No cure for PD is known, and treatment focuses on alleviating symptoms. Initial treatment typically includeslevodopa,MAO-B inhibitors, ordopamine agonists. As the disease progresses, these medications become less effective and may causeinvoluntary muscle movements. Diet and rehabilitation therapies can help improve symptoms.Deep brain stimulation is used to manage severe motor symptoms when drugs are ineffective. Little evidence exists for treatments addressing non-motor symptoms, such as sleep disturbances and mood instability. Life expectancy for those with PD is near-normal, but is decreased for early-onset.
The cardinal motor features are tremor, bradykinesia, rigidity, and postural instability, collectively termedparkinsonism.[15] Appearing in 70–75% of those with PD,[15][16] tremor is often the predominant motor symptom.[15] Resting tremor is the most common, but kinetic tremors—occurring during voluntary movements—and postural tremor—preventing upright, stable posture—also occur.[16] Tremor largely affects the hands and feet:[16] a classic parkinsonian tremor is "pill-rolling", a resting tremor in which the thumb and index finger make contact in a circular motion at 4–6 Hz frequency.[17][18]
Bradykinesia describes difficulties inmotor planning, beginning, and executing, resulting in overall slowed movement with reduced amplitude that affects sequential and simultaneous tasks.[19] Bradykinesia can also lead tohypomimia, reduced facial expressions.[18]Rigidity, also called rigor, refers to a feeling of stiffness and resistance to passive stretching of muscles.[20]Postural instability typically appears in later stages, leading toimpaired balance andfalls.[21] Postural instability also leads to a forward stooping posture.[22]
Beyond the cardinal four, other motor deficits, termed secondary motor symptoms, commonly occur.[23] Notably, gait disturbances result in theparkinsonian gait, which includes shuffling andparoxysmal deficits, where a normal gait is interrupted by rapid footsteps—known as festination—or sudden stops, impairing balance and causing falls.[24][25] Most people with PD experience speech problems, includingstuttering,hypophonic, "soft" speech,slurring, and festinating speech (rapid and poorly intelligible).[26] Handwriting is commonly altered in PD, decreasing in size—known asmicrographia—and becoming jagged and sharply fluctuating.[27] Grip and dexterity are also impaired.[28]
Neuropsychiatric symptoms such asanxiety,apathy,depression,hallucination, andimpulse control disorders occur in up to 60% of those with PD.[29] They often precede motor symptoms, vary with disease progression,[29] and may appear at any stage of the disease including theprodromal phase.[30] Non-motor fluctuations, includingdysphoria,fatigue, and slowness of thought, are also common.[31] Some neuropsychiatric symptoms are not directly caused by neurodegeneration, but rather by its pharmacological management.[32]
Table featuring the prevalence of neuropsychiatric symptoms in PD
Neuropsychiatric symptom prevalence in Parkinson's disease[33]
Autonomic nervous system failures, known asdysautonomia, can appear at any stage of PD.[36][37] They are among the most debilitating symptoms and greatly reduce quality of life.[38] Although almost all individuals with PD have cardiovascular autonomic dysfunction, only some are symptomatic.[38] Chiefly,orthostatic hypotension—a sustainedblood pressure drop of at least 20 mmHgsystolic or 10 mmHgdiastolic after standing—occurs in 30–50% of cases. This can result inlightheadedness orfainting; subsequent falls are associated with higher morbidity and mortality.[38][39]
As of 2024, the cause of neurodegeneration in PD is unclear,[53] though it is believed to result from the interplay ofgenetic andenvironmental factors.[53] Most cases areidiopathic with no clearly identifiable cause, while about 5–10% are familial.[54] Around a third of familial cases can be attributed to a single monogenic cause.[54]
Molecularly, abnormal aggregation of alpha-synuclein is considered a key contributor to PDpathogenesis,[53] although the trigger for this aggregation is debated[55] and some forms of PD do not include these aggregations.[56] Also, the vulnerability of substantia nigra pars compacta (SNc) dopaminergic neurons to oxidative stress, caused in part by intracellular dopamine being toxic, has been proposed as a major contributor to the disease.[57]Proteostasis disruption and the dysfunction of cellorganelles, includingendosomes,lysosomes, andmitochondria, are implicated in pathogenesis.[53] Additionally, maladaptive immune and inflammatory responses are potential contributors.[53] The substantial heterogeneity in PD presentation and progression suggests the involvement of multiple interacting triggers and pathogenic pathways.[55]
Parkinson's can be narrowly defined as a genetic disease, as rare inherited gene variants have been firmly linked to monogenic PD, and most cases carry variants that increase PD risk.[53][58][59] PDheritability is estimated to range from 22 to 40%.[53] Around 15% of diagnosed individuals have afamily history, of which 5–10% can be attributed to a causative risk genemutation. Carrying one of these mutations may not lead to disease. Rates of familial PD vary by ethnicity; monogenic PD occurs in up to 40% ofArab-Berber and 20% ofAshkenazi Jewish people with PD.[59]
