Parkinson’s may begin in the gut, study says, adding to growing evidence

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Researchers found that people with upper gastrointestinal conditions were far more likely to develop Parkinson’s disease later in life

 

Upper Gastrointestinal Mucosal Damage and Subsequent Risk of Parkinson Disease (2024)
Jocelyn J. Chang; Subhash Kulkarni; Trisha S. Pasricha

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. WhileHelicobacter pyloriinfection is linked to mucosal damage (MD) and PD, it is unknown how upper gastrointestinal MD from any source increases PD risk.

OBJECTIVES
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.

EXPOSURES
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.

KEY POINTS
Question Is upper gastrointestinal mucosal damage associated with increased risk of subsequent Parkinson disease (PD) diagnosis?

Findings In this cohort study of 9350 patients with no prior history of PD, findings of mucosal damage on upper endoscopy were associated with a 76% greater risk of developing a clinical PD diagnosis.

Meaning These findings suggest that increased vigilance among patients with upper gastrointestinal mucosal damage for future PD risk may be warranted.


Link | PDF (JAMA Network Open) [Open Access]

 

The study is about upper GIT mucosal damage, but I wouldn't be surprised if that damage results in changes in the microbiome further down the GIT which in turn affect the brain chemistry. Alternatively, it could be the response of the enteric nervous system or vagus nerves, which might have more triggers than the ones studied.