parkinson's disease parkinson's disease parkinson's disease (pd), or simply parkinson's, is a chronic 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. early symptoms are tremor, rigidity, slowness of movement, and difficulty with walking. problems may also arise with cognition, behaviour, sleep, and sensory systems. parkinson's disease dementia becomes common in advanced stages of the disease. parkinson's diseaseother namesparkinson disease, idiopathic or primary parkinsonism, hypokinetic rigid syndrome, paralysis agitans, shaking palsyillustration of parkinson's disease by william richard gowers, first published in a manual of diseases of the nervous system (1886), and based on 1879 photographs attributed to albert londespecialtyneurologysymptomstremor, rigidity, slowness of movement, difficulty walkingcomplicationsdementia, depression, anxiety, eating problems, and sleep problemsusual onsetage over 60causesunknownrisk factorspesticide exposure, head injuriesdiagnostic methodbased on symptomsdifferential diagnosisdementia with lewy bodies, progressive supranuclear palsy, essential tremor, antipsychotic usetreatmentmedications, surgerymedicationl-dopa, dopamine agonistsprognosislife expectancy about 7–15 yearsfrequency6.2 million (2015)deaths117,400 (2015) the motor symptoms of the disease result from the death of nerve cells in the substantia nigra, a region of the midbrain that supplies dopamine to the basal ganglia. the cause of this cell death is poorly understood, but involves the aggregation of the protein alpha-synuclein into lewy bodies within the neurons. collectively, the main motor symptoms are known as parkinsonism or a parkinsonian syndrome. the cause of pd is unknown, but a combination of genetic and environmental factors are believed to play a role. those with an affected family member are at an increased risk of getting the disease, with certain genes known to be inheritable risk factors. environmental risks include exposure to pesticides, and prior head injuries; a history of exposure to trichloroethylene is also suspected. conversely, caffeine and nicotine appear to be protective. diagnosis is mainly based on symptoms, with motor symptoms being the most frequently presented. tests such as neuroimaging (magnetic resonance imaging or imaging to look at dopamine neuronal dysfunction known as dat scan) are used to help rule out other diseases. parkinson's disease typically occurs in people over the age of 60, of whom about one percent are affected. males are affected at a ratio of around 3:2 compared with females. when it is seen in people before the age of 50, it is called early-onset pd. by 2015, pd affected 6.2 million people and resulted in about 117,400 deaths globally. the number of people with pd older than fifty is expected to double by 2030. the average life expectancy following diagnosis is 7–15 years. no cure for pd is known; treatment aims to reduce the effects of the symptoms. initial treatment is typically with the medications levodopa (l-dopa), mao-b inhibitors, or dopamine agonists. as the disease progresses, these medications become less effective, while at the same time producing a side effect marked by involuntary muscle movements. at that time, medications may be used in combination and doses may be increased. diet and certain forms of rehabilitation have shown some effectiveness at improving symptoms. surgery to place microelectrodes for deep brain stimulation has been used to reduce severe motor symptoms where drugs are ineffective. evidence for treatments for the nonmovement-related symptoms of pd, such as sleep disturbances and emotional problems, is less strong. the disease is named after english doctor james parkinson, who published the first detailed description in an essay on the shaking palsy, in 1817. public awareness campaigns include world parkinson's day (on 11 april, the birthday of james parkinson) and the use of a red tulip as the symbol of the disease. 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. classification parkinson's disease is the most common form of parkinsonism and is also called idiopathic parkinsonism, meaning that it has no identifiable cause. the accumulation of a misfolded protein alpha-synuclein in the brain, and its spread throughout the brain makes parkinson's disease a neurodegenerative disease classed as a synucleinopathy, and more specifically as an alpha-synucleinopathy (αsynucleinopathy). other parkinson-plus syndromes can have similar movement symptoms but have a variety of associated symptoms. some of these are also synucleinopathies. lewy body dementia involves motor symptoms with early onset of cognitive dysfunction and hallucinations which precede motor symptoms. alternatively, multiple systems atrophy or msa usually has early onset of autonomic dysfunction (such as orthostasis), and may have autonomic predominance, cerebellar symptom predominance, or parkinsonian predominance. other parkinson-plus syndromes involve tau, rather than alpha-synuclein. these include progressive supranuclear palsy (psp) and corticobasal syndrome (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. these presentation timelines and associated symptoms can help differentiate these similar movement disorders from idiopathic parkinson disease. signs and symptoms handwriting of a person affected by pd main article: signs and symptoms of parkinson's disease the most recognizable symptoms are movement (motor) related, and include tremor, bradykinesia, rigidity, and shuffling/stooped gait. 