As of 2024, around 90 genetic risk variants across 78 genomic loci have been identified.[60] Notable risk variants includeSNCA (which encodes alpha-synuclein),LRRK2, andVPS35 forautosomal dominant inheritance, andPRKN,PINK1, andDJ1 forautosomal recessive inheritance.[53][61]LRRK2 is the most common autosomal dominant variant, responsible for 1–2% of all PD cases and 40% of familial cases.[62][54]Parkin variants are associated with nearly half of recessive, early-onset monogenic PD.[63] Mutations in theGBA1 gene, linked toGaucher's disease, can cause monogenic PD,[64] and are associated with cognitive decline.[62]
The limited heritability of Parkinson's strongly suggests environmental factors are involved, though identifying these risk factors and establishingcausality is challenging due to PD's decade-long prodromal period.[65]
Environmental toxicants such as air pollution and pesticides are strongly linked to PD.[66] Certain pesticides—such asparaquat,glyphosate, androtenone—are the most established environmental toxicants for PD and are likely causal.[67][68][69] PD prevalence is strongly associated with local pesticide use, and many pesticides are mitochondrial toxins.[70] Paraquat, for instance, structurally resembles metabolizedMPTP,[67] which selectively kills dopaminergic neurons by inhibitingmitochondrial complex 1 and is widely used tomodel PD.[71][67] Pesticide exposure after diagnosis may also accelerate disease progression.[67] Without high pesticide exposure, an estimated 20% of all PD cases would be prevented.[72]
Epidemiological evidence also supports the association of pesticide exposure with Parkinson's Disease. For example, a 2025 study found that people who lived within 1–3 miles of agolf course were at increased risk for developing Parkinson's Disease, and that people who obtained their drinking water from service areas containing a golf course had twice the risk of developing Parkinson's disease compared to controls.[73]
The hallmark of PD is the formation of protein aggregates, beginning with alpha-synuclein fibrils and followed by Lewy bodies and Lewy neurites.[74] Theprion hypothesis suggests that alpha-synuclein aggregates are pathogenic and can spread to neighboring, healthy neurons and seed new aggregates. Some propose that the heterogeneity of PD may stem from different "strains" of alpha-synuclein aggregates and varying anatomical sites of origin.[75][76] Alpha-synuclein propagation has been demonstrated in cell and animal models and is the most popular explanation for the progressive spread through specific neuronal systems.[77] However, therapeutic efforts to clear alpha-synuclein have failed.[78] Additionally, postmortem brain tissue analysis shows that alpha-synuclein pathology does not clearly progress through the nearest neural connections.[79]
In 2002,Heiko Braak and colleagues proposed that PD begins outside the brain and is triggered by a "neuroinvasion" of some unknown pathogen.[80][81] The pathogen enters through the nasal cavity and is swallowed into the digestive tract, initiating Lewy pathology in both areas.[69][80] This alpha-synuclein pathology may then travel from the gut to the central nervous system through thevagus nerve.[82] This theory could explain the presence of Lewy pathology in both the enteric nervous system and olfactory tract neurons, as well as clinical symptoms such as loss of smell and gastrointestinal problems.[81] Environmental toxicants ingested in a similar manner might also trigger PD.[83]
As 90% of PD cases are idiopathic, the identification of the risk factors that may influence disease progression or severity is critical.[84][65] The most significant risk factor in developing PD is age, with a prevalence of 1% in those over 65 and around 4.3% in those over 85.[85]Traumatic brain injury significantly increases PD risk, especially if recent.[86][87] Dairy consumption correlates with a higher risk, possibly due to contaminants such asheptachlor epoxide.[88] Although the connection is unclear,melanoma diagnosis is associated with a roughly 45% risk increase.[88] Also, an association was found betweenmethamphetamine use and PD risk.[88] Behavioral and psychological factors have also been associated with risk of Parkinson's disease. For example, a large study found that adults who reported being lonely had a greater risk of developing Parkinson's disease over a 15 years of follow-up.[89] Similarly, a meta-analysis found that neuroticism was associated with higher risk of incident Parkinson's disease.[90]
Although no compounds or activities have been mechanistically established asneuroprotective for PD,[91][92] several factors have been found to be associated with a decreased risk.[91]Tobacco use andsmoking are strongly associated with a decreased risk, reducing the chance of developing PD by up to 70%.[93][94][88] Various tobacco and smoke components have been hypothesized to be neuroprotective, includingnicotine,carbon monoxide, andmonoamine oxidase B inhibitors.[95][96] Consumption ofcaffeine as an ingredient ofcoffee ortea is also strongly associated with neuroprotection.[97]
Although findings have varied, usage ofnonsteroidal anti-inflammatory drugs (NSAIDs) such asibuprofen may be neuroprotective.[98][99]Calcium channel blockers may also have a protective effect, with a 22% risk reduction reported.[100] Higher blood concentrations ofurate—a potentantioxidant—have been proposed to be neuroprotective.[95][101] Although longitudinal studies observe a slight decrease in PD risk among those who consumealcohol—possibly due to alcohol's urate-increasing effect—alcohol abuse may increase risk.[102]
