People who have had their appendix removed are 3 times more likely to develop Parkinson’s disease than those who have not, according to a new retrospective study of more than 62 million individuals.
The investigation, to be presented on Monday, May 20, 2019, during Digestive Disease Week in San Diego, adds to a growing body of evidence demonstrating that gastrointestinal issues may be connected with the neurodegenerative disorder.
“Although some studies have shown that appendectomy may protect against Parkinson’s disease, we found a strong association between appendectomy and the development of Parkinson’s at least six months after the appendix is removed,” says senior study author Gregory Cooper, MD, a professor of medicine and population and quantitative health sciences at University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine in Ohio.
Dr. Cooper and his colleagues reviewed the electronic health records of more than 62 million people from 1997 to 2018, drawn from 26 major health systems. Researchers tout the investigation as the biggest on this topic to date, covering a population that is generalizable to the United States as a whole.
From this huge database, scientists identified 488,190 patients who had their appendix removed. Of these, 4,470 or 0.9 percent received a diagnosis of Parkinson’s disease at least six months after the surgery. Only 0.3 percent, or 177,230 of the remaining 61.7 million people included in the study developed the disorder. The investigators note that risk levels were similar across all age groups, regardless of gender or race.
Cooper stresses that the overall study population with Parkinson’s was relatively small.
“There was a threefold higher risk [of Parkinson’s disease], but in the grand scheme of things this was still a relatively low frequency.”
Protein in the Gut May Play a Role
Although study authors are uncertain as to why appendectomy may increase the risk of Parkinson’s, they suspect that a protein found in the gastrointestinal tract may be a factor.
The protein alpha-synuclein is a major structural component of Lewy bodies, abnormal accumulations of protein that develop inside nerve cells and contribute to Parkinson's. Depending on where it builds up in the brain, alpha-synuclein may produce constipation, depression, sleep disorders, tremors, slowness, or problems with thinking.
“This protein is also found in the gastrointestinal tract but the highest concentration is in the appendix,” says Cooper.
So why would removing a source of this potentially toxic protein be harmful?
Alessandro Di Rocco, MD, a neurology specialist and Northwell Health’s director of the Movement Disorders Program in Great Neck, New York, says, “There are speculations raised by the study that during the removal of the appendix, clumps of abnormal alpha-syncuclein may be released, and that these clumps could then spread and colonize the brain, eventually inducing Parkinson's disease.”
Another possibility may be that the appendix modifies the immune response to alpha-synuclein, and over time this change in immune response may lead to the harmful accumulation, according Dr. Di Rocco, who was not involved in the study.
He says that more research is needed to determine how alpha-synuclein may be used as biomarker to identify those at risk of Parkinson's and possibly chart the progression of the disease.
Digestive Tract Health Is Vital to Well-Being
No matter what factors may be at play, this investigation provides more evidence that gastrointestinal health may be connected to Parkinson’s. A prior study, published in August 2018 in the journal JAMA Neurology, revealed that patients with inflammatory bowel disease were 28 percent more likely to get Parkinson’s compared with those without IBD.
Because of this association, researchers have been working on therapies to stop alpha-synuclein proteins traveling from the digestive system to the brain.
Although this study drew on a large database, Cooper and his team would like to gather more information from a limited group of patients.
“A smaller sample population with more detailed medical records might help tease out some confounding factors and more information on family history,” he says.
The data also did not provide the actual time interval from the appendectomy to the diagnosis of Parkinson’s.
“We were able to identify those who developed Parkinson’s at least six months after the operation, but we don’t know if a patient had an appendectomy two years prior to Parkinson’s diagnosis or 10 years prior, so that’s a limitation,” says Cooper.
Study authors underscore that the outcomes do not demonstrate that appendectomy causes Parkinson’s.
“The results are still incomplete and somewhat contradictory, so they cannot be used to make specific recommendations,” says Di Rocco. “I certainly would not recommend to anyone who needs an appendectomy to avoid the procedure because it may increase the risk of developing Parkinson's disease.”
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