Clinical Summary | Neurology | Neuro-degenerative Disorders
Upper gastrointestinal mucosal damage and subsequent risk of Parkinson's disease
Time to read: 03 minutes,48 seconds
Time to listen:06 minutes,43 seconds
Originally Published: 5 September 2024
Source: JAMA Network Open
Type of article: Clinical Research Summary
MedED Catalogue Reference: MNCS001
Category: Neurology
Cross-reference: Gerontology, Gastroenterology
Keywords: Parkinson's disease, gut health, neurodegenerative disorders, gastrointestinal mucosal damage (MD)
Originally Published: JAMA Network Open, 5 September 2024. This is a summary of the clinical study, reproduced under Creative Commons Attribution BY and in no way represents the original research. Links to all original material can be found at the end of this summary.
Key Take Aways
1. This study found that a history of upper gastrointestinal mucosal damage (MD) was associated with an increased risk of subsequently developing Parkinson's disease
2. Data suggest that the association between gastrointestinal mucosal damage and the risk of developing Parkinson's disease may not be contingent on one isolated abnormality but rather a cumulative effect of multiple GI inflammatory insults
3. The presence of H. pylori in biopsies significantly increased the likelihood of Parkinson's disease in patients with gastric mucosal damage, but not in those without, suggesting that H. pylori may enhance PD risk specifically in the context of mucosal damage
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Overview | Study Purpose | Study Design | Findings | Limitations | Conclusion | Original Research | Funding |
Overview
Parkinson's disease (PD) impacts approximately 8.5 million individuals globally, with its prevalence more than doubling over the past 30 years.
The disease is characterized by the degeneration of dopaminergic neurons in the substantia nigra, leading to both motor symptoms, such as tremors and rigidity, and nonmotor symptoms, including gastrointestinal issues. Emerging research suggests a potential "gut-first" hypothesis for PD, where pathology may begin in the gut and progress to the brain via the vagus nerve. However, the exact trigger for this process remains unclear.
Helicobacter pylori infection, linked to upper gastrointestinal issues, has garnered attention due to its higher prevalence in PD patients compared to the general population, suggesting a possible association. However, significant gaps persist in understanding the relationship between broader gastrointestinal mucosal damage (MD) and PD development. The role of nonsteroidal anti-inflammatory drugs (NSAIDs) remains ambiguous, as while some studies indicate potential neuroprotective effects, others do not find a clear connection to PD risk.
The researchers of this study, Chang et al. hypothesised that notable mucosal defects, including those related to H. pylori and NSAID use, could be linked to the later development of PD.
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Study Purpose
This study's purpose was to evaluate whether there was any association between upper endoscopy findings of gastrointestinal mucosal damage and subsequent clinical Parkinson's diagnosis.
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Study Design & Selection Criteria
Patients with MD were matched 1:3 to patients without MD based on age, sex, and date of initial endoscopy to obtain a final cