Study warns of increased PD risk among people with upper GI mucosal damage history

A history of upper gastrointestinal (GI) mucosal damage, such as peptic ulcer disease and erosions, has been associated with subsequent incidence of Parkinson’s disease (PD) in a study.

In a large retrospective cohort, participants with upper GI mucosal damage had about 4 times the rate of having a later diagnosis of PD compared with those who did not have mucosal damage (2.2 percent vs 0.5 percent; incidence rate ratio [IRR], 4.15, 95 percent confidence interval [CI], 2.89–5.97; p<0.001). [JAMA Netw Open 2024;7:e2431949]

Mucosal damage remained significantly associated with subsequent PD incidence in an analysis adjusted for additional covariates such as age at endoscopy, sex, race, Charlson comorbidity index (CCI), constipation, dysphagia, and H. pylori (hazard ratio [HR], 1.76, 95 percent CI, 1.11–2.51; p=0.01). 

Risk factors for PD included age (HR, 1.04, 95 percent CI, 1.02–1.05; p<0.001), CCI (HR, 1.21, 95 percent CI, 1.09–1.35; p<0.001), constipation (HR, 2.65, 95 percent CI, 1.72–4.08; p<0.001), and dysphagia (HR, 2.33, 95 percent CI, 1.52–3.56; p<0.001). Conversely, Asian, Black, and other race were protective (HR, 0.70, 95 percent CI, 0.54–0.89; p=0.004). Sex and history of H. pylori infection were not associated with PD risk.

Among participants with mucosal damage, the presence of H. pylori on initial biopsy was associated with a markedly higher probability of having a subsequent diagnosis of PD (adjusted odds ratio [aOR], 3.84, 95 percent CI, 1.22–12.13; p=0.02), as was gastroesophageal reflux disease (GERD; aOR, 3.92, 95 percent CI, 1.04–14.76; p=0.04). Chronic smoking, chronic NSAID use, and proton pump inhibitor (PPI) use were not associated with PD risk.

Among participants without mucosal damage, on the other hand, none of the covariates were associated with the risk of PD.

“Overall … our data suggest that the association between mucosal damage and PD risk may not be contingent on one isolated abnormality but rather a cumulative effect of multiple GI inflammatory insults,” the investigators noted.

“The cumulative burden or the diversity of inflammation sites within the GI tract could be instrumental in PD risk elevation, possibly through a threshold effect on the gut-brain axis,” they added.

The investigators highlighted the need for heightened monitoring of patients with mucosal damage given their increased clinical PD susceptibility, as well as the importance of establishing gut biomarkers.

“With peptic ulcer disease globally affecting upwards of 8.09 million people and H. pylori infection even more widespread, timely detection and treatment of H. pylori infection, along with mucosal management, may prove crucial to early recognition of risk of and potentially intervention against PD,” they said. [BMC Gastroenterol 2022;22:58]

The study included 9,350 participants who underwent upper endoscopy with biopsy. The mean age at the time of endoscopy was 52.3 years, with most participants being male (55.4 percent) and White (73.7 percent). A total of 2,337 participants (25 percent) exhibited evidence of mucosal damage on endoscopy, and they were more likely to have a history of H. pylori infection, PPI use, chronic NSAID use, GERD, smoking, constipation, and dysphagia. The mean follow-up time was 14.9 years for the entire cohort.