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Parkinson’s disease (PD) is a common movement disorder affecting nearly one million people in the United States and 10 million worldwide. The death of neurons or nerve cells producing dopamine is the main cause of PD. The build-up of the protein alpha-synuclein in the brain, and occasionally in the gut, can also cause neurons to die.
The exact causes of the disorder are unclear, but researchers have identified several risk factors for Parkinson’s disease. The disease likely progresses unnoticed for many years before diagnosis, and the first signs of PD could be mistaken for other conditions or simply as part of aging.
Yet, certain diet and lifestyle factors may help with nutrition and gut health deficits often associated with PD during the early stages. Recent research also suggests there may be ways to detect PD earlier, which could help with earlier treatment and control of health effects.
Parkinson’s disease is complex and likely caused by several factors. In some cases, PD is spontaneous and develops for no clear reason.
Researchers have identified several environmental factors that may lead to the loss of nerve cells, causing a lack of dopamine. A large case-control study looked at factors that may increase the risk of or protect against developing PD. The most common environmental risks were exposure to toxins and dyspepsia.
Researchers believe that environmental factors or other medical conditions may contribute to disease development in those with or without a family history of PD. PD may also happen without any known cause for others.
The most common toxins PD patients have been exposed to include:
Heightened exposure to pesticides may lead to high alpha-synuclein levels in the brain. Contact with these toxins may result from professional or residential exposures, including rural living. Additionally, past head trauma, coffee consumption, cigarette smoking and low physical activity were associated with increased PD risk.
People who have a relative with PD have a three to four times higher risk of developing Parkinson’s disease. Genetic variations or mutations are thought to contribute an overall 25% risk.
Researchers have identified more than 90 variants of key genes mostly linked to alpha-synuclein protein coding and mitochondria or energy center function in brain cells. Common genetic variants associated with PD were also often involved in signaling pathways associated with response to a stressor, which could be a toxin.
Mutations in some of these genes cause problems with how your body uses chemical messengers like dopamine. They also alter protein buildup and the body's ability to remove unstable molecules called free radicals. In addition, changes to alpha-synuclein’s SNCA gene likely contribute to early-onset Parkinson’s disease.
Certain gut symptoms and sleep disorders are strongly associated with PD and may be risk factors for, or early signs of, Parkinson’s disease. About 80% of patients with PD have at least one digestive symptom throughout the disease, including nausea, constipation, and difficulty completing a bowel movement.
Constipation often happens before motor symptoms appear and worsens as the disease progresses. It’s considered one of the most significant prodromal (or early warning) symptoms and may occur as much as 20 years before a diagnosis.
One theory suggests PD may be linked to variations in the balance of bacteria and a buildup of alpha-synuclein aggregates in the gut that travels to the brain.
Research also suggests that a medical history of rapid eye movement sleep behavior disorder (RBD) is a powerful predictor of Parkinson’s disease. RBD is a chronic sleep disorder that causes loss of rapid eye movement (REM) sleep, resulting in sleep paralysis in which one may experience dream enactment while asleep. Patients often report high injury rates to themselves and others during sleep because of violent movements.
RBD is considered a prodromal symptom, or one of a few early signs of Parkinson’s disease. About 70% of patients with RBD will develop parkinsonism and alpha-synuclein aggregates in the brain within 12 years of diagnosis. About 40% of patients with PD also have RBD at the same time, suggesting the two conditions develop alongside each other.
Long before motor symptoms of Parkinson’s disease appear, problems in the gut and/or brain may begin setting the stage. For some people, PD may start in the gut or digestive tract, while it begins in the brain for others.
The gut and brain have a bidirectional relationship, which means the brain influences the digestive system and vice versa. Whether Parkinson’s begins in the digestive tract or the brain, most patients have symptoms in both.
The exact progression and cause of the disease aren’t clear. However, patients have common characteristics: gut dysbiosis, alpha-synuclein accumulation, and loss of dopamine-synthesizing neurons in the substantia nigra, leading to dopamine deficiency and dopamine-signaling problems.
Gut dysbiosis is the imbalance of the bacteria in your gut, known as the microbiota or microbiome. Dysbiosis is associated with a few key features, such as:
Some beneficial gut bacteria interact with your nervous system via the vagus nerve, which connects the gut and brain. Thus, microbiome changes can have an impact on brain health.
In addition, the gut barrier can break down when dysbiosis occurs, allowing bacteria byproducts and food molecules to leak into your bloodstream and potentially cross the blood-brain barrier. This can lead to inflammation in the brain, and interference with brain signaling.
Many people eventually diagnosed with PD have an altered microbiome and have gut problems before motor symptoms, such as tremors, appear. Whether or not an altered microbiome can contribute to aggregation of alpha-synuclein within the gut is not known.
Parkinson’s disease is a dopamine deficiency disease. Dopaminergic cells die due to aggregation of alpha-synuclein or other reasons. Without these cells, your body doesn't make enough dopamine, affecting your movement, memory, mood, and cognitive ability.
The degradation of common motor symptoms, like balance or fine motor control, begins to appear as the damage occurs. However, you may have experienced your first symptoms of Parkinson’s much earlier.
