Introduction The gut-first hypothesis of Parkinson’s Disease (PD) has gained traction, yet the inciting events triggering PD from gut-related factors remain unclear. While H. pylori infection is linked to peptic injury and is 1.47 times more prevalent in PD individuals, it is unknown how gastrointestinal mucosal damage (MD) may increase the risk of PD. We aimed to study the association between upper endoscopy findings of MD and subsequent PD development.

Methods In our retrospective study of 18,305 adults without prior PD, undergoing upper endoscopy between 2000 and 2005, patients with MD were matched with non-MDs. PD risk in MDs versus non-MDs was assessed using incidence rate ratio (IRR) and multivariate Cox analysis, controlling for covariates.

Results In the matched cohort, MD patients were significantly more likely to develop PD (IRR 3.00, p<0.0001), even after covariate adjustment (HR 2.42, p<0.001). Covariates including constipation, dysphagia, older age, and male sex were also associated with higher PD risk. Among MDs, H. pylori presence (AOR 5.38, p=0.04) and chronic NSAID use (AOR 3.28, p=0.04) increased PD odds, while chronic smoking decreased PD odds (AOR 0.19, p<0.05).

Conclusion MD elevates PD risk, with H. pylori increasing risk only in the presence of MD, suggesting a closer link between PD and gastric mucosa disruption. Furthermore, chronic NSAID use significantly raises PD odds in MD, while chronic smoking reduces PD risk in this context. Increased vigilance among MD patients for future PD risk is warranted, with further studies needed to elucidate precise pathophysiology.

The authors have declared no competing interest.

This study was funded by the American Gastroenterological Association Research Foundations Research Scholar Award AGA2022-13-03

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