Upper Gastrointestinal Mucosal Damage Increases Risk for Parkinson Disease

Patients with a history of upper gastrointestinal (GI) mucosal damage have an increased risk of developing Parkinson disease (PD), according to study findings published in JAMA Network Open.

Researchers conducted a retrospective cohort study and 2 nested case-control studies to assess the relationship between upper endoscopy findings of mucosal damage and subsequent diagnosis of PD. Patients within the Mass General Brigham system who had a history of upper endoscopy with biopsy between 2000 and 2005, but no history of PD prior to initial upper endoscopy were eligible for inclusion. Patients with positive findings for mucosal damage were matched 1:3 with patients without mucosal damage, which was defined as the presence of erosion, esophagitis, ulcer, or peptic injury. Incident rate ratios (IRRs) and multivariate Cox proportional hazard ratios (HRs) were used to estimate the relative risk for PD given a history of mucosal damage. 

A total of 9350 patients (mean age at endoscopy, 52.3; men, 55.4%; White, 73.7%) were included in the analysis, of whom 2337 had mucosal damage and 7013 did not.

Among the 2338 patients with mucosal damage, 52 (2.2%) were ultimately diagnosed with PD. Of the 8955 patients without mucosal damage, 48 (0.5%) were later diagnosed with PD. Patients with vs without mucosal damage demonstrated a higher risk of developing PD (IRR, 4.15; 95% CI, 2.89-5.97; P <.001). After adjusting for covariates, the risk for PD associated with mucosal damage remained significant (HR, 1.76; 95% CI, 1.11-2.51; P =.01).

Overall, mean lead-time between detection of mucosal damage and PD diagnosis was 14.2 years and mean age at diagnosis was 72.7.

Factors associated with an increased PD risk included:

• Age (HR, 1.04; 95% CI, 1.02-1.05; P <.001);
• Charlson-Deyo Comorbidity Index (HR, 1.21; 95% CI, 1.09-1.35; P <.001);
• Constipation (HR, 2.65; 95% CI, 1.72-4.08; P <.001); and,
• Dysphagia (HR, 2.33; 95% CI, 1.52-3.56; P <.001).

Asian, Black, and other race were associated with a decreased risk for PD (HR, 0.70; 95% CI, 0.54-0.89; P =.004), while sex and Helicobacter pylori infection on endoscopy were not associated with PD risk.

In the first nested subgroup of patients with mucosal damage, the presence of H pylori on initial biopsy (adjusted odds ratio [aOR], 3.84; 95% CI, 1.22-12.13; P =.02) and gastroesophageal reflux disease (GERD; aOR, 3.92; 95% CI, 1.04-14.76; P =.04) were both associated with a higher risk of developing a diagnosis of PD.

Within the second nested subgroup of patients without mucosal damage, however, no covariates were associated with an increased risk for PD.

Study limitations include the inability to account for cases of PD that were diagnosed and treated outside the MGB system, potential surveillance bias, reliance on diagnostic codes for exposures and outcomes, relatively small sample sizes, and risk for bias due to unknown confounding.

“These findings highlight the necessity for heightened monitoring of patients with MD [mucosal damage] given their increased clinical PD susceptibility and the importance of establishing gut biomarkers,” the researchers concluded.