Parkinson's disease has two hallmark pathophysiological processes: the abnormal aggregation of alpha-synuclein that leads to Lewy pathology, and the degeneration of dopaminergic neurons in thesubstantia nigra pars compacta.[103][104] The death of these neurons reduces available dopamine in thestriatum, which in turn affects circuits controlling movement in thebasal ganglia.[104] By the time motor symptoms appear, 50–80% of all dopaminergic neurons in the substantia nigra have degenerated.[104]
Cell death and Lewy pathology, though, are not limited to the substantia nigra.[105] Thesix-stage Braak system holds that alpha-synuclein pathology begins in theolfactory bulb or outside the central nervous system in theenteric nervous system before ascending the brain stem.[106] In the third Braak stage, Lewy body pathology appears in the substantia nigra,[106] and by the sixth step, Lewy pathology has spread to the limbic and neocortical regions.[107] Although Braak staging offers a strong basis for PD progression, around 50% of individuals do not follow the predicted model.[108] Lewy pathology is highly variable and may be entirely absent in some persons with PD.[105][109]
Lewy bodies consist of a fibrillar exterior and a granular core. Although alpha-synuclein is the dominantproteinaceous component, the core contains mitochondrial and autophagosomal membrane components, suggesting a link with organelle dysfunction.[113][114] Whether Lewy bodies themselves contribute to or are simply the result of PD pathogenesis is unclear; alpha-synuclein oligomers can independently mediate cell damage, and neurodegeneration can precede Lewy body formation.[115]
Three major pathways—vesicular trafficking,lysosomal degradation, and mitochondrial maintenance—are known to be affected by and contribute to PD pathogenesis, with all three linked to alpha-synuclein.[116] High-risk gene variants also impair all three of these processes.[116] All steps of vesicular trafficking are impaired by alpha-synuclein. It blocksendoplasmic reticulum (ER) vesicles from reaching theGolgi—leading toER stress—and Golgi vesicles from reaching thelysosome, preventing alpha-synuclein degradation and leading to its build-up.[117] Risky gene variants, chieflyGBA, further compromise lysosomal function.[118] Although the mechanism is not well established, alpha-synuclein can impair mitochondrial function and cause subsequentoxidative stress. Mitochondrial dysfunction can, in turn, lead to further alpha-synuclein accumulation in apositive feedback loop.[119] Microglial activation, possibly caused by alpha-synuclein, is also strongly indicated.[120][121]
Mitochondrial dysfunction is well-established in PD.[122] Increasedoxidative stress and reducedcalcium buffering may contribute to neurodegeneration.[123] The finding thatMPP+—arespiratory complex I inhibitor and MPTP metabolite—caused parkinsonian symptoms strongly implied that mitochondria contributed to PD pathogenesis.[122] Additionally, faulty gene variants involved in familial PD—includingPINK1 andParkin—prevent the elimination of dysfunctional mitochondria throughmitophagy.[124]
Diagnosis of PD is largely clinical, relying onmedical history and examination of symptoms, with an emphasis on symptoms that appear in later stages.[127][128] Although early-stage diagnosis is not reliable,[128][129] prodromal diagnosis may consider previous family history of PD and possible early symptoms such asrapid eye movement sleep behavior disorder (RBD), reducedsense of smell, and gastrointestinal issues.[130] Isolated RBD is a particularly significant sign, as 90% of those affected will develop some form of neurodegenerative parkinsonism.[131] Diagnosis in later stages requires the manifestation of parkinsonism, specifically bradykinesia and rigidity or tremor. Further support includes other motor and non-motor symptoms and genetic profiling.[132]
A PD diagnosis is typically confirmed by any two of these criteria: responsiveness to levodopa, resting tremor, levodopa-induced dyskinesia, ordopamine transporter single-proton emission computed tomography confirmation.[132] If these criteria are not met, atypical parkinsonism is considered.[130] Definitive diagnoses can only be madepost mortem through pathological analysis.[128] Misdiagnosis is common, with a reported error rate near 25%, and diagnoses often change during follow-ups.[128][133] Diagnosis can be further complicated by multiple overlapping conditions.[128]
Unlike MRI, PET and SPECT useradioisotopes for imaging.[138] Both techniques can aid diagnosis by characterizing PD-associated alterations in the metabolism andtransport of dopamine in the basal ganglia.[139][140] Largely used outside the United States, iodine-123-meta-iodobenzylguanidinemyocardialscintigraphy can assess heart muscle denervation to support a PD diagnosis.[141]
The International Parkinson and Movement Disorder Society has proposed a set of criteria that, unlike the standard Queen's Square Brain Bank Criteria, includes non-exclusionary "red-flag" clinical features that may not suggest PD.[147] A large number of "red flags" has been proposed and adopted for various conditions that might mimic the symptoms of PD.[148] Diagnostic tests, including gene sequencing, molecular imaging techniques, and assessment of smell may also distinguish PD.[137] MRI is particularly powerful due to several unique features for atypical parkinsonisms.[137]
Levodopa resistance, rapidly progressive, autonomic failure, stridor, presentBabinski sign, cerebellar ataxia, and specific MRI findings like the "Hot Cross Bun"
