Many risk factors have been proposed, sometimes in relation to theories concerning possible mechanisms of the<unk> ; however, none has been proven conclusively. The most frequently replicated relationships are an increased risk in those exposed to pesticides, and a reduced risk in smokers. A possible link exists between<unk>  and Helicobacter pylori infection that can prevent the absorption of some drugs, including levodopa. Genetic Parkin crystal structure Research indicates that<unk>  is the product of a complex interaction of genetic and environmental factors. Around 15% of individuals with<unk>  have a first-degree relative who has the<unk> , and 5–10% of people with<unk>  are known to have forms of the<unk>  that occur because of a mutation in one of several specific genes. Harboring one of these gene mutations may not lead to the<unk> ; 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. At least 11 autosomal dominant and 9 autosomal recessive gene mutations have been implicated in the development of<unk> . The autosomal dominant genes include SNCA, PARK3, UCHL1, LRRK2, GIGYF2, HTRA2, EIF4G1, TMEM230, CHCHD2, RIC3, and VPS35. Autosomal recessive genes include PRKN, PINK1, PARK7, ATP13A2, PLA2G6, FBXO7, DNAJC6, SYNJ1, and VPS13C. Some genes are X-linked or have unknown inheritance pattern; those include PARK10, PARK12, and PARK16. A 22q11 deletion is also known to be associated with<unk> . An autosomal dominant form has been associated with mutations in the LRP10 gene. About 5% of people with<unk>  have mutations in the GBA1 gene. These mutations are present in less than 1% of the unaffected population. The risk of developing<unk>  is increased 20–30 fold if these mutations are present.<unk>  associated with these mutations has the same clinical features, but an earlier age of onset and a more rapid cognitive and motor decline. This gene encodes glucocerebrosidase. Low levels of this enzyme cause Gaucher's<unk> . SNCA gene mutations are important in<unk>  because the protein this gene encodes, alpha-synuclein, is the main component of the Lewy bodies that accumulate in the brains of people with<unk> . Alpha-synuclein activates ataxia telangiectasia mutated, a major DNA damage-repair signaling kinase. In addition, alpha-synuclein activates the non-homologous end joining DNA repair pathway. The aggregation of alpha-synuclein in Lewy bodies appears to be a link between reduced DNA repair and brain-cell death in<unk> . Mutations in some genes, including SNCA, LRRK2, and GBA, have been found to be risk factors for "sporadic" (nonfamilial)<unk> . Mutations in the gene LRRK2 are the most common known cause of familial and sporadic<unk> , accounting for around 5% of individuals with a family history of the<unk>  and 3% of sporadic cases. A mutation in GBA presents the greatest genetic risk of developing<unk> . Several Parkinson-related genes are involved in the function of lysosomes, organelles that digest cellular waste products. Some cases of<unk>  may be caused by lysosomal disorders that reduce the ability of cells to break down alpha-synuclein. Non-genetic Exposure to pesticides and a history of head injury have each been linked with<unk> , but the risks are modest. Never drinking caffeinated beverages is also associated with small increases in risk of developing<unk> . Some toxins can cause parkinsonism, including manganese and carbon disulfide. Medical drugs implicated in cases of parkinsonism. Drug-induced parkinsonism is normally reversible by stopping the offending agent, such as phenothiazines (chlorpromazine, promazine, etc.); butyrophenones (haloperidol, benperidol, etc.); metoclopramide and Tetrabenazine. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a drug known for causing irreversible parkinsonism that is commonly used in animal-model research. Low concentrations of urate in the blood is associated with an increased risk of<unk> . Other identifiable causes of parkinsonism include infections and metabolic derangement. Several neurodegenerative disorders also may present with parkinsonism, and are sometimes referred to as "atypical parkinsonism" or "Parkinson plus" syndromes (illnesses with parkinsonism plus some other features distinguishing them from<unk> . They include multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, and dementia with Lewy bodies. Dementia with Lewy bodies is another synucleinopathy and it has close pathological similarities with<unk> , especially with the subset of<unk>  cases with dementia known as<unk>  dementia. The relationship between<unk>  and DLB is complex and incompletely understood. They may represent parts of a continuum, with variable distinguishing clinical and pathological features, or they may prove to be separate<unk> s. Vascular parkinsonism is the phenomenon of the presence of<unk>  symptoms combined with findings of vascular events (such as a cerebral stroke). The damaging of the dopaminergic pathways is similar in cause for both vascular parkinsonism and idiopathic<unk> , so they can present with many of the same symptoms. Differentiation can be made with careful bedside examination, history evaluation, and imaging.
Parkinson's disease
Dementia with Lewy bodies
Parkinsonism
Antipsychotic
Parkinson-plus syndrome
Essential tremor
Alzheimer's disease
Progressive supranuclear palsy