[20][21] Bradykinesia describes difficulties in motor planning, beginning, and executing, resulting in overall slowed movement with reduced amplitude that affects sequential and simultaneous tasks.

[41][42] Other autonomic failures include gastrointestinal issues like chronic constipation, impaired stomach emptying and subsequent nausea, excessive salivation, and dysphagia (difficulty swallowing): all greatly reduce quality of life.

[73] Paraquat, for instance, structurally resembles metabolized MPTP,[70] which selectively kills dopaminergic neurons by inhibiting mitochondrial complex 1 and is widely used to model PD.

[84] This theory could explain the presence of Lewy pathology in both the enteric nervous system and olfactory tract neurons, as well as clinical symptoms like loss of smell and gastrointestinal problems.

The catecholaldehyde hypothesis argues that the oxidation of dopamine by MAO into 3,4-dihydroxyphenylacetaldehyde (DOPAL) and hydrogen peroxide and the subsequent abnormal accumulation thereof leads to neurodegeneration.

[95] Additionally, influenza and herpes simplex virus infections increase the risk of PD, possibly due to a viral protein resembling alpha-synuclein.

[57] 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 the substantia nigra pars compacta.

[140] A PD diagnosis is typically confirmed by two of the following criteria: responsiveness to levodopa, resting tremor, levodopa-induced dyskinesia, or with dopamine transporter single-proton emission computed tomography.

In their initial stages, PD can be difficult to distinguish from the atypical neurodegenerative parkinsonisms, including MSA, dementia with Lewy bodies, and the tauopathies progressive supranuclear palsy and corticobasal degeneration.

[144] Key distinguishing symptoms and features include:[139][156][157] As of 2024, no disease-modifying therapies exist that reverse or slow neurodegeneration, processes respectively termed neurorestoration and neuroprotection.

[168][169] Its metabolism outside the brain by aromatic L-amino acid decarboxylase (AAAD) and catechol-O-methyltransferase (COMT) can cause nausea and vomiting; inhibitors like carbidopa, entacapone, and benserazide are usually taken with levodopa to mitigate these effects.

[175] Ergot dopamine agonists were commonly used, but have been largely replaced with non-ergot compounds due to severe adverse effects like pulmonary fibrosis and cardiovascular issues.

[203] 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, and meditation.

[204] Deep diaphragmatic breathing may also improve chest-wall mobility and vital capacity decreased by the stooped posture and respiratory dysfunctions of advanced Parkinson's.

[209] Parkinson's poses digestive problems like constipation and prolonged 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.

[214] As Parkinson's 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.

[226] Parkinson's disease dementia is associated with a reduced quality of life in people with PD and their caregivers, increased mortality, and a higher probability of needing nursing home care.

[240] Although PD incidence and prevalence may vary by race and ethnicity, significant disparities in care, diagnosis, and study participation limit generalizability and lead to conflicting results.

[242][243] In 1817, English physician James Parkinson published the first full medical description of the disease as a neurological syndrome in his monograph An Essay on the Shaking Palsy.

[247] 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 spinal cord.

[247][249] Subsequent neurologists who made early advances to the understanding of Parkinson's include Armand Trousseau, William Gowers, Samuel Kinnier Wilson, and Wilhelm Erb.

[249] Possible earlier but incomplete descriptions include a Nineteenth Dynasty Egyptian papyrus, the ayurvedic text Charaka Samhita, Ecclesiastes 12:3, and a discussion of tremors by Leonardo da Vinci.

[252] In 2009, a systematic description of PD was found in the Hungarian medical text Pax corporis written by Ferenc Pápai Páriz in 1690, some 120 years before Parkinson.

[265] 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.

[269] The duration and progressive nature of PD can place a heavy burden on caregivers:[270] family members like spouses dedicate around 22 hours per week to care.

[121][122] Active research directions include the search for new animal models of the disease and development and trial of gene therapy, stem cell transplants, and neuroprotective agents.

[299][300] Anti-alpha-synuclein drugs that prevent alpha-synuclein oligomerization and aggregation or promote their clearance are under active investigation, and potential therapeutic strategies include small molecules and immunotherapies like vaccines and monoclonal antibodies.

[313][314] Gene therapy for Parkinson's 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.

[317] Experimental gene therapies for PD have aimed to increase the expression of growth factors or enzymes involved in dopamine synthesis, like tyrosine hydroxylase.