Levodopa resistance, restrictive vertical gaze,pseudobulbar crying,eyelid twitching, specific MRI findings, and early and different postural difficulties
As of 2025, no disease-modifying therapies exist that reverse or slow neurodegeneration.[91][92] Management typically combines lifestyle modifications withphysical therapy.[151] Current pharmacological interventions purely target symptoms, by either increasing endogenousdopamine levels or directly mimicking dopamine's effect on the patient's brain.[152][151] These include dopamine agonists, MAO-B inhibitors, and levodopa—the most widely used and effective drug.[153][151] The optimal time to initiate pharmacological treatment is debated,[154] but initial dopamine agonist and MAO-B inhibitor treatment and later levodopa therapy are common.[155] Invasive procedures such asdeep brain stimulation may be used when medications are ineffective.[156][157]
Levodopa is the most widely used and most effective therapy—thegold standard—for PD treatment.[153] The compound occurs naturally and is the immediate precursor for dopamine synthesis in the dopaminergic neurons of the substantia nigra.[158] Levodopa administration reduces the dopamine deficiency in parkinsonism.[159][160]
Despite its efficacy, levodopa poses several challenges. Its administration has been called the "pharmacologist's nightmare".[161][162] Its metabolism outside the brain byaromatic L-amino acid decarboxylase andcatechol-O-methyltransferase can cause nausea and vomiting; inhibitors such ascarbidopa,entacapone, andbenserazide are usually taken with levodopa to mitigate these effects.[163][164][note 1] Long-term levodopa use may alsoinduce dyskinesia and motor fluctuations. Although this often causes levodopa use to be delayed to later stages, earlier administration leads to improved motor function and quality of life.[166]
Dopamine agonists are an alternative or complement to levodopa therapy. They activate dopamine receptors in the striatum, with reduced risk of motor fluctuations and dyskinesia, and are efficacious in both early- and late-stage PD.[167] The agonistapomorphine is often used for drug-resistant OFF time in later-stage PD.[167][168] After five years of use, impulse-control disorders may occur in over 40% of those taking dopamine agonists.[154] A problematic, narcotic-like withdrawal effect may occur when agonist use is reduced or stopped.[154][169] Compared to levodopa, dopamine agonists are more likely to cause fatigue, daytime sleepiness, and hallucinations.[169]
MAO-B inhibitors—such assafinamide,selegiline andrasagiline—increase the amount of dopamine in the basal ganglia by inhibiting the activity ofmonoamine oxidase B, an enzyme that breaks down dopamine.[170] These compounds mildly alleviate motor symptoms when used as monotherapy, but can also be used with levodopa and at any disease stage.[171] Common side effects are nausea, dizziness, insomnia, sleepiness, and orthostatic hypotension.[172] MAO-Bs are known to increase serotonin and cause a potentially dangerous condition known asserotonin syndrome.[173]
Treatments for non-motor symptoms of PD have not been well studied, and many medications are usedoff-label.[62] A diverse range of symptoms beyond those related to motor function can be treated pharmaceutically.[174] Examples includecholinesterase inhibitors for cognitive impairment andmodafinil forexcessive daytime sleepiness.[175]Fludrocortisone,midodrine, anddroxidopa are commonly used off-label for orthostatic hypotension related to autonomic dysfunction. Sublingualatropine orbotulinum toxin injections may be used off-label for drooling.SSRIs andSNRIs are often used for depression related to PD, but a risk exists ofserotonin syndrome with the SSRI or SNRI antidepressants.[62] Doxepin and rasagline may reduce physical fatigue in PD.[176]
DBS involves the implantation ofelectrodes calledneurostimulators, which send electrical impulses to specific parts of the brain.[156] DBS for thesubthalamic nucleus andglobus pallidus interna has high efficacy for up to 2 years, but long-term efficacy is unclear and likely decreases with time.[156] DBS typically targets rigidity and tremor,[182] and is recommended for PD patients who are intolerant or do not respond to medication.[157] Cognitive impairment is the most common exclusion criteria.[183]
Although pharmacological therapies can improve symptoms, autonomy, and the ability to perform everyday tasks is still reduced by PD. Rehabilitation is often useful, but the scientific support for any single rehabilitation treatment is limited.[184]
Exercise programs are often recommended, with preliminary evidence of efficacy.[185][186][187] Regularphysical exercise with or without physical therapy can be beneficial to maintain and improve mobility, flexibility, strength, gait speed, and quality of life.[185] Aerobic, mind-body, and resistance training may be beneficial in alleviating PD-associated depression and anxiety.[187][188]Strength training may increasemanual dexterity and strength, facilitating daily tasks that require grasping objects.[189] Aerobic exercise, resistance training, and balance- and task-specific training have been found to improve strength,VO2 Max and balance. While flexibility training is commonly used, it has a lower strength of recommendation compared to aerobic and resistance training.[190]
Exercise, like thetricycle ride of this PD patient, is often recommended.Participants at a Power for Parkinson's exercise class do exercises specifically targeting Parkinson's symptoms.
