An analysis of the health system records of more than 62 million people in the United States has found a link between appendix removal and raised risk of developing Parkinson's disease.
The researchers compared data on people who had undergone an appendectomy, or appendix removal, to those who had not.
The analysis showed that those who had undergone an appendectomy were more than three times more likely to develop Parkinson's disease later on.
The findings are further evidence of a connection between the gut and the brain in Parkinson's disease.
Previous studies that have focused on the role of the appendix have drawn conflicting conclusions about whether having an appendectomy might raise or lower a person's risk of developing Parkinson's disease.
For example, a 2016 Movement Disorders study of about 1.5 million people in Denmark found that people who had had an appendectomy were at slightly higher risk of developing Parkinson's disease in the future.
In contrast, a 2018 Science Translational Medicine study of over 1.6 million people in Sweden tied appendix removal to a lower risk and delay in the development of Parkinson's disease.
This controversy spurred the new study investigators to embark on a much more extensive analysis that drew on the electronic health records of 62.2 million people in 26 health systems in the U.S.
In a Gastroenterology abstract about the study, the authors suggest that what is missing from the research on appendix removal and Parkinson's disease risk is "large-scale epidemiological data."
Lead study author Dr. Mohammed Z. Sheriff, who works as a physician at University Hospitals Cleveland Medical Center and Case Western Reserve University, also in Cleveland, OH, is presenting the findings at the 2019 Digestive Disease Week meeting that takes place May 18–21 in San Diego, CA.
Parkinson's, alpha-synuclein, and the gut
Parkinson's is a disease that gradually destroys cells in a part of the brain that helps control movement. The symptoms of Parkinson's include movement rigidity, tremor, slowness, and balance difficulties.
Because it most often strikes older people, the number and proportion of individuals living with Parkinson's disease are rising in aging populations. As yet, there is no cure and no treatment that slows down Parkinson's disease.
An avenue that scientists are pursuing concerns alpha-synuclein, which is a protein that features in the development of Parkinson's disease.
Although it is not clear what function it serves in those without the disease, alpha-synuclein forms toxic clumps called Lewy bodies in the brains of people with Parkinson's disease.
Dr. Sheriff says that more recent research has found clumps of alpha-synuclein in the digestive tract of people in the early stages of Parkinson's disease.
"This is why," he explains, "scientists around the world have been looking into the gastrointestinal tract, including the appendix, for evidence about the development of Parkinson's."
Appendectomy and higher Parkinson's risk
Of the 62.2 million patient records that they analyzed, the team identified 488,190 people who had undergone an appendectomy. Of these, 4,470 individuals (0.92%) went on to receive a diagnosis of Parkinson's disease.
Of the remaining 61.7 million people, only 177,230 individuals (0.29%) received a Parkinson's disease diagnosis.
The team also found that the more than three times higher likelihood of developing Parkinson's disease following an appendectomy was not dependent on age, sex, or race.
"This research shows a clear relationship between the appendix, or appendix removal, and Parkinson's disease, but it is only an association. Additional research is needed to confirm this connection and to better understand the mechanisms involved."
Dr. Mohammed Z. Sheriff