Exercise in middle age may reduce the risk of Parkinson's disease later in life. Caffeine also appears protective with a greater decrease in risk occurring with a larger intake of caffeinated beverages such as coffee. 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.

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. The results regarding fat and fatty acids have been contradictory, with various studies reporting protective effects, risk-increasing effects or no effects. There have been preliminary indications that the use of anti-inflammatory drugs and calcium channel blockers may be protective. 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.

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.

Low concentrations of urate in the blood serum is associated with an increased risk of PD.

An average clinical profile from published studies shows that the median onset age for HDLS patients is 44.3 years with a mean disease duration of 5.8 years and mean age of death at 53.2 years. As of 2012, there have been around 15 cases identified with at least 11 sporadic cases of HDLS. HDLS cases have been located in Germany, Norway, Sweden, and the United States, showing an international distribution focusing between Northern Europe and the United States.

Through the study of numerous kindred, it was found that the disease did not occur among just males or females, but rather was evenly distributed indicative of an autosomal rather than a sex-linked genetic disorder. It was also observed that the HDLS cases did not skip generations as it would occur with a recessive inheritance, and as such has been labeled autosomal dominant.

Parkinson-plus syndromes are usually more rapidly progressive and less likely to respond to antiparkinsonian medication than PD. However, the additional features of the diseases may respond to medications not used in PD.

Current therapy for Parkinson-plus syndromes is centered around a multidisciplinary treatment of symptoms.

These disorders have been linked to pesticide exposure.

The Huntington's disease-like syndromes (often abbreviated as HD-like or "HDL" syndromes) are a family of inherited neurodegenerative diseases that closely resemble Huntington's disease (HD) in that they typically produce a combination of chorea, cognitive decline or dementia and behavioural or psychiatric problems.

The prognosis and rate of the diseases progression vary considerably among individual patients and genetic kindreds, ranging from life expectancies of several months to several years, and, in exceptional cases, as long as two decades.

The prevalence and incidence remain unknown but FTDP-17 is an extremely rare condition. It is caused by mutations in the MAPT gene, which encodes a microtubule-binding protein. Over 100 families with 38 different mutations in the tau gene have been identified worldwide. The phenotype of FTDP-17 varies not only between families carrying different mutations but also between and within families carrying the same mutations.

HDL1 is an unusual, autosomal dominant familial prion disease. Only described in one family, it is caused by an eight-octapeptide repeat insertion in the "PRNP" gene. More broadly, inherited prion diseases in general can mimic HD.

In terms of frequency, is estimated at 2 per 100,000, it has identified in different regions of the world. Some clusters of certain types of autosomal dominant cerebellar ataxia reach a prevalence of 5 per 100,000.

Tauopathy belongs to a class of neurodegenerative diseases associated with the pathological aggregation of tau protein in neurofibrillary or gliofibrillary tangles in the human brain. Tangles are formed by hyperphosphorylation of a microtubule-associated protein known as tau, causing it to aggregate in an insoluble form. (These aggregations of hyperphosphorylated tau protein are also referred to as paired helical filaments). The precise mechanism of tangle formation is not completely understood, and it is still controversial as to whether tangles are a primary causative factor in the disease or play a more peripheral role. Primary tauopathies, i.e., conditions in which neurofibrillary tangles (NFT) are predominantly observed, include:

- Primary age-related tauopathy (PART)/Neurofibrillary tangle-predominant senile dementia, with NFTs similar to AD, but without plaques.

- Chronic traumatic encephalopathy, including dementia pugilistica

- Progressive supranuclear palsy

- Corticobasal degeneration

- Frontotemporal dementia and parkinsonism linked to chromosome 17

- Lytico-Bodig disease (Parkinson-dementia complex of Guam)

- Ganglioglioma and gangliocytoma

- Meningioangiomatosis

- Postencephalitic parkinsonism

- Subacute sclerosing panencephalitis

- As well as lead encephalopathy, tuberous sclerosis, Hallervorden-Spatz disease, and lipofuscinosis

Neurofibrillary tangles were first described by Alois Alzheimer in one of his patients suffering from Alzheimer's disease (AD), which is considered a secondary tauopathy. AD is also classified as an amyloidosis because of the presence of senile plaques.

The degree of NFT involvement in AD is defined by Braak stages. Braak stages I and II are used when NFT involvement is confined mainly to the transentorhinal region of the brain, stages III and IV when there's also involvement of limbic regions such as the hippocampus, and V and VI when there's extensive neocortical involvement. This should not be confused with the degree of senile plaque involvement, which progresses differently.

In both Pick's disease and corticobasal degeneration, tau proteins are deposited as inclusion bodies within swollen or "ballooned" neurons.

Argyrophilic grain disease (AGD), another type of dementia, is marked by an abundance of argyrophilic grains and coiled bodies upon microscopic examination of brain tissue. Some consider it to be a type of Alzheimer's disease. It may co-exist with other tauopathies such as progressive supranuclear palsy and corticobasal degeneration, and also Pick's disease.

