Causes and Risk Factors of Parkinson's Disease

There are several known causes of Parkinson's disease (PD). This condition is associated with decreased amounts of dopamine in a small area of the brain called the substantia nigra and in its projections to the basal ganglia (deep nuclei inside the brain).

The triggers for these changes are not completely clear, but most likely, they are secondary to an interaction between genetic and environmental factors. There are several theories about what initiates the changes of PD, and inflammation or toxins have been suggested. 

This article discusses common causes and risk factors of Parkinson's disease.

Common Causes

There is a link between the decrease in dopamine, the brain degeneration, and the Lewy body accumulation of PD, but it isn’t clear if one of these problems occurs first and causes the others, or if they are all caused by another disease trigger. 

Deficiency in Dopamine 

The most direct cause of PD symptoms is a lack of dopamine. This chemical is a neurotransmitter, which means that it sends signals to neurons.

Dopamine modulates muscle control to help the body produce smooth physical movements. It does this by stimulating several regions of the brain that are involved in movement, collectively called the basal ganglia. 

When a person with PD has a deficit of dopamine, the results include a resting tremor, muscle rigidity, impaired balance, and an overall decrease in physical movement. Dopaminergic medications such as Sinemet (carbidopa/levodopa) and Mirapex (pramipexole) mimic the action of the deficient dopamine in the body, and these medications may be able to relieve symptoms of PD for years.

Neurodegeneration 

Another problem noted with PD is the loss of neurons in the substantia nigra, a region of the midbrain. The midbrain is part of the brainstem (the lowest part of the brain, connected to the spinal cord). The substantia nigra makes dopamine, which stimulates cells throughout the basal ganglia.

Often, the changes in the substantia nigra are visible on brain imaging tests, but not always. Treatment does not help slow down degeneration or repair it.

Lewy Bodies and Alpha-Synuclein

In addition to the dopamine deficiency and neuronal loss, PD is also associated with a buildup of intracellular inclusions inside the neurons, called Lewy bodies. Studies have shown that the Lewy bodies are made mainly of a protein called alpha-synuclein.

They are not seen in brain imaging studies but have been detected in research studies that examine the brains of people who had PD and donated their own brains to science for the purpose of research. There is no known treatment or method of removing the Lewy bodies at this time. 

In PD, Lewy bodies are found in the substantia nigra as well as other areas, including the amygdala and locus coeruleus (which are involved with emotions), the raphe nucleus (which is involved with sleep), and the olfactory nerve (which controls smell). The functions controlled by these regions can be impaired in PD, although the symptoms aren’t as noticeable as the tremors and muscle stiffness. 

Lewy bodies are also present in the brains of people who have Alzheimer’s disease and other types of dementia, and they are considered a sign of neurodegeneration.

Possible PD Triggers 

While there is definitely a deficiency of dopamine, a loss of cells in the substantia nigra, and an accumulation of Lewy bodies and alpha-synuclein in PD, the cause of these changes is not clear. Experts suggest that inflammation, which is the rise of immune cells, is at the root of this damage. Oxidation, a harmful chemical reaction, has been noted in PD. Damage to the mitochondria, the energy-producing regions of human cells, has been observed as well.

But the trigger factor that causes the inflammation, oxidation, and mitochondrial damage to happen has not been identified. Over the years, there have been many theories regarding the initial trigger, including infections or exposure to toxins. Yet no toxin or infection has been reliably linked with PD. Experts suggest that there may be a genetic predisposition to PD, combined with environmental factors. 

Causes of Parkinsonism 

Parkinsonism is a condition in which a person develops some of the symptoms of PD, but does not have PD.

There are a few known causes of parkinsonism, including:

• Atypical parkinsonism (a group of disorders exhibiting classic signs of parkinsonism, but having additional symptoms such as swallowing problems, early falls, autonomic dysfunction). There are 4 disorders in this category—progressive supranuclear palsy (PSP), multisystem atrophy (MSA), Lewy body dementia (LBD), and corticobasal degeneration (CBD).
• Antipsychotic medications, which can diminish the effects of dopamine
• A brain tumor 
• A rare and unusual infection, encephalitis lethargica
• Head trauma
• Stroke, which can affect any region of the brain (including the substantia nigra or basal ganglia)

Genetics 

There have been a number of genes identified in association with PD. Most people who develop the disease do not have a family history of the disease and are said to have sporadic PD.

Several defective genes have been linked to PD, including:

• α-synuclein (SNCA)
• Leucine-rich repeat kinase 2 (LRRK2)
• PARKIN
• PTEN-induced putative kinase 1 (PINK1)
• PARK2
• DJ-1 (Daisuke-Junko-1)
• Glucocerebrosidase beta acid (GBA)
• Microtubule-associated protein tau (MAPT)

Overall, one or more of these genes are found in about 5% to 15% of families or individuals who have PD. That said, genetic testing is not a standard part of PD treatment, and there aren’t established treatments that correspond with specific genetic defects.

Lifestyle Risk Factors

A number of habits have been weakly associated with PD. Alcohol, diet, smoking, and caffeine have all been linked with the condition, but study results regarding their degree of impact on the disease are often inconsistent. 

Smoking is the most popularly discussed lifestyle factor with PD. For years, experts have suggested that smoking may actually decrease the risk of PD. However, more recent studies suggest that having PD or a predisposition to PD prevents smoking and that smoking probably doesn’t protect against PD.

Other risk factors for the disease include heavy alcohol use and lack of physical activity. Some, but not all, studies have linked obesity—and particularly increased waist circumference—to an increased risk of PD.

Interestingly, while solvents and chemicals have often been blamed for PD, studies suggest that they do not cause the disease.