: 5469: 5334: 5129: 4978: 4743: 3801: 3784: 3529: 3493: 3474: 3412: 3338: 3322: 3292: 3258: 3254: 3241: 3108:

these geographic differences include genetic variation, environmental factors,

3037: 2864: 2424: 2411:(L-dopa) is the most effective for motor symptoms and is often combined with a 2250: 2083: 1967: 1912: 1866: 1830: 1596: 1194: 1138: 1054: 973: 820: 816: 624:. In 30% of cases, disease progression leads to the cognitive decline known as 516:

and environmental mechanisms, medications, lifestyle, and previous conditions.

348: 186: 16002: 15947: 15896: 15618: 15357: 14956: 14806: 14690: 14322: 13882: 13865: 13446: 13306: 13109: 13048: 12623: 11837: 11388: 10010: 9602: 8540: 8396: 8248: 8012: 7995: 7551: 7443: 7042: 6277: 5888:"Unraveling Parkinson's Disease Neurodegeneration: Does Aging Hold the Clues?" 5221: 4275: 3995: 1025:

is the most common NPS and occurs in nearly half of all patients. It features

958:(prevalence up to 82 percent). Complications resulting from dysphagia include 702: 18718: 18543: 18494: 17812: 17209: 17161: 17031: 16800: 16756: 16607: 16135: 16014: 15990: 15748: 14790:"Caffeine and Parkinson's Disease: Multiple Benefits and Emerging Mechanisms" 14646: 14543: 14282: 14180:"Viruses, parkinsonism and Parkinson's disease: the past, present and future" 13069:"Personalized iPSC-Derived Dopamine Progenitor Cells for Parkinson's Disease" 13012: 12060: 11347: 11345: 10898:. Handbook of Clinical Neurology. Vol. 118. Elsevier. pp. 133–139. 10507: 9257: 8869: 8686: 8490: 8181:

Boonstra JT, Michielse S, Temel Y, Hoogland G, Jahanshahi A (February 2021).

7688: 6694: 4522: 4315: 3522: 3514: 3310: 3188: 3187:. He presented six clinical cases, including three he had observed afar near 2916: 2641: 2438: 2370: 2094: 2087: 2074: 1986: 1908: 1877: 1721: 1685: 1577: 1557: 1553: 1174: 1073: 947: 770: 660: 497: 493: 287: 250: 15892: 14003: 13986: 13244: 13227: 12150:"Michael J. Fox talks funding breakthrough research for Parkinson's disease" 11908: 11890: 11552: 11054:

Casey G (August 2013). "Parkinson's disease: a long and difficult journey".

10340:"Does vigorous exercise have a neuroprotective effect in Parkinson disease?" 10282: 10280: 7781: 7671: 7498: 7167: 7152: 5419: 4938: 4921: 4795: 4621: 2805:

involves surgical destruction of the globus pallidus to control dyskinesia.

1825:

in damaged cells. This insoluble protein accumulates inside neurons forming

1141:

are common in PD and affect about two thirds of all patients. They comprise

711: 80: 18397: 18178: 17730: 16705: 16575: 16558: 16398: 16383: 16328: 16301: 16058: 16049: 15766: 15723: 15680: 15651: 15626: 15597: 15554: 15511: 15503: 15482: 15447: 15375: 15332: 15303: 15285: 15260: 15231: 15223: 15202: 15173: 15101: 15072: 15029: 15000: 14975: 14930: 14887: 14858: 14825: 14780: 14737: 14708: 14665: 14620: 14591: 14562: 14517: 14488: 14445: 14402: 14373: 14330: 14301: 14256: 14213: 14170: 14125: 14096: 14067: 14012: 13977: 13934: 13891: 13856: 13813: 13762: 13733: 13570: 13523: 13476: 13378: 13171: 13102: 12993: 12914: 12870: 12835: 12778: 12729: 12691: 12642: 12504: 12365: 11855: 11806: 11785:

Findley LJ (September 2007). "The economic impact of Parkinson's disease".

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Elbers RG, Verhoef J, van Wegen EE, Berendse HW, Kwakkel G (October 2015).

10099: 10028: 9979: 9930: 9852: 9809: 9765: 9649: 9633: 9610: 9560:"Tasmar 100 mg Tablets – Summary of Product Characteristics (SmPC) – (emc)" 9545: 9499: 9442: 9399: 9355: 9315: 9308: 9169: 9087: 9025: 8990: 8828: 8820: 8737: 8558: 8509: 8450: 8415: 8364: 8267: 8216: 8159: 8115: 8080: 8021: 7965: 7930: 7832: 7789: 7697: 7651: 7570: 7516: 7451: 7416: 7359: 7320: 7265: 7212: 7137: 7118: 7086: 7050: 7003: 6947: 6920: 6864: 6813: 6764: 6713: 6662: 6611: 6562: 6513: 6464: 6445: 6413: 6378: 6329: 6285: 6250: 6195: 6146: 6059: 5998: 5921: 5872: 5821: 5780: 5731: 5696: 5647: 5579: 5528: 5487: 5438: 5387: 5352: 5303: 5259: 5240: 5199: 5147: 5098: 5047: 4996: 4947: 4906: 4854: 4813: 4761: 4690: 4671: 4639: 4568: 4459: 4441: 4388: 4353:"Tremor in Parkinson's Disease: From Pathophysiology to Advanced Therapies" 4334: 4283: 4100: 4014: 3963: 3922: 3906: 3750: 3611: 3607: 3506: 3478: 3342: 3318: 3101: 2893: 2753: 2527: 2189:

