Parkinson’s disease, a progressive neurodegenerative disorder, affects an estimated 8.5 million people worldwide — a figure that has more than doubled over the past three decades. A new study adds to a growing body of evidence that Parkinson’s disease, long believed to have its origins in the brain, may begin in the gut.
According to a study led by researchers at Harvard- affiliated Beth Israel Deaconess Medical Centre, the risk of developing Parkinson’s disease was 76 percent higher among those with damage to the lining of their upper gastrointestinal tract than among those without. The study sheds light on the way Parkinson’s may develop and suggests that increased vigilance among those with upper GI mucosal damage may be warranted. Damage is typically identified as ulcerations caused by the H. pylori bacterium, gastroesophageal reflux disease (GERD) and/or use of non-steroidal anti-inflammatory drugs (NSAIDS) such as Ibuprofen. The findings are published in JAMA Network Open.
Gastrointestinal problems are common in patients with neurodegenerative disorders, to the point where a condition known as “institutional colon” was once thought to afflict those who lived in mental health institutions. In Parkinson’s disease, the entire gastrointestinal tract is affected, causing complications such as constipation, drooling, trouble swallowing and delayed emptying of the stomach. These symptoms often appear up to two decades before motor symptoms such as rigidity or tremor.
Gut-First Pathway of Parkinson’s
People have, for the longest time, described Parkinson’s disease as a top-down disease — so, it starts in the brain and then percolates down to the gut, and that’s why patients have issues with their gastrointestinal tract. But another hypothesis suggests that, in many patients, it may be a bottom-up approach, where it starts in the gut and goes all the way up to the brain.
The study’s corresponding author Dr. Trisha S. Pasricha, a neuro-gastroenterologist and director of Clinical Research at the Institute for Gut-Brain Research at BIDMC said that a growing body of evidence suggests that Parkinson’s disease originates in the gut before affecting the central nervous system. She said people often think about the ways the brain influences the gut, but the gut can exert enormous influence on the brain in ways we are still only beginning to understand.
Many people who get Parkinson’s disease experience GI symptoms like constipation and nausea for years — even decades — prior to developing motor symptoms like difficulty walking or tremors. Dr. Trisha says they have been trying to better illuminate this ‘gut-first’ pathway of Parkinson’s disease because it can open new avenues for early intervention and treatment strategies.
A Retrospective Cohort Study
To explore the “gut-first hypothesis, the researchers performed a retrospective cohort study using patient data from an electronic database encompassing a representation of urban academic centers as well as outpatient clinics and community hospitals in the Greater Boston area. The analysis involved 9,350 patients with no history of Parkinson’s and who had had an upper endoscopy with biopsy between 2000 and 2005. An upper endoscopy is a procedure to image and diagnose problems in the esophagus, stomach, and first portion of the small intestine, which together make up the upper GI tract. Most patients were between the ages of 50 and 64 at the time of the procedure.
Patients with injuries to the lining of the upper GI tract, called mucosal damage, were matched in a 1:3 ratio with patients without mucosal damage. All patients were followed through July 2023. Of 2,338 patients with mucosal damage, 2.2 percent were later diagnosed with Parkinson’s disease, while of the 8,955 patients without mucosal damage, 0.5 percent went on to develop Parkinson’s.
After adjusting for confounders, the risk of developing Parkinson’s disease was 76 percent higher among those with a history of mucosal damage than among those without. On average, Parkinson’s disease was diagnosed 14.2 years after mucosal damage was detected on an upper endoscopy.
Rise in Number of Parkinson’s Cases
Globally, the number of people with Parkinson’s disease has doubled in the past 25 years, with some experts referring to this exponential surge as a “Parkinson pandemic.” Parkinson’s is the fastest growing neurological disorder worldwide, even surpassing Alzheimer’s disease, according to the Global Burden of Disease study, which pooled health outcomes data from 195 countries.
Much of the increase is because of an aging population, but the rise in incidence persists after adjusting for age-related factors. Only about 10 percent of cases can be traced to genetics, with the vast majority labelled as “sporadic” — without a known cause. Solving the mystery of why some people develop Parkinson’s and others don’t could lead to options for early detection, treatment and hopefully, one day, prevention.
A Reason for Caution Not Panic
The findings of this study have important implications for the early detection and treatment of Parkinson’s disease. By identifying individuals at risk based on gastrointestinal symptoms, doctors may be able to intervene earlier and potentially delay or prevent the onset of motor symptoms.
However, study author Subhash Kulkarni, an assistant professor at Beth Israel Deaconess Medical Center, says there is reason for caution, but there is no reason for panic as researcher are not saying that every person who has mucosal damage is going to develop Parkinson’s. There is an association and increased risk, and it has to be figured out what are the mechanisms by which the risk in these patient populations can be decreased.
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