Parkinson's disease (PD), or simply Parkinson's,[9] is a long-term degenerative disorder of the central

nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the
disease worsens, non-motor symptoms become more common.[1][4] The most obvious early symptoms
are tremor, rigidity, slowness of movement, and difficulty with walking.[1] Cognitive and behavioral
problems may also occur with depression, anxiety, and apathy occurring in many people with PD.[10]
Parkinson's disease dementia becomes common in the advanced stages of the disease. Those with
Parkinson's can also have problems with their sleep and sensory systems.[1][2] The motor symptoms of
the disease result from the death of cells in the substantia nigra, a region of the midbrain, leading to a
dopamine deficit.[1] The cause of this cell death is poorly understood, but involves the build-up of
misfolded proteins into Lewy bodies in the neurons.[11][4] Collectively, the main motor symptoms are
also known as parkinsonism or a parkinsonian syndrome.[4]

The cause of PD is unknown, with both inherited and environmental factors believed to play a role.[4]
Those with an affected family member are at an increased risk of getting the disease, with certain genes
known to be inheritable risk factors.[12] Other risk factors are those who have been exposed to certain
pesticides and who have prior head injuries. Coffee drinkers, tea drinkers, and tobacco smokers are at a
reduced risk.[4][13]

Diagnosis of typical cases is mainly based on symptoms, with motor symptoms being the chief
complaint. Tests such as neuroimaging (magnetic resonance imaging or imaging to look at dopamine
neuronal dysfunction known as DaT scan) can be used to help rule out other diseases.[14][1] Parkinson's
disease typically occurs in people over the age of 60, of whom about one percent are affected.[1][3]
Males are more often affected than females at a ratio of around 3:2.[4] When it is seen in people before
the age of 50, it is called early-onset PD.[15] By 2015, PD affected 6.2 million people and resulted in
about 117,400 deaths globally.[7][8] The average life expectancy following diagnosis is between 7 and
15 years.[2]

No cure for PD is known; treatment aims to reduce the effects of the symptoms.[1][16] Initial treatment
is typically with the medications levodopa (L-DOPA), MAO-B inhibitors, or dopamine agonists.[14] As the
disease progresses, these medications become less effective, while at the same time producing a side
effect marked by involuntary muscle movements.[2] At that time, medications may be used in
combination and doses may be increased.[14] Diet and certain forms of rehabilitation have shown some
effectiveness at improving symptoms.[17][18] Surgery to place microelectrodes for deep brain
stimulation has been used to reduce motor symptoms in severe cases where drugs are ineffective.[1]
Evidence for treatments for the nonmovement-related symptoms of PD, such as sleep disturbances and
emotional problems, is less strong.[4]

The disease is named after English doctor James Parkinson, who published the first detailed description
in An Essay on the Shaking Palsy, in 1817.[19][20] Public awareness campaigns include World
Parkinson's Day (on the birthday of James Parkinson, 11 April) and the use of a red tulip as the symbol of
the disease.[21] People with PD who have increased the public's awareness of the condition include
boxer Muhammad Ali, comedian Billy Connolly, actor Michael J. Fox, Olympic cyclist Davis Phinney, and
actor Alan Alda.[22][23][24][25]

Classification

Parkinson's disease is the most common form of parkinsonism and is sometimes called "idiopathic
parkinsonism", meaning parkinsonism with no identifiable cause.[16][26] It is sometimes referred to as a
type of neurodegenerative disease called synucleinopathy due to an abnormal accumulation of the
protein alpha-synuclein in the brain.[27] The synucleinopathy classification distinguishes it from
neurodegenerative diseases such as Alzheimer's disease where the brain accumulates a different protein
known as the tau protein.[27]

Considerable clinical and pathological overlap exists between tauopathies and synucleinopathies, but
differences exist. In contrast to PD, people with Alzheimer's most commonly experience memory loss.
The cardinal signs of PD (slowness, tremor, stiffness, and postural instability) are not normal features of
Alzheimer's.

Attempts to classify PD into different subtypes have been made, with focus put on age at onset,
progression of symptoms and dominance of tremor, but none have been adopted.[28]

Signs and symptoms

Black and white picture of a male with PD stooping forward as he walks. He is viewed from the left side
with a chair behind him.

