Summary: People with a history of upper gastrointestinal (GI) damage have a 76% higher risk of developing Parkinson’s disease. The research highlights how conditions like GERD, peptic ulcers, and NSAID use may increase the risk of this neurodegenerative disorder.
The findings suggest that heightened monitoring for Parkinson’s symptoms in individuals with upper GI damage may be necessary. This study supports the “gut-first” hypothesis, proposing that Parkinson’s may originate in the gut before affecting the brain.
Key Facts:
- Upper GI damage increases Parkinson’s disease risk by 76%.
- Conditions like GERD, ulcers, and NSAID use are linked to this higher risk.
- Parkinson’s may originate in the gut before it impacts the central nervous system.
Source: BIDMC
A study led by researchers at Beth Israel Deaconess Medical Center (BIDMC) found the risk of developing Parkinson’s disease was 76% higher among those with a history of damage to the lining of their upper gastrointestinal (GI) tract than among those without.
The study sheds light on the way Parkinson’s may develop in some people and also suggests that increased vigilance among those with a history damage to the upper GI tract—typically ulcerations caused by the H. pylori bacterium, gastroesophageal reflux disease (GERD) and/or use of non-steroidal anti-inflammatory drugs (NSAIDS) such ibuprofen—for future Parkinson’s disease risk may be warranted.
The findings are published in JAMA Network Open. Co-authors included Jocelyn J. Chang of Tufts University School of Medicine; Subash Kulkarni of BIDMC.
“A growing body of evidence suggests that, at least in a subset of individuals, Parkinson’s disease originates in the gut before affecting the central nervous system,” said corresponding author Trisha S. Pasricha, MD, MPH, a neurogastroenterologist and director of Clinical Research at the Institute for Gut-Brain Research at BIDMC.
“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.
“Our lab has 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.”
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.
To explore this “gut-first hypothesis,” Pasricha and colleagues 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.
Investigators identified a cohort of patients with no history of Parkinson’s disease who underwent an upper endoscopy (EGD)—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—between the year 2000 and 2005.
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 of 2023.
Of 2,338 patients with mucosal damage, 2.2% were later diagnosed with Parkinson’s disease, while of the 8,955 patients without mucosal damage, 0.5% went on to develop Parkinson’s.
After adjusting for confounders, the risk of developing Parkinson’s disease was 76% 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.
“We found that a history of upper GI mucosal damage was associated with a 76% greater risk of subsequently developing Parkinson’s disease, highlighting the necessity for heightened monitoring of these patients,” said Pasricha, who is also an instructor of medicine at Harvard Medical School.
“NSAID use is so widespread—from back pain to headaches—and with peptic ulcers globally affecting upwards of 8 million people, understanding the path from mucosal damage to Parkinson’s disease pathology may prove crucial to early recognition of risk as well as potential intervention.”
About this Parkinson’s disease research news
Author: Jacqueline Mitchell
Source: BIDMC
Contact: Jacqueline Mitchell – BIDMC
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Upper Gastrointestinal Mucosal Damage and Subsequent Risk of Parkinson Disease” by Jocelyn J. Chang et al. JAMA Network Open
Abstract
Upper Gastrointestinal Mucosal Damage and Subsequent Risk of Parkinson Disease
Importance
The gut-first hypothesis of Parkinson disease (PD) has gained traction, yet potential inciting events triggering Parkinson pathology from gut-related factors remain unclear. While Helicobacter pylori infection is linked to mucosal damage (MD) and PD, it is unknown how upper gastrointestinal MD from any source increases PD risk.
Objective
To evaluate any association between upper endoscopy findings of MD and subsequent clinical PD diagnosis.
Design, Setting, and Participants
This was a retrospective cohort study of patients with no PD history undergoing upper endoscopy with biopsy between January 2000 and December 2005, with final follow-up assessments completed July 31, 2023. The study was conducted within the Mass General Brigham system, a multicenter network in the greater Boston, Massachusetts, area. Patients with MD were matched 1:3 to patients without MD based on age, sex, and date of initial endoscopy.
Exposure
MD, defined as erosions, esophagitis, ulcers, or peptic injury, observed on upper endoscopy or pathology reports.
Main Outcomes and Measures
The relative risk of PD given a history of MD, estimated using incident rate ratio (IRR) and multivariate Cox proportional hazard ratios (HRs).
Results
Of 9350 patients, participants had a mean (SD) age of 52.3 (20.3) years; 5177 (55.4%) were male; and 269 (2.9%) were Asian, 737 (7.9%) Black, and 6888 (73.7%) White. Most participants underwent endoscopy between the ages of 50 and 64 years (2842 [30.4%]).
At baseline, patients with MD were more likely to have a history of H pylori infection, proton-pump inhibitor use, chronic nonsteroidal anti-inflammatory drug use, gastroesophageal reflux disease, smoking, constipation, and dysphagia.
The mean (SD) follow-up time was 14.9 (6.9) years for the whole cohort, during which patients with MD were more likely to develop PD (IRR, 4.15; 95% CI, 2.89-5.97; P < .001) than those without MD, even after covariate adjustment (HR, 1.76; 95% CI 1.11-2.51; P = .01). Constipation, dysphagia, older age, and higher Charlson-Deyo Comorbidity Index were also associated with higher PD risk.
Conclusions and Relevance
In this cohort study, a history of upper gastrointestinal MD was associated with elevated risk of developing a clinical PD diagnosis. Increased vigilance among patients with MD for future PD risk may be warranted.