Hot Cross Bun sign that is commonly found in MRI of multiple system atrophy

2132: 2079: 2058: 1966:, an area of the body highly implicated in PD. People with PD have altered 1952: 1947:

to T cells. CD4+ T cells, activated by this process, are able to cross the

1944: 1924: 1884:, protein aggregation, and neuronal death, but the mechanisms are obscure. 1858: 1792: 1760: 1729: 1725: 1673: 1658: 1636: 1484: 1422: 1247: 1127: 1016: 929: 860: 812: 806: 792: 786: 739: 731: 679:, in which there is no clearly identifiable cause. The latter, also called 656: 640: 568: 438: 426: 418: 174: 167: 155: 15564:"Prognostic factors for falls in Parkinson's disease: a systematic review" 15404: 15130: 15122: 14940:"Parkinson's disease in China: a forty-year growing track of bedside work" 14151: 13838: 13780:"Repairing the Brain: Cell Replacement Using Stem Cell-Based Technologies" 13084: 11342: 11301: 10771: 10581: 8922:(Technical report). London: Royal College of Physicians. pp. 59–100. 8609: 7881: 7863: 6495: 6429:"Mercury and Parkinson's Disease: Promising Leads, but Research Is Needed" 6231: 5501:

De Wit LE, Wilting I, Souverein PC, van der Pol P, Egberts TC (May 2022).

5164:

Hinkle JT, Perepezko K, Gonzalez LL, Mills KA, Pontone GM (January 2021).

4523:

Ferreira-Sánchez MD, Moreno-Verdú M, Cano-de-la-Cuerda R (February 2020).

3977:

Ou Z, Pan J, Tang S, Duan D, Yu D, Nong H, et al. (7 December 2021).

3048:. Aspiration pneumonia is responsible for 70% of deaths in those with PD. 2407:

levels or by directly mimicking dopamine's effect on the patient's brain.

1898:

The neuroimmune interaction is heavily implicated in PD pathology. PD and

18382: 18113: 17844: 17594: 16664: 16625: 16567: 16446: 16418: 16403: 16393: 16273: 16175: 16165: 16140: 16096: 15997: 15966: 15831: 15473: 15457:"Prognosis in chronic progressive neurologic disease: a narrative review" 15456: 13024: 13000: 12721: 11262: 10432:

Goodwin VA, Richards SH, Taylor RS, Taylor AH, Campbell JL (April 2008).

10277: 9589:

Scott LJ (September 2016). "Opicapone: A Review in Parkinson's Disease".

9520:"Neurological and psychiatric management using COMT inhibitors: A review" 9466:"Levodopa in Parkinson's Disease: Current Status and Future Developments" 8766: 8764: 8597: 7203: 7186: 6627:"Biological links between traumatic brain injury and Parkinson's disease" 4184: 3651:-family growth factor), and enzymes such as glutamic acid decarboxylase ( 3196: 2924: 2901: 2802: 2665: 2661: 2649: 2583: 2467: 2420: 2378: 2159: 2061:

substantia nigra. In a meta-analysis, absence of this pattern was highly

1971: 1940: 1806: 1756: 1733: 1669: 1282:, although harboring one of these mutations may not lead to the disease. 1262:

features, hence lowering the risk of PD. About 85 percent of cases occur

1211: 1103: 959: 913: 891: 614: 505: 232: 15270:"Frederic Lewy: how the two World Wars changed his life, work, and name" 14264:

Limphaibool N, Iwanowski P, Holstad MJ, Kobylarek D, Kozubski W (2019).

14178:

Leta V, Urso D, Batzu L, Lau YH, Mathew D, Boura I, et al. (2022).

13207: 11105: 10724: 9871: 9859: 8355: 7587:

Gamborg M, Hvid LG, Dalgas U, Langeskov-Christensen M (3 October 2021).

5079: 5028: 4845: 4424:

Bologna M, Paparella G, Fasano A, Hallett M, Berardelli A (March 2020).

18699: 18392: 18297: 17998: 17723: 17718: 17514: 16775: 16645: 16438: 16434: 16408: 16363: 16353: 16338: 16242: 16221: 16216: 16211: 16190: 16185: 16180: 16106: 14912: 14409: 14238: 13795: 12753:"Update of the MDS research criteria for prodromal Parkinson's disease" 12751:

Heinzel S, Berg D, Gasser T, Chen H, Yao C, Postuma RB (October 2019).

12673: 10460: 9068: 8198: 7335: 6795: 6544: 5980: 5963:

De Miranda BR, Goldman SM, Miller GW, Greenamyre JT, Dorsey ER (2022).

5903: 5663:"Sleep disorders in Parkinson's disease, an early and multiple problem" 5560: 5379: 5181: 4160: 4039: 4021: 3622:

agents. To aid in earlier diagnosis, research criteria for identifying

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