A man with PD displaying a flexed walking posture pictured in 1892[29]

French signature reads "Catherine Metzger 13 Octobre 1869"

Handwriting of a person affected by PD[30]

Main article: Signs and symptoms of Parkinson's disease

The most recognizable early symptoms are movement ("motor") related.[31] Non-motor symptoms,
including autonomic dysfunction (dysautonomia), neuropsychiatric problems (mood, cognition, behavior
or thought alterations), and sensory (especially altered sense of smell) and sleep difficulties, are usually
associated with later stages, but may present at the time of diagnosis.[31]

Motor

Further information: Parkinsonism

Four motor symptoms are considered as cardinal signs in PD: tremor, slowness of movement
(bradykinesia), rigidity, and postural instability.[31]

The most common presenting sign is a coarse, slow tremor of the hand at rest, which disappears during
voluntary movement of the affected arm and in the deeper stages of sleep.[31] It typically appears in
only one hand, eventually affecting both hands as the disease progresses.[31] Frequency of PD tremor is
between 4 and 6 hertz (cycles per second). A feature of tremor is "pill-rolling", the tendency of the index
finger and thumb to touch and perform together with a circular movement.[31][32] The term derives
from the similarity between the movement of people with PD and the early pharmaceutical technique of
manually making pills.[32]

Bradykinesia is found in every case of PD, and is due to disturbances in motor planning of movement
initiation, and associated with difficulties along the whole course of the movement process, from
planning to initiation to execution of a movement. Performance of sequential and simultaneous
movement is impaired. Bradykinesia is the most handicapping symptom of Parkinson's disease, leading
to difficulties with everyday tasks such as dressing, feeding, and bathing. It leads to particular difficulty in
carrying out two independent motor activities at the same time, and can be made worse by emotional
stress or concurrent illnesses. Paradoxically, people with PD can often ride a bicycle or climb stairs more
easily than walk on the level. While most physicians may readily notice bradykinesia, formal assessment
requires persons to do repetitive movements with their fingers and feet.[33]

Rigidity is stiffness and resistance to limb movement caused by increased muscle tone, an excessive and
continuous contraction of muscles.[31] In parkinsonism, the rigidity can be uniform, known as 'lead-pipe
rigidity', or ratchet-y, known as 'cogwheel rigidity'.[16][31][34][35] The combination of tremor and
increased tone is considered to be at the origin of cogwheel rigidity.[36] Rigidity may be associated with
joint pain; such pain being a frequent initial manifestation of the disease.[31] In early stages of PD,
rigidity is often asymmetrical and tends to affect the neck and shoulder muscles prior to the muscles of
the face and extremities.[37] With the progression of the disease, rigidity typically affects the whole
body and reduces the ability to move.

Postural instability is typical in the later stages of the disease, leading to impaired balance and frequent
falls,[38] and secondarily to bone fractures, loss of confidence, and reduced mobility.[39] Instability is
often absent in the initial stages, especially in younger people, especially prior to the development of
bilateral symptoms.[40] Up to 40% of people diagnosed with PD may experience falls, and around 10%
may have falls weekly, with the number of falls being related to the severity of PD.[31]
Other recognized motor signs and symptoms include gait and posture disturbances such as festination
(rapid shuffling steps and a forward-flexed posture when walking with no flexed arm swing). Other
common signs include freezing of gait (brief arrests when the feet seem to get stuck to the floor,
especially on turning or changing direction), a slurred, monotonous, quiet voice, mask-like facial
expression, and handwriting that gets smaller and smaller.[41]

Neuropsychiatric

PD causes neuropsychiatric disturbances ranging from mild to severe. They include disorders of
cognition, mood, behavior, and thought.[31] Cognitive disturbances can occur in the early stages or
sometimes prior to diagnosis, and increase in prevalence with duration of the disease.[31][42] The most
common cognitive deficit is executive dysfunction, which can include problems with planning, cognitive
flexibility, abstract thinking, rule acquisition, inhibiting inappropriate actions, initiating appropriate
actions, working memory, and control of attention.[42][43] Other cognitive difficulties include slowed
cognitive processing speed, impaired recall, and impaired perception and estimation of time.[42][43]
Nevertheless, improvement appears when recall is aided by cues.[42] Visuospatial difficulties are also
part of the disease, seen for example when the individual is asked to perform tests of facial recognition
and perception of the orientation of drawn lines.[42][43]

A person with PD has two to six times the risk of dementia compared to the general population.[31][42]
Up to 78% of people with PD have Parkinson's disease dementia.[44] The prevalence of dementia
increases with age, and to a lesser degree, duration of the disease.[45] 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.[42]

Impulse-control disorders, including pathological gambling, compulsive sexual behavior, binge eating,
compulsive shopping, and reckless generosity, can be caused by medication, particularly orally active
dopamine agonists. The dopamine dysregulation syndrome – with wanting of medication leading to
overuse – is a rare complication of levodopa use.[46]

Punding, in which complicated, repetitive, aimless, stereotyped behaviors occur for many hours, is
another disturbance caused by anti-Parkinson medication.