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 trunk, rhythmic initiation,diaphragmatic breathing, andmeditation.[191] Deep diaphragmatic breathing may also improve chest-wall mobility andvital capacity decreased by the stooped posture and respiratory dysfunctions of advanced Parkinson's.[192] Rehabilitation techniques targeting gait and the challenges posed by bradykinesia, shuffling, and decreased arm swing includepole walking,treadmill walking, andmarching exercises.[193] Long-term physiotherapy (greater than six months) reduces the need for antiparkinsonian medication; multidisciplinary rehabilitation programs combined with physiotherapy can result in reduction in the levodopa-equivalent dose.[194]
Speech therapies such as theLee Silverman voice treatment may reduce the effect of speech disorders associated with PD.[195]Occupational therapy as a rehabilitation strategy can improve quality of life by enabling people with PD to find engaging activities and communal roles, adapt to their living environment, and improve domestic and work abilities.[196]
PD poses digestive problems such as constipation andprolonged emptying of stomach contents, and a balanced diet with periodical nutritional assessments is recommended to avoid weight loss or gain and minimize the consequences of gastrointestinal dysfunction. In particular, a Mediterranean diet is advised and may slow disease progression.[197][198] As it can compete for uptake withamino acids derived from protein, levodopa should be taken 30 minutes before meals to minimize such competition. Low-protein diets may also be needed by later stages.[198] As the disease advances, swallowing difficulties often arise. Usingthickening agents for liquid intake and an upright posture when eating may be useful; both measures reduce the risk of choking.Gastrostomy can be used to deliver food directly into the stomach.[199][200] Increased water and fiber intakes are used to treat constipation.[201]
As PD is incurable, palliative care aims to improve the quality of life for both the patient and family by alleviating the symptoms and stress associated with illness.[202][203][204] Early integration of palliative care into the disease course is recommended, rather than delaying until later stages.[202] Palliative-care specialists can help with physical symptoms, emotional factors such as loss of function and jobs, depression, and fear, as well as existential concerns.[205] Palliative-care team members also help guide difficult decisions caused by disease progression, such as wishes for afeeding tube,noninvasive ventilator ortracheostomy, use ofcardiopulmonary resuscitation, and enteringhospice care.[206][207]
Severe cognitive or movement abnormalities[note 2]
Death
Mild-motor predominant
14.3
20.2
Intermediate
8.2
13.1
Diffuse malignant
3.5
8.1
As PD is aheterogeneous condition with multipleetiologies, prognostication can be difficult and prognoses can be highly variable.[208][210] On average, life expectancy is reduced in those with PD, with younger age of onset resulting in greater life expectancy decreases.[211] 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 after diagnosis were 20.2, 13.1, and 8.1.[208]
Around 30% of individuals with PD develop dementia, which is 12 times more likely to occur in the elderly with severe PD.[212] Dementia is less likely to arise in tremor-dominant PD.[213] Parkinson's disease dementia is associated with a reducedquality of life in people with PD and theircaregivers, increased mortality, and a higher probability of needingnursing home care.[214]
The incidence rate of falls is around 45 to 68%, three times that of healthy individuals, and half of such falls result in serious secondary injuries. Falls increasemorbidity andmortality.[215] Around 90% of those with PD develophypokinetic dysarthria, which worsens with disease progression and can hinder communication.[216] Over 80% develop dysphagia; consequent inhalation of gastric and oropharyngeal secretions can lead toaspiration pneumonia.[217]
As of 2024, PD is the second-most common neurodegenerative disease and the fastest growing in total cases.[218][219] As of 2023, globalprevalence was estimated to be 1.51 per 1000.[220] Although it is around 40% more common in men,[221] age is the dominant predeterminant of PD.[222] Consequently, asglobal life expectancy has increased, PD prevalence has also risen, with an estimated increase in cases by 74% from 1990 to 2016.[223] The number is predicted to rise to over 12 million by 2040.[224]
This increase may be due to a number of global factors, including prolonged life expectancy, increased industrialisation, anddecreased smoking.[223] Although genetics is the sole factor in a minority of cases, most cases of PD are likely a result ofgene-environment interactions;concordance studies withtwins have found PDheritability to be just 30%.[221] The influence of multiple genetic and environmental factors complicates epidemiological efforts.[225]
Relative to Europe and North America, disease prevalence is lower in Africa, but similar in Latin America.[226] Although China is predicted to have nearly half of the global PD population by 2030,[227] estimates of prevalence in Asia vary.[226] Potential explanations for these geographic differences include genetic variation, environmental factors,health care access, and life expectancy.[226] Although PD incidence and prevalence may vary by race and ethnicity, significant disparities in care, diagnosis, and study participation limitgeneralizability and lead to conflicting results.[226][225] Within the United States, high rates of PD have been identified in theMidwest, theSouth, and agricultural regions of other states, collectively termed the "PD belt".[228] The association between rural residence and PD has been hypothesized to be caused by environmental factors including herbicides, pesticides, and industrial waste.[228]
In 1877,Jean-Martin Charcot (left) named Parkinson's disease after the first person to comprehensively describe it,James Parkinson. Patient Pierre D. (right) served as the model forWilliam Gowers' illustration of the disease.[229]
In 1817, English physicianJames Parkinson published the first full medical description of the disease as a neurological syndrome in his monographAn Essay on the Shaking Palsy.[230][231] He presented six clinical cases, including three he had observed on the streets nearHoxton Square inLondon.[232] 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 thespinal cord.[233][234]
Little discussion of or investigation into the "shaking palsy" occurred until 1861, when FrenchmanJean-Martin Charcot—regarded as the father ofneurology—began expanding Parkinson's description, adding bradykinesia as one of the four cardinal symptoms.[233][232][234] In 1877, Charcot renamed the disease after Parkinson, as the tremor suggested by "shaking palsy" is not present in all.[232][234] Subsequent neurologists who made early advances to the understanding of PD includeArmand Trousseau,William Gowers,Samuel Kinnier Wilson, andWilhelm Erb.[235]
