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Gastrointestinal (GI) mucosal damage seen on upper endoscopy was tied to a 76% higher risk of a subsequent Parkinson's disease diagnosis, a retrospective cohort study showed.

Over an average follow-up of nearly 15 years, people with upper GI mucosal damage were more likely than those without it to develop Parkinson's disease (HR 1.76, 95% CI 1.11-2.51, P=0.01), reported Trisha Pasricha, MD, MPH, of Beth Israel Deaconess Medical Center in Boston, and co-authors in .

Mucosal damage was defined as erosions, esophagitis, ulcers, or peptic injury on esophagogastroduodenoscopy (EGD) or pathology reports.

At baseline, patients with mucosal damage were more likely to have a history of Helicobacter pylori infection, proton-pump inhibitor use, chronic nonsteroidal anti-inflammatory drug use, gastroesophageal reflux disease, smoking, constipation, and dysphagia, the researchers said.

The study is one of several linking Parkinson's disease with earlier systemic or gut inflammation.

"There has been a growing body of literature supporting the idea that, at least for some patients, Parkinson's disease may originate in the gut," Pasricha told 番茄社区.

"We know that many patients with Parkinson's disease experience symptoms like constipation or trouble swallowing years, or even decades, before they get motor symptoms. And studies have found alpha-synuclein deposition throughout the gastrointestinal tract," she said.

Anecdotal evidence seemed to suggest a higher correlation between peptic ulcers and Parkinson's disease, Pasricha pointed out. "Here, we showed for the first time that a history of upper gastrointestinal mucosal damage, which we confirmed by looking at endoscopic and pathology reports, was associated with a 76% greater risk of developing Parkinson's disease," she noted.

"To emphasize, this is a study of association, not causation, which is part of what makes these results so intriguing," Pasricha observed.

"Dopamine plays an important role in gastrointestinal mucosal integrity," she said. "So, is mucosal damage the trigger that leads to pathologic alpha-synuclein misfolding, or do people destined to develop Parkinson's have subclinical decreases in dopamine increasing their risk of mucosal damage well in advance of motor symptoms? Those are the kinds of questions we're working on next."

What causes Parkinson's disease is unclear. An idea first developed about 20 years ago is the , which proposes that in a subset of patients, alpha-synuclein pathology originates in the gut and travels to the brain through the vagus nerve. Since then, many involved in Parkinson's development or progression have been studied.

In this analysis, Pasricha and colleagues studied 9,350 patients in the Mass General Brigham system with no Parkinson's history who had an upper endoscopy with biopsy between January 2000 and December 2005, following these patients through July 2023. They matched patients with mucosal damage 1:3 to patients without mucosal damage based on age, sex, and date of initial endoscopy.

Participants had a mean age of about 52. More than half (55.4%) were men; most were white (73.7%), 7.9% were Black, and 2.9% were Asian.

Over a mean follow-up of 14.9 years, Parkinson's diagnoses emerged for 52 patients (2.2%) with upper GI mucosal damage and 48 patients (0.5%) without mucosal damage (incident rate ratio 4.15, 95% CI 2.89-5.97, P<0.001).

Mean age at Parkinson's diagnosis was 73. Factors associated with an increased risk of developing Parkinson's included age, Charlson-Deyo Comorbidity Index score, constipation, and dysphagia. Asian or Black race was associated with a decreased risk of developing Parkinson's.

Overall, sex and history of H. pylori infection on EGD were not associated with Parkinson's risk. Subgroup analyses showed the initial presence of H. pylori on biopsies was associated with an increased probability of Parkinson's in people who had mucosal damage, but not in those without mucosal damage.

The study had several limitations, Pasricha and co-authors acknowledged. Parkinson's cases that were diagnosed and treated outside the Mass General Brigham system were not included, nor were outside reports of mucosal damage.

"This presents a risk of a carry-over effect if, for example, a diagnosis of Parkinson's disease was made before the patient entered our cohort but was not mentioned until after experiencing mucosal damage," the researchers wrote. "We believe that this may be mitigated by our efforts to confirm a diagnosis of Parkinson's disease through assessing prescription information."

Surveillance bias toward patients with mucosal damage was a possibility, and unknown variables may have influenced results.

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