A recent retrospective cohort study has found a significant association between upper gastrointestinal (GI) mucosal damage and an increased risk of developing Parkinson’s disease. According to the study, individuals with upper GI mucosal damage, as identified through upper endoscopy, had a 76% higher risk of being diagnosed with Parkinson’s disease compared to those without such damage.
Over an average follow-up period of nearly 15 years, those with GI mucosal damage had a higher likelihood of developing Parkinson’s disease (HR 1.76, 95% CI 1.11-2.51, P=0.01), as reported by Trisha Pasricha, MD, MPH, from Beth Israel Deaconess Medical Center in Boston, and colleagues in JAMA Network Open.
Mucosal damage in this context includes erosions, esophagitis, ulcers, or peptic injury as noted in esophagogastroduodenoscopy (EGD) or pathology reports. At baseline, patients with mucosal damage were more frequently reported to have a history of Helicobacter pylori infection, use of proton-pump inhibitors, chronic use of nonsteroidal anti-inflammatory drugs, gastroesophageal reflux disease, smoking, constipation, and dysphagia.
As reported by medpagetoday.com, this study adds to a growing body of research suggesting a connection between Parkinson’s disease and early systemic or gastrointestinal inflammation. “There is increasing evidence that, for some patients, Parkinson’s disease might originate in the gut,” Pasricha explained. Symptoms such as constipation or difficulty swallowing often appear years before motor symptoms, and research has shown alpha-synuclein deposits throughout the gastrointestinal tract.
This study, which links upper GI mucosal damage to Parkinson’s disease risk, is notable for its novel findings. “We have shown for the first time that a history of upper GI mucosal damage is associated with a 76% increased risk of Parkinson’s disease,” Pasricha said. However, she emphasized that this study establishes an association rather than causation.
The underlying mechanisms remain unclear. Pasricha speculates that dopamine, which is crucial for gastrointestinal mucosal health, may play a role. “Is mucosal damage a trigger for pathological alpha-synuclein misfolding, or do individuals predisposed to Parkinson’s have reduced dopamine levels that increase their risk of mucosal damage?” she asked.
This study involved 9,350 patients from the Mass General Brigham system who had an upper endoscopy with biopsy between January 2000 and December 2005. The researchers followed these patients until July 2023, comparing those with mucosal damage to those without, matched by age, sex, and date of initial endoscopy.
The mean age of participants was approximately 52, with 55.4% being male and the majority being white. Parkinson’s disease was diagnosed in 2.2% of patients with GI mucosal damage compared to 0.5% of those without (incident rate ratio 4.15, 95% CI 2.89-5.97, P<0.001).
The study identified several factors associated with an increased risk of Parkinson’s, including age, Charlson-Deyo Comorbidity Index score, constipation, and dysphagia. Race was a factor in risk reduction, with Asian or Black patients showing a decreased risk.
The researchers acknowledged limitations, including the exclusion of Parkinson’s cases diagnosed outside the Mass General Brigham system and potential surveillance bias. However, they believe their rigorous approach to confirming diagnoses through prescription data helps mitigate these concerns.