Upper Gastrointestinal Mucosal Damage and Subsequent Risk of Parkinson Disease

Abstract

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.

Figure 1.. Study Flowchart

MD indicates mucosal damage; PD, Parkinson disease.

Figure 2.. Survival Curves for Time to Parkinson Disease Diagnosis

MD indicates mucosal damage.

Figure 3.. Association of Risk Factors With Parkinson Disease Diagnosis

Other race and ethnicity included Asian and Black individuals as well as those with racial identifications that did not fit into those categories. CCI indicates Charlson-Deyo Comorbidity Index; GERD, gastroesophageal reflux disease; H pylori, Helicobacter pylori; HR, hazard ratio; NSAID, nonsteroidal anti-inflammatory drug; OR, odds ratio; PPI, proton-pump inhibitor.