Huntington's disease (HD): a neurodegenerative disease caused by a CAG tripled expansion in the Huntington gene is the most recently described tauopathy (Fernandez-Nogales et al. Nat Med 2014). JJ Lucas and co-workers demonstrate that, in brains with HD, tau levels are increased and the 4R/3R balance is altered. In addition, the Lucas study shows intranuclear insoluble deposits of tau; these "Lucas' rods" were also found in brains with Alzheimer's disease.

Tauopathies are often overlapped with synucleinopathies, possibly due to interaction between the synuclein and tau proteins.

The non-Alzheimer's tauopathies are sometimes grouped together as "Pick's complex" due to their association with frontotemporal dementia, or frontotemporal lobar degeneration.

Parkinson-plus syndromes, also known as disorders of multiple system degeneration, is a group of neurodegenerative diseases featuring the classical features of Parkinson's disease (tremor, rigidity, akinesia/bradykinesia, and postural instability) with additional features that distinguish them from simple idiopathic Parkinson's disease (PD). Some consider Alzheimer's disease to be in this group. Parkinson-plus syndromes are either inherited genetically or occur sporadically.

The atypical parkinsonian or Parkinson-plus syndromes are often difficult to differentiate from PD and each other. They include multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). Dementia with Lewy bodies (DLB), may or may not be part of the PD spectrum, but it is increasingly recognized as the second-most common type of neurodegenerative dementia after Alzheimer's disease. These disorders are currently lumped into two groups, the synucleinopathies and the tauopathies. They may coexist with other pathologies.

Additional Parkinson-plus syndromes include Pick's disease and olivopontocerebellar atrophy. The latter is characterized by ataxia and dysarthria, and may occur either as an inherited disorder or as a variant of multiple system atrophy. MSA is also characterized by autonomic failure, formerly known as Shy–Drager syndrome.

Clinical features that distinguish Parkinson-plus syndromes from idiopathic PD include symmetrical onset, a lack of or irregular resting tremor, and a reduced response to dopaminergic drugs (including levodopa). Additional features include bradykinesia, early-onset postural instability, increased rigidity in axial muscles, dysautonomia, alien limb syndrome, supranuclear gaze palsy, apraxia, involvement of the cerebellum including the pyramidal cells, and in some instances significant cognitive impairment.

HDLS falls under the category of brain white matter diseases called leukoencephalopathies that are characterized by some degree of white matter dysfunction. HDLS has white matter lesions with abnormalities in myelin sheath around axons, where the causative influences are being continually explored based upon recent genetic findings. Studies by Sundal and colleagues from Sweden showed that a risk allele in Caucasians may be causative because cases identified have thus far been among large Caucasian families.

Prognosis strongly depends on which subtype of disease it is. Some are deadly in infancy but most are late onset and mostly manageable.

Kufor–Rakeb syndrome is an autosomal recessive disorder of juvenile onset also known as Parkinson disease-9 (PARK9).

Symptoms include supranuclear gaze palsy, spasticity, and dementia.

It can be associated with "ATP13A2". It is named after Kufr Rakeb in Irbid, Jordan.

Differentiating some kinds of atypical Parkinson: Northwest Parkinson Foundation

Before Parkinson's disease is diagnosed, the differential diagnoses include:

- AIDS can sometimes lead to the symptoms of secondary parkinsonism, due to commonly causing dopaminergic dysfunction. Indeed, parkinsonism can be a presenting feature of HIV infection.

- Corticobasal degeneration

- Creutzfeldt–Jakob disease

- Dementia pugilistica or "boxer's dementia" is a condition that occurs in athletes due to chronic brain trauma.

- Diffuse Lewy body disease

- Drug-induced parkinsonism ("pseudoparkinsonism") due to drugs such as antipsychotics, metoclopramide, sertraline, fluoxetine or the toxin MPTP

- Encephalitis lethargica

- Essential tremor, an illness which has some diagnostic overlap with Parkinson's disease

- Orthostatic tremor

- MDMA addiction and frequent use has been linked to Parkonsonism. Several cases have been reported where individuals are diagnosed with the syndrome after taking MDMA.

- Multiple system atrophy

- Pantothenate kinase-associated neurodegeneration, also known as neurodegeneration with brain iron accumulation or Hallervorden-Spatz syndrome

- Parkinson plus syndrome

- Progressive supranuclear palsy

- Toxicity due to substances such as carbon monoxide, carbon disulfide, manganese, paraquat, mercury, hexane, rotenone, Annonaceae, and toluene (inhalant abuse: "huffing")

- Vascular parkinsonism, associated with underlying cerebrovascular disease

- Wilson's disease is a genetic disorder in which an abnormal accumulation of copper occurs. The excess copper can lead to the formation of a copper-dopamine complex, which leads to the oxidation of dopamine to aminochrome. The most common manifestations include bradykinesia, cogwheel rigidity and a lack of balance.