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 may be present as well. patients may have nonmotor symptoms that precede the onset of motor symptoms including constipation, anosmia, and rem behavior disorder. generally, symptoms such as dementia, psychosis, orthostasis, and more severe falls occur later. dysphagia can begin at any time during the course of parkinson's, and affects more than 80% of patients. motor further information: parkinsonism four motor symptoms are considered as cardinal signs in pd: tremor, slowness of movement (bradykinesia), rigidity, and postural instability. 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. it typically appears in only one hand, eventually affecting both hands as the disease progresses. frequency of pd tremor is between 4–6 hertz (cycles per second). a common characteristic of tremor is pill-rolling, the tendency of the index finger and thumb to touch and perform together with a circular movement. the term derives from the similarity between the movement of people with pd and the early pharmaceutical technique of manually making pills. bradykinesia 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, presenting as 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 ride a bicycle or climb stairs more easily than walk on the level. although most physicians may readily notice bradykinesia, formal assessment requires persons to do repetitive movements with their fingers and feet. in parkinsonism, rigidity or hypokinesia can be uniform, known as lead-pipe rigidity, or ratcheted, known as cogwheel rigidity. the combination of tremor and increased tone is considered to be at the origin of cogwheel rigidity. rigidity may be associated with joint pain; such pain being a frequent initial manifestation of the disease. in early stages of pd, rigidity is asymmetrical and tends to affect the neck and shoulder muscles before the muscles of the face and extremities. 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, and secondarily to bone fractures, loss of confidence, and reduced mobility. instability is absent in the initial stages, especially in younger people, especially before the development of bilateral symptoms. 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. 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. cognitive pd causes neuropsychiatric disturbances ranging from mild to severe including disorders of cognition, mood, behavior, and thought. cognitive disturbances can occur in the early stages or before diagnosis, and increase in prevalence with duration of the disease. 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. other cognitive difficulties include slowed cognitive processing speed, impaired recall, and impaired perception and estimation of time. nevertheless, improvement appears when recall is aided by cues. visuospatial difficulties are a 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. a person with pd has two to six times the risk of dementia compared with the general population. up to 78% of people with pd have parkinson's disease dementia. the prevalence of dementia increases with age, and to a lesser degree, duration of the 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. psychosis psychosis can be considered a symptom with a prevalence at its widest range from 26 to 83%. hallucinations or delusions occur in about 50% of people with pd over the course of the illness, and may herald the emergence of dementia. these range from minor hallucinations – sense of passage (something quickly passing beside the person) or sense of presence (the perception of something or someone standing to the side or behind the person) – to full blown vivid, formed visual hallucinations and paranoid ideation. auditory hallucinations are uncommon in pd, and are rarely described as voices. psychosis is believed to be an integral part of the disease. a psychosis with delusions and associated delirium is a recognized complication of anti-parkinson drug treatment. urinary tract infections (frequent in the elderly) and underlying brain pathology or changes in neurotransmitters or their receptors (e.g., acetylcholine, serotonin) are thought to play a role in psychosis in pd. neuropsychiatric behavior and mood alterations are more common in pd without cognitive impairment than in the general population and are usually present in pd with dementia. the most frequent mood difficulties are depression, apathy, and anxiety. depression impacts an estimated 20% to 35% of patients, and may appear at any stage of the disease. it can manifest with symptoms common to the disease process (fatigue, insomnia, and difficulty with concentration), which makes diagnosis difficult. the imbalance and changes in dopamine, serotonin, and noradrenergic hormones and functional imparment are causes of depression in pd-affected people. suicidal ideation is higher than in the general population, but suicidal attempts themselves are lower. risk factors for depression include disease onset under age 50, being female, previous history of depression, or severe motor symptoms. anxiety has been estimated to have a prevalence in pd-affected people usually around 30–40% and up to 60% has been found. anxiety with pd is complex and consists of symptoms specific to pd. anxiety can be higher during motor "off" periods (times when medication is ineffective) and is likely to be diagnosed after diagnosis due to dysfunction of neurotransmitter pathways. pd-affected people experience panic attacks more frequently compared with the general population. both anxiety and depression have been found to be associated with decreased quality of life. symptoms can range from mild and episodic to chronic with potential causes being abnormal gamma-aminobutyric acid levels and embarrassment or fear about symptoms or disease. risk factors for anxiety in pd are disease onset under age 50, women, and off periods. no standard treatment for pd-associated anxiety exists. apathy and anhedonia can be defined as a loss of motivation and an impaired ability