In 1912,Frederic Lewy described microscopic particles in affected brains, later named Lewy bodies.[240] In 1919,Konstantin Tretiakoff reported that the substantia nigra was the main brain structure affected, corroborated byRolf Hassler in 1938.[241] The underlying changes in dopamine signaling were identified in the 1950s, largely byArvid Carlsson andOleh Hornykiewicz.[242] In 1997,Polymeropoulos and colleagues at theNIH discovered the first gene for PD,[243]SNCA, which encodes alpha-synuclein. Alpha-synuclein was, in turn, found to be the main component of Lewy bodies bySpillantini,Trojanowski,Goedert, and others.[244] Anticholinergics and surgery were the only treatments until the use of levodopa,[245][246] which, although first synthesized byCasimir Funk in 1911,[247] did not enter clinical use until 1967.[248] By the late 1980s, deep brain stimulation introduced byAlim Louis Benabid and colleagues atGrenoble, France, emerged as an additional treatment.[249]
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.[250] As the condition progresses, tremor, other motor symptoms, difficulty communicating, or mobility issues may interfere with social engagement, causing individuals with PD to feel isolated.[251] 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.[252]
The economic cost of Parkinson's to both individuals and society is high.[253] In many low- and middle-income countries, public health systems may not fully cover Parkinson's disease therapies, leading to disparities in access to treatment. In contrast, high-income countries with universal healthcare typically cover standard treatments such as levodopa and specialist care.[253] Indirect costs include lifetime earnings losses due to premature death, productivity losses, and caregiver burdens.[254] The duration and progressive nature of PD can place a heavy burden on caregivers;[255] family members, such as spouses, dedicate around 22 hours per week to care.[254]
In 2010, the total economic burden of PD across Europe, including indirect and direct medical costs, was estimated to be €13.9 billion (US $14.9 billion).[256] The total burden in the United States was estimated to be $51.9 billion in 2017, and is projected to surpass $79 billion by 2037.[254] As of 2022, no rigorous economic surveys had been performed for low- or middle-income nations.[257] Preventive care has been identified as crucial to slow the rapidly increasing incidence of Parkinson's from overwhelming national health systems.[255]
The birthday of James Parkinson, 11 April, has been designated as World Parkinson's Day.[258] A red tulip was chosen by international organizations as the symbol of the disease in 2005; it represents the 'James Parkinson' tulipcultivar, registered in 1981 by a Dutch horticulturalist.[259]
Advocacy organizations include theNational Parkinson Foundation, which has provided more than $180 million in care, research, and support services since 1982,[260]Parkinson's Disease Foundation, 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;[261][262] theAmerican Parkinson Disease Association, founded in 1961;[263] and the European Parkinson's Disease Association, founded in 1992.[264]
ActorMichael J. Fox and boxerMuhammad Ali (center) are pictured in 2002 speaking before theUS Senate to urge increased funding for Parkinson's research.
In the 21st century, the diagnosis of PD among notable figures has increased the public's understanding of the disorder.[265] ActorMichael J. Fox was diagnosed with PD at 29 years old,[266] and has used his diagnosis to increase awareness of the disease.[267] To illustrate the effects of the disease, Fox has appeared without medication in television roles and before theUnited States Congress.[268]The Michael J. Fox Foundation, which he founded in 2000, has raised over $2 billion for Parkinson's research.[269]
MusicianOzzy Osbourne was diagnosed with PD; he performed a July 5, 2025, farewell reunion concert with the band he co-founded,Black Sabbath, weeks before his death. The event raised over $190 million, some of which went to Parkinson's disease research.[274]
Adolf Hitler is believed to have had PD, and the condition may have partially influenced his decision-making.[275][276][277]
As of 2024, no disease-modifying therapies exist that reverse or slow the progression of PD.[91][92] Active research directions include the search for newanimal models of the disease and development and trial ofgene therapy,stem cell transplants, andneuroprotective agents.[278] Improved treatments will likely combine therapeutic strategies to manage symptoms and enhance outcomes.[279] Reliablebiomarkers are needed for early diagnosis, and research criteria for their identification have been established.[280][281]
As thegut microbiome in PD is often disrupted and produces toxic compounds,fecal microbiota transplants might restore a healthy microbiome and alleviate various motor and non-motor symptoms.[282]Neurotrophic factors—peptides that enhance the growth, maturation, and survival of neurons—show modest results, but require invasive surgical administration.Viral vectors may represent a more feasible delivery platform.[286] Calcium channel blockers may restore the calcium imbalance present in PD, and are being investigated as a neuroprotective treatment.[287] Other therapies, such asdeferiprone, may reduce the abnormal accumulation of iron in PD.[287]
In contrast to other neurodegenerative disorders, many PD symptoms can be attributed to the loss of a single cell type. Consequently, dopaminergic neuron regeneration is a promising therapeutic approach.[288] Although most initial research sought to generate dopaminergic neuron precursor cells from fetal brain tissue,[289]pluripotent stem cells—particularlyinduced pluripotent stem cells (iPSC)—have become an increasingly popular tissue source.[290][291]
Both fetal and iPSC-derived DA neurons have been transplanted into patients in clinical trials.[292][293] Although some individuals have seen improvement, the results are highly variable. Adverse effects, such asdyskinesia arising from excess dopamine release by the transplanted tissues, have also been observed.[294][295]
Gene therapy for PD seeks to restore the healthy function of dopaminergic neurons in the substantia nigra by delivering genetic material—typically through a viral vector—to these diseased cells.[296][297] This material may deliver a functional,wild-type version of a gene, orknock down a pathological variant.[298] Experimental gene therapies for PD have aimed to increase the expression ofgrowth factors or enzymes involved in dopamine synthesis, such astyrosine hydroxylase.[299] The one-time delivery of genes circumvents the recurrent invasive administration required to administer some peptides and proteins to the brain.[300] MicroRNAs are an emerging PD gene therapy platform that may serve as an alternative to viral vectors.[301]
Bhattacharyya KB (2017). "Chapter One – Hallmarks of Clinical Aspects of Parkinson's Disease Through Centuries". In Bhatia KP, Chaudhuri KR, Stamelou M (eds.).Parkinson's Disease. International Review of Neurobiology. pp. 1–23.
