- Recently published research suggests certain gastrointestinal issues could be early warning signs of Parkinson’s disease.
- Researchers compared medical records of individuals who had been diagnosed with Parkinson’s with individuals who had been diagnosed with Alzheimer’s or cerebrovascular disease or none of those diseases.
- Their analyses suggest four gut conditions may be associated with a higher risk of later receiving a diagnosis of Parkinson’s.
Researchers say they are the first to provide “substantial observational evidence” that individuals diagnosed with certain digestive issues could predict the development of Parkinson’s disease.
After conducting statistical analyses, the researchers determined four gut conditions associated with Parkinson’s:
- dysphagia (difficulty swallowing)
- gastroparesis (delayed stomach emptying)
- irritable bowel syndrome (IBS) without diarrhea
Parkinson’s disease (PD) is a progressive neurological condition. Its main symptoms are tremors, slow movement, and muscle stiffness.
The research appears in the journal Gut.
Four digestive issues linked to Parkinson’s
Researchers found that gastroparesis, dysphagia, and constipation were associated with a more than double increased risk of developing Parkinson’s disease. IBS without diarrhea was associated with a 17% higher risk.
Other gut issues, including IBS with diarrhea and diarrhea plus fecal incontinence, were also found to be more common among people later diagnosed with Parkinson’s disease as well as people later diagnosed with Alzheimer’s disease (AD) and cerebrovascular disease.
Experts have considered constipation to be a potential risk factor for Parkinson’s disease “for a very long time,” according to study co-author Dr. Pankaj J. Pasricha, chair of the department of medicine at the Mayo Clinic Arizona in Scottsdale.
“This study adds to the list of GI conditions that could potentially be risk factors,” Dr. Pasricha told Medical News Today.
In their paper, the researchers also noted they found that appendectomy is associated with a reduced risk of developing Parkinson’s.
“People have suggested that a trigger may lie in the appendix — but there obviously needs to be more work on that,” said non-study author Dr. Ted Dawson, director of the Institute for Cell Engineering and professor of neurology at Johns Hopkins University School of Medicine.
Additionally, researchers found neither inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, nor removal of all or part of the vagus nerve to treat a peptic ulcer associated with an increased risk of being diagnosed with Parkinson’s.
Dr. Pasricha said the researchers expected the findings to show a link between conditions in the gut and the development of Parkinson’s. “We were not surprised but were impressed by the strength of the association,” he said.
More evidence suggests Parkinson’s may start in the gut
Many studies have indicated that Parkinson’s disease may start in the gut.
Recently, researchers from Columbia University Irving Medical Center in New York City conducted a study in mice to examine this idea. The researchers found evidence suggesting an autoimmune response in the gut can lead to what appears to be the early stages of Parkinson’s.
The study co-authored by Dr. Pasricha is an important addition to this collection of evidence, according to Dr. Dawson.
“The data where dysphagia, gastroparesis, and irritable bowel syndrome without diarrhea might specifically predict the development of Parkinson’s disease as indicated in the conclusion is a novel and a new observation. [That] really supports the notion of Parkinson’s disease, at least in a major subset of patients, starting in the gastrointestinal tract.”
— Dr. Ted Dawson, Johns Hopkins University professor of neurology
In their paper, Dr. Pasricha and his co-authors note that links between the gut and the development of Alzheimer’s disease and cerebrovascular disease have also been proposed.
Researchers examined thousands of medical records
Researchers performed a combined case-control and cohort study using medical records from the TriNetX Analytics Research Network. Researchers undertaking a case-control study make groups of individuals who have or do not have a disease.
Cohort studies follow participants over a period of time.
Researchers analyzed the medical records of 24,624 people diagnosed with Parkinson’s disease.
They compared them with 19,046 people with Alzheimer’s, 23,952 people with cerebrovascular disease, and 24,624 people diagnosed with none of these diseases.
Researchers matched individuals diagnosed with Parkinson’s disease with people from the three other groups to look at how frequently they experienced certain gut-related troubles in the years prior to diagnosis.
Additionally, they placed adults who had been diagnosed with any of 18 gut conditions, including Crohn’s disease and appendectomy, into separate groups.
Researchers matched these adults with other adults who had not experienced the gut conditions and studied their medical records for five years to see who developed Parkinson’s disease or other neurological problems.
Theory linking Parkinson’s to gut health is two decades old
In 2003, Dr. Heiko Braak, professor at the Institute for Clinical Neuroanatomy at Johann Wolfgang Goethe University in Frankfurt, Germany, and other researchers proposed that Parkinson’s disease begins in the gut in some patients.
The theory linking gut health to Parkinson’s became known as Braak’s hypothesis.
In individuals who have Parkinson’s disease, alpha-synuclein, a protein, misfolds and accumulates to form clumps called Lewy bodies.
Braak maintained that abnormal alpha-synuclein may spread using the vagus nerve from the gut to the midbrain.
Dr. Pasricha said that he and other researchers have completed studies, such as this one from 2019, which found that “the pathological molecule that is associated with [Parkinson’s] can indeed travel from the gut to the brain.”
The researchers decided to use the TriNetX, a federated health research network, “to test this hypothesis in another way,” Dr. Pasricha said.
Should individuals with digestive issues worry?
Dr. Pasricha stressed to MNT that individuals with these four gut troubles should not blow the study’s results out of proportion.
“There is no need for alarm,” he said.
“The overall risk for developing [Parkinson’s disease] is low, so even a 2–4 increase still translates to a very low absolute risk. The overwhelming majority of patients with these [gastrointestinal] conditions will never develop [Parkinson’s disease].”
Therapies focusing on gut health could slow disease progression
Dr. Pasricha pointed out that the study has a key limitation. “A weakness is that [it]relies on physician-coded diagnoses which cannot be independently verified,” he said.
Dr. Dawson noted, “You don’t know what wasn’t recorded right now — some of the associations may be false.” However, he added that “it’s such a large study, and I think that the risk of that is small.”
Dr. Pasricha maintained the study has a lot going for it. “Its strength lies in the large number of patients, its design that incorporated two different analyses that were supportive of each other, and most importantly, including other neurological disorders as controls so as to better establish the specificity of these findings for [Parkinson’s disease] itself,” he said.
Dr. Dawson speculated that this study could lead to future therapies that could help slow the progression of Parkinson’s disease.
“The next major step forward would be what is going [on] in the gastrointestinal tract that predisposes one to develop Parkinson’s disease and is that mechanism something that can be treated?”
While it seems like there is considerable evidence of a link between the gut and the development of Parkinson’s disease, Dr. Dawson maintained that is important to look at the idea from every angle.
“You just keep building evidence,” he said. “And this is one more I think really strong piece of evidence to support the role of the gastrointestinal tract in Parkinson’s disease.”
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