Classification

Signs and symptoms

Causes

Main article: Causes of Parkinson's disease Environmental factors Exposure to pesticides and a history of head injury have each been linked with Parkinson disease (PD), but the risks are modest. Never having smoked cigarettes, and never drinking caffeinated beverages, are also associated with small increases in risk of developing PD.[44] Low concentrations of urate in the blood serum is associated with an increased risk of PD.[48] Genetics Parkin crystal structure Research indicates that PD is the product of a complex interaction of genetic and environmental factors.[4] Around 15% of individuals with PD have a first-degree relative who has the disease,[10] and 5–10% of people with PD are known to have forms of the disease that occur because of a mutation in one of several specific genes.[49] Harboring one of these gene mutations may not lead to the disease; susceptibility factors put the individual at an increased risk, often in combination with other risk factors, which also affect age of onset, severity and progression.[49] Genes implicated in the development of PD include SNCA, LRRK2, GBA, PRKN, PINK1, PARK7, VPS35, EIF4G1, DNAJC13 and CHCHD2.[50] About 5% of people with PD have mutations in the GBA1 gene.[51] These muations are present in < 1% of the unaffected population. The risk of developing PD is increased 20-30 fold if these muations are present. PD associated with these mutations has the same clinical features but an earlier age of onset and a more rapid cognitive and motor decline. SNCA gene mutations are important in PD because the protein which this gene encodes, alpha-synuclein, is the main component of the Lewy bodies that accumulate in the brains of people with PD.[49] Mutations in some genes, including SNCA, LRRK2 and GBA, have been found to be risk factors for "sporadic" (non-familial) PD.[49] Mutations in the gene LRRK2 are the most common known cause of familial and sporadic PD, accounting for approximately 5% of individuals with a family history of the disease and 3% of sporadic cases.[52][49] A mutation in GBA presents the greatest genetic risk of developing Parkinsons disease.[50] Several Parkinson-related genes are involved in the function of lysosomes, organelles that digest cellular waste products. It has been suggested that some cases of PD may be caused by lysosomal disorders that reduce the ability of cells to break down alpha-synuclein.[53]

Pathophysiology

Diagnosis

Prevention

Exercise in middle age may reduce the risk of Parkinson's disease later in life.[12] Caffeine also appears protective with a greater decrease in risk occurring with a larger intake of caffeinated beverages such as coffee.[71] People who smoke cigarettes or use smokeless tobacco are less likely than non-smokers to develop PD, and the more they have used tobacco, the less likely they are to develop PD. It is not known what underlies this effect. Tobacco use may actually protect against PD, or it may be that an unknown factor both increases the risk of PD and causes an aversion to tobacco or makes it easier to quit using tobacco.[72] Antioxidants, such as vitamins C and E, have been proposed to protect against the disease, but results of studies have been contradictory and no positive effect has been proven.[73] The results regarding fat and fatty acids have been contradictory, with various studies reporting protective effects, risk-increasing effects or no effects.[73] There have been preliminary indications that the use of anti-inflammatory drugs and calcium channel blockers may be protective.[4] A 2010 meta-analysis found that nonsteroidal anti-inflammatory drugs (apart from aspirin), have been associated with at least a 15 percent (higher in long-term and regular users) reduction of incidence of the development of Parkinson's disease.[74]

Management

Prognosis

Epidemiology

History

Society and culture

Research