Ferri FF (2010). "Chapter P".Ferri's differential diagnosis: a practical guide to the differential diagnosis of symptoms, signs, and clinical disorders (2nd ed.). Elsevier/Mosby.ISBN978-0-3230-7699-9.
Ascherio A, Schwarzschild MA (2016). "The epidemiology of Parkinson's disease: risk factors and prevention".Lancet Neurology.15 (12):1257–1272.doi:10.1016/S1474-4422(16)30230-7.PMID27751556.
Barichella M, Cereda E, Pezzoli G (October 2009). "Major nutritional issues in the management of Parkinson's disease".Movement Disorders.24 (13):1881–1892.doi:10.1002/mds.22705.hdl:2434/67795.PMID19691125.
Bereczki D (2010). "The description of all four cardinal signs of Parkinson's disease in a Hungarian medical text published in 1690".Parkinsonism & Related Disorders.16 (4):290–293.doi:10.1016/j.parkreldis.2009.11.006.PMID19948422.
Bologna M, Truong D, Jankovic J (2022). "The etiopathogenetic and pathophysiological spectrum of parkinsonism".Journal of the Neurological Sciences.433 120012:1–8.doi:10.1016/j.jns.2021.120012.PMID34642022.
Borghammer P (January 2018). "How does parkinson's disease begin? Perspectives on neuroanatomical pathways, prions, and histology".Movement Disorders.33 (1):48–57.doi:10.1002/mds.27138.PMID28843014.
Caballol N, Martí MJ, Tolosa E (September 2007). "Cognitive dysfunction and dementia in Parkinson disease".Mov. Disord.22 (Suppl 17): S358–66.doi:10.1002/mds.21677.PMID18175397.S2CID3229727.
Caproni S, Colosimo C (February 2020). "Diagnosis and Differential Diagnosis of Parkinson Disease".Clinical Geriatric Medicine.36 (1):13–24.doi:10.1016/j.cger.2019.09.014.PMID31733693.
Casey G (August 2013). "Parkinson's disease: a long and difficult journey".Nursing New Zealand.19 (7):20–24.PMID24195263.
Chen R, Gu X, Wang X (April 2022). "α-Synuclein in Parkinson's disease and advances in detection".Clinica Chimica Acta; International Journal of Clinical Chemistry.529:76–86.doi:10.1016/j.cca.2022.02.006.PMID35176268.
de Bie RM, Clarke CE, Espay AJ, Fox SH, Lang AE (March 2020). "Initiation of pharmacological therapy in Parkinson's disease: when, why, and how".Lancet Neurology.19 (5):452–461.doi:10.1016/S1474-4422(20)30036-3.PMID32171387.
Deliz JR, Tanner CM, Gonzalez-Latapi P (2024). "Epidemiology of Parkinson's Disease: An Update".Current Neurology and Neuroscience Reports.24 (6):163–179.doi:10.1007/s11910-024-01339-w.PMID38642225.
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".Movement Disorders.39 (9):1468–1477.doi:10.1002/mds.29899.PMID38925541.
Fahn S (2008). "The history of dopamine and levodopa in the treatment of Parkinson's disease".Movement Disorders.23 (S3):S497 –S508.doi:10.1002/mds.22028.PMID18781671.
Ghoche R (December 2012). "The conceptual framework of palliative care applied to advanced Parkinson's disease".Parkinsonism & Related Disorders.18 (Suppl 3):S2 –S5.doi:10.1016/j.parkreldis.2012.06.012.PMID22771241.
Gupta R, Kim C, Agarwal N, Lieber B, Monaco EA (2015). "Understanding the Influence of Parkinson Disease on Adolf Hitler's Decision-Making during World War II".World Neurosurgery.84 (5):1447–1452.doi:10.1016/j.wneu.2015.06.014.PMID26093359.