- Paraneoplastic syndrome: neurological symptoms caused by antibodies associated with cancers

- Genetic

- Rapid onset dystonia parkinsonism

- Parkin mutation

- X-linked dystonia parkinsonism

- Autosomal recessive juvenile parkinsonism

Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia, rigidity, and postural instability. Parkinsonism is found in Parkinson's disease (after which it is named), however a wide range of other causes may lead to this set of symptoms, including some toxins, a few metabolic diseases, and a handful of neurological conditions other than Parkinson's disease.

About 7% of people with parkinsonism have developed their symptoms following treatment with particular medications. Side effect of medications, mainly neuroleptic antipsychotics especially the phenothiazines (such as perphenazine and chlorpromazine), thioxanthenes (such as flupenthixol and zuclopenthixol) and butyrophenones (such as haloperidol), piperazines (such as ziprasidone), and rarely, antidepressants. The incidence of drug-induced parkinsonism increases with age. Drug-induced parkinsonism tends to remain at its presenting level, not progress like Parkinson's disease.

In terms of the genetics of autosomal dominant cerebellar ataxia 11 of 18 known genes are caused by repeated expansions in corresponding proteins, sharing the same mutational mechanism. SCAs can be caused by conventional mutations or large rearrangements in genes that make glutamate and calcium signaling, channel function, tau regulation and mitochondrial activity or RNA alteration.

The mechanism of Type I is not completely known, however Whaley, et al. suggest the polyglutamine product is toxic to the cell at a protein level, this effect may be done by transcriptional dysregulation and disruption of calcium homeostasis which causes apoptosis to occur earlier.

Desmin-related myofibrillar myopathy is a subgroup of the myofibrillar myopathy diseases and is the result of a mutation in the gene that codes for desmin which prevents it from forming protein filaments, instead forming aggregates of desmin and other proteins throughout the cell.

The exact mechanisms of these diseases are not well understood. GNE/MNK a key enzyme in the sialic acid biosynthetic pathway, and loss-of-function mutations in GNE/MNK may lead to a lack of sialic acid, which in turn could affect sialoglycoproteins. GNE knockout mice show problems similar to people with IBM and in people with IBM dystroglycan has been found to lack sialic acid. However, the part of the dystroglycan that is important in muscle function does not seem to be affected. Another protein, neural cell adhesion molecule is under-sialyated in people with IBM, but as of 2016 it had no known role in muscle function.

Autosomal dominant porencephaly type I is rare and its prevalence and incidence are unknown. It affects males and females equally.

Genetic disorders may also be complex, multifactorial, or polygenic, meaning they are likely associated with the effects of multiple genes in combination with lifestyles and environmental factors. Multifactorial disorders include heart disease and diabetes. Although complex disorders often cluster in families, they do not have a clear-cut pattern of inheritance. This makes it difficult to determine a person’s risk of inheriting or passing on these disorders. Complex disorders are also difficult to study and treat, because the specific factors that cause most of these disorders have not yet been identified. Studies which aim to identify the cause of complex disorders can use several methodological approaches to determine genotype-phenotype associations. One method, the genotype-first approach, starts by identifying genetic variants within patients and then determining the associated clinical manifestations. This is opposed to the more traditional phenotype-first approach, and may identify causal factors that have previously been obscured by clinical heterogeneity, penetrance, and expressivity.

On a pedigree, polygenic diseases do tend to "run in families", but the inheritance does not fit simple patterns as with Mendelian diseases. But this does not mean that the genes cannot eventually be located and studied. There is also a strong environmental component to many of them (e.g., blood pressure).

- asthma

- autoimmune diseases such as multiple sclerosis

- cancers

- ciliopathies

- cleft palate

- diabetes

- heart disease

- hypertension

- inflammatory bowel disease

- intellectual disability

- mood disorder

- obesity

- refractive error

- infertility

It is associated with LAMP2. The status of this condition as a GSD has been disputed.

Different people are affected very differently by this disease. The main manifestation is fluid-filled cysts that grow on the brain and can cause damage that varies depending on their location and severity. Symptoms may manifest early in infancy, or may manifest as late as adulthood. Symptoms associated with autosomal dominant porencephaly type I include migraines, hemiplegia or hemiparesis, seizures, cognitive impairment, strokes, dystonia, speech disorders, involuntary muscle spasms, visual field defects, and hydrocephalus.

Hereditary motor and sensory neuropathies are relatively common and are often inherited with other neuromuscular conditions, and these co morbidities cause an accelerated progression of the disease.

Most forms HMSN affects males earlier and more severely than females, but others show no predilection to either sex. HMSN affects all ethnic groups. With the most common forms having no racial prediliections, but other recessively inherited forms tend to impact specific ethnic groups. Onset of HMSN in most common in early childhood, with clinical effects occurring before the age of 10, but some symptoms are lifelong and progress slowly. Therefore, these symptoms do not appear until later in life.

Because lack of sialic acid appears to be part of the pathology of IBM caused by GNE mutations, clinical trials with sialic acid supplements, and with a precursor of sialic acid, N-Acetylmannosamine, have been conducted, and as of 2016 further trials were planned.