Parkinson’s Causes: Learn everything you need to know

Parkinson’s Causes. Neurotransmitters like dopamine are the body’s chemical messengers. They send signals between neurons (i.e. nerve cells) to assist with nearly all physical and psychological functions. In neurodegenerative disorders such as Parkinson’s disease, dopamine levels rapidly decline. Why do neurotransmitter levels drop? What causes Parkinson’s? This is what research has shown.

Parkinson's Causes
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What Is Parkinson’s Disease?

Parkinson’s disease is a neurodegenerative disorder of the nervous system that affects the brain’s dopamine-producing cells (also called neurons). Someone with Parkinson’s experiences both motor and non-motor symptoms. The primary motor symptoms impact movement and include resting tremor, rigidity, an unbalanced gait, and bradykinesia, while the most common non-motor symptoms are sleep disorders, mood changes, constipation, a loss of smell, autonomic dysfunction, and cognitive impairment. The condition is progressive as dopamine-producing neurons die off over time. There is no cure.

Symptoms of Parkinson’s disease are the result of reduced dopamine levels in the brain, but what causes levels of that crucial neurotransmitter to drop? It’s difficult to know with certainty, but researchers have discovered various causes and risk factors.

Parkinson’s Causes: Neurotransmitter Imbalance

With the impact Parkinson’s has on all divisions of the nervous system, brain changes are obviously at the root of Parkinson’s causes. Neurons, or brain cells, die off. As the cells are damaged, the nervous system lacks the essential neurotransmitters needed to function. Parkinson’s disease specifically targets the neurons that produce dopamine.

The body attempts to make up for the loss of dopamine by way of other neurotransmitters. For example, glutamate activity in a portion of the brain called the basal ganglia increases which damage nervous system tissue. The mechanisms of dopamine—what little remains in a Parkinson’s patient—is counteracted by acetylcholine. Lastly, norepinephrine is reduced in Parkinson’s because it relies on the same damaged nerves. The reduction of norepinephrine contributes to many of the symptoms related to autonomic dysfunction like the automatic processes of heart rate and blood pressure.

Parkinson’s Causes: Genes Versus Environment

Parkinson’s disease can be hereditary. According to the Parkinson’s Foundation, 10 to 15 percent of cases have a genetic cause.  After observing cases of Parkinson’s disease in families, researchers have identified numerus genetic mutations indicating a genetic cause for the condition.

These genes are typically in the following genes:

  • LRRK2
  • PARK7
  • PINK1
  • PRKN
  • SNCA

Genetic mutations predispose one to develop the condition. However, most experts agree that the environment also has a significant role. Environmental factors interact with a genetic predisposition to trigger the onset of the disease.

Parkinson’s Causes: Aging

The average onset of Parkinson’s disease is an age of 60 or greater—making age the number one risk factor. The brain naturally shrinks with advancing age. White matter in the brain decreases, levels of neurotransmitters and hormones change, and neurons become damaged.

Studies (Rodriguez, 2015) prove that healthy controls manifest with neurodegeneration in the same areas of the brain as those with Parkinson’s disease but to a milder extent. This is why the risk of dementia, a symptom of Parkinson’s, is higher in older age along with memory loss without the presence of dementia.

Parkinson's Causes
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Parkinson’s Causes: Gender

Men are especially prone to developing Parkinson’s disease than women. Reasons remain under speculation. Two theories are that men are exposed to environmental factors like toxin exposure, and head trauma more frequently than women due to their occupations. Another hypothesis involves the hormone estrogen. Estrogen regulates functions most impacted by Parkinson’s disease such as motor control and mood. The hormone has the ability to alter free radicals, which are molecules that damage cells in the body. Because women have higher amounts of estrogen than men, it likely serves as a protective factor that prevents dopamine-producing cells from damage.

Parkinson’s Causes: Exposure To Environmental Toxins

Environmental toxins comprise several potentially harmful chemicals that have been linked to causing Parkinson’s disease. These include herbicides, pesticides, and even heavy metals.

Trichloroethylene (TCE), a common contaminant of groundwater from the runoff of factories, has been reported to cause Parkinson’s in workers with long term exposure. Animal studies further support the adverse effects of TCE on the development of Parkinson’s. The substantia nigra is responsible for dopamine production, and TCE inhibited mitochondrial function in this area of the brain (Wiley-Blackwell, 2008).

Parkinson’s Causes: Head Trauma

Traumatic brain injury is a risk factor for Parkinson’s disease. Research on the connection between traumatic brain injury (TBI) and Parkinson’s disease began because of the boxer, Muhammad Ali, as it was speculated that his early-onset Parkinson’s diagnosis is caused by repeated trauma to the head. Twin studies have been particularly enlightening (Goldman et al., 2006). In two twins reared together, only the twin who experienced a trauma to the head developed Parkinson’s disease. 