Hansen D, Ling H, Lashley T, Holton JL, Warner TT (April 2019). "Review: Clinical, neuropathological and genetic features of Lewy body dementias".Neuropathology and Applied Neurobiology.45 (7):635–654.doi:10.1111/nan.12554.PMID30977926.
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".Parkinsonism & Related Disorders.66:16–24.doi:10.1016/j.parkreldis.2019.07.018.PMID31324556.S2CID198132349.
Koh J, Ito H (January 2017). "Differential diagnosis of Parkinson's disease and other neurodegenerative disorders".Nihon Rinsho. Japanese Journal of Clinical Medicine.75 (1):56–62.PMID30566295.
Lees AJ (2007). "Unresolved issues relating to the shaking palsy on the celebration of James Parkinson's 250th birthday".Movement Disorders.22 (S17):S327 –S334.doi:10.1002/mds.21684.PMID18175393.
Leta V, Klingelhoefer L, Longardner K, Campagnolo M, Levent HÇ, Aureli F, et al. (May 2023). "Gastrointestinal barriers to levodopa transport and absorption in Parkinson's disease".European Journal of Neurology.30 (5):1465–1480.doi:10.1111/ene.15734.hdl:11577/3511466.PMID36757008.
Lozano CS, Tam J, Lozano AM (January 2018). "The changing landscape of surgery for Parkinson's Disease".Movement Disorders.33 (1):36–47.doi:10.1002/mds.27228.PMID29194808.
Louis ED (1997). "The shaking palsy, the first forty-five years: a journey through the British literature".Movement Disorders.12 (6):1068–1072.doi:10.1002/mds.870120638.PMID9399240.
McDonnell MN, Rischbieth B, Schammer TT, Seaforth C, Shaw AJ, Phillips AC (May 2018). "Lee Silverman Voice Treatment (LSVT)-BIG to improve motor function in people with Parkinson's disease: a systematic review and meta-analysis".Clinical Rehabilitation.32 (5):607–618.doi:10.1177/0269215517734385.PMID28980476.
Mirelman A, Bonato P, Camicioli R, Ellis TD, Giladi N, Hamilton JL, et al. (April 2019). "Gait impairments in Parkinson's disease".Lancet Neurology.17 (7):697–708.doi:10.1016/S1474-4422(19)30044-4.PMID30975519.
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".Movement Disorders.34 (9):1243–1251.doi:10.1002/mds.27779.PMID31291491.
Murueta-Goyena A, Muiño O, Gómez-Esteban JC (March 2017). "Dementia in Parkinson's disease".Journal of the Neurological Sciences.374:26–31.doi:10.1016/j.jns.2017.01.012.PMID28088312.
Olfatia N, Shoeibia A, Litvanb I (2019). "Progress in the treatment of Parkinson-Plus syndromes".Parkinsonism & Related Disorders.59:101–110.doi:10.1016/j.parkreldis.2018.10.006.PMID30314846.
Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, et al. (June 1997). "Mutation in the alpha-synuclein gene identified in families with Parkinson's disease".Science.276 (5321):2045–2047.doi:10.1126/science.276.5321.2045.PMID9197268.{{cite journal}}: CS1 maint: overridden setting (link)
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".Neurology.86 (6):566–576.doi:10.1212/WNL.0000000000002350.PMID26764028.
Robakis D, Fahn S (June 2015). "Defining the Role of the Monoamine Oxidase-B Inhibitors for Parkinson's Disease".CNS Drugs.29 (6):433–441.doi:10.1007/s40263-015-0249-8.PMID26164425.
Singh A, Tripathi P, Singh S (2021). "Neuroinflammatory responses in Parkinson's disease: relevance of Ibuprofen in therapeutics".Inflammopharmacology.29 (1):5–14.doi:10.1007/s10787-020-00764-w.PMID33052479.
Tan E, Chao Y, West A, Chan L, Poewe W, Jankovic J (April 2020). "Parkinson disease and the immune system - associations, mechanisms and therapeutics".Nature Reviews Neurology.16 (6):303–318.doi:10.1038/s41582-020-0344-4.PMID32332985.
Tanner CM, Ostrem JL (August 2024). "Parkinson's Disease".New England Journal of Medicine.391 (5):442–452.doi:10.1056/NEJMra2401857.PMID39083773.
Wilcox SK (January 2010). "Extending palliative care to patients with Parkinson's disease".British Journal of Hospital Medicine.71 (1):26–30.doi:10.12968/hmed.2010.71.1.45969.PMID20081638.
Zhu M, Li M, Ye D, Jiang W, Lei T, Shu K (March 2016). "Sensory symptoms in Parkinson's disease: Clinical features, pathophysiology, and treatment".Journal of Neuroscience Research.94 (8):685–692.doi:10.1002/jnr.23729.PMID26948282.
Macur J (26 March 2008)."For the Phinney Family, a Dream and a Challenge".The New York Times.Archived from the original on 6 November 2014. Retrieved25 May 2013.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 few.
"Michael's Story".The Michael J. Fox Foundation for Parkinson's Research. Retrieved7 May 2023.
.jpg)
.jpg)
