What are the Causes and Risk Factors of Parkinson’s Disease?

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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 concerning Parkinson’s Disease aren’t completely clear. However, they are most likely 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.

Very Well Health’s recent article entitled “Causes and Risk Factors of Parkinson’s Disease” reports that there’s a link between the decrease in dopamine, the brain degeneration and the Lewy body accumulation of PD. However, it isn’t clear if one of these problems happens first and causes the others, or if they are all caused by another disease trigger.

Deficiency in Dopamine. The most direct cause of Parkinson’s Disease symptoms is insufficient dopamine, which is a neurotransmitter sending signals to neurons. Dopamine modulates muscle control to help the body produce smooth physical movements. When an individual with PD has a deficit of dopamine, they may experience 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. These medications may be able to relieve symptoms of PD for years. However, these medications don’t prevent the disease itself from worsening—brain degeneration and Lewy body accumulation continue, despite treatment with dopaminergic therapy.

Neurodegeneration. Another issue 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; this stimulates cells throughout the basal ganglia. The changes in the substantia nigra are frequently visible on brain imaging tests. However, this is not always true. Treatment also doesn’t help slow down degeneration or repair it.

Lewy Bodies and Alpha-Synuclein. PD is also associated with a buildup of intracellular inclusions inside the neurons, called Lewy bodies, which are made mainly of a protein called alpha-synuclein. They aren’t 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 located 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. They’re also present in the brains of people who have Alzheimer’s disease and other types of dementia. hey are considered a sign of neurodegeneration.

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Reference: Very Well Health (Nov. 28, 2022) “Causes and Risk Factors of Parkinson’s Disease”