Information on this topic is still underway. Experts have considered plausible explanations for the perceived association: 

  • The head injury may directly damage dopamine-producing neurons. 
  • The injury may indirectly damage dopamine-producing neurons by triggering an inflammatory process. 
  • The trauma interacts with genetic factors and “awakens” the onset of Parkinson’s disease in those who are already susceptible to developing the condition. 

Parkinson’s Causes: Parkinsonism

While Parkinson’s disease is a neurodegenerative disorder with motor and non-motor symptoms, parkinsonism is a category of Parkinson’s characterized by only its motor symptoms that affect movement— tremors, rigidity, involuntary movements, imbalance, and stiffness. Parkinsonism has many causes ranging from other disorders to drug-induced. Physicians must be careful to properly assess the patient to differentiate between general Parkinson’s disease and parkinsonism.

Parkinson’s Causes: Other Neurodegenerative Disorders

Other neurological and neurodegenerative conditions mimic the movement symptoms of Parkinson’s disease. The similar disorders result in Parkinsonism and can be difficult to distinguish from full Parkinson’s disease. Over time, a patient’s diagnosis may change to Parkinson’s as they progress.

  • Lewy Body Dementia—Dementia with Lewy bodies presents with the same movement symptoms as Parkinson’s, but without a tremor. The main feature is a progressive decline of cognitive function with hallucinations, memory loss, and changes in thinking.
  • Progressive Supranuclear Palsy—Like Parkinson’s, PSP begins around age 60 and includes mood changes, weakness, and imbalance. Later stages involve paralysis of the eye muscles.
  • Multiple System Atrophy—MSA presents with the autonomic symptoms of Parkinson’s such as drops in blood pressure, constipation, and bladder problems. The inability to sweat, erectile dysfunction, and speech difficulties also stem from a loss of dopamine.
  • Vascular Parkinsonism—A series of small strokes damage dopamine-producing neurons in vascular Parkinsonism. Progression is slower than in traditional Parkinson’s disease and gait problems are the prominent symptom.
  • Corticobasal Degeneration—People with CBD feel they cannot control their limbs, despite no weakness or sensory loss. They display jerky, involuntary movements.

Parkinson’s Causes: Drugs

Since Parkinson’s is caused by a lack of dopamine, drugs that block the action of dopamine can induce Parkinson’s-like symptoms as a side effect. Calcium channel blockers, antipsychotics, gastrointestinal prokinetic drugs, lithium, seizure medications, and stimulants (i.e. cocaine, amphetamine) produce tremors, abnormal or involuntary movements of the muscles, and autonomic dysfunction. Symptoms from drug-induced parkinsonism are milder than in Parkinson’s disease and abate once the drug is discontinued.

Parkinson’s Causes: Viral Parkinsonism

A virus is a harmful microscopic agent that infects healthy cells. Viruses are capable of infecting the brain. As they do, they cause inflammation in the brain known as viral encephalitis. Viral encephalitis damages the dopamine-producing nerve cells, which provokes motor symptoms such as a loss of balance, stiffness, and other abnormal movements. HIV, West Nile Virus, and the Western Equine Virus are all notable causes of parkinsonism. However, symptoms do not begin immediately at the onset of the virus. They can manifest months to years later.

Parkinson’s Causes: Structural Brain Abnormalities

Structural abnormalities in the brain are occasionally associated with Parkinson’s disease. Benign and malignant (i.e. cancerous) tumors and brain lesions interfere with the function of the basal ganglia—the main portion of the brain impacted by Parkinson’s disease. Resultantly, patients can present with a range of motor and non-motor symptoms depending on the location of the tumor and/or lesion. If the damage is not too extensive, symptoms resolve when the tumor is surgically removed in some cases. Brain imaging computerized tomography (CT) and magnetic resonance imaging (MRI) is critical for the diagnosis because they reveal any abnormalities causing symptoms.  

References

Goldman, S.M., Tanner, C.M., Oakes, D., Bhudhikanok, G.S., Gupta, A., & Langston, J.W. (2002). Head injury and Parkinson’s disease risk in twins. Ann Neurol, 60(1):65‐72. doi:10.1002/ana.20882

Rodriguez, M., Rodriguez-Sabate, C., Morales, I., Sanchez, A., & Sabate, M. (2015). Parkinson’s disease as a result of aging. Aging cell, 14(3), 293–308. https://doi.org/10.1111/acel.12312

Shin, H. W., & Chung, S. J. (2012). Drug-induced parkinsonism. Journal of clinical neurology (Seoul, Korea), 8(1), 15–21. https://doi.org/10.3988/jcn.2012.8.1.15

Wiley-Blackwell. (2008). Trichloroethylene (TCE) Is A Risk Factor For Parkinsonism, Study Shows. Retrieved from https://www.sciencedaily.com/releases/2008/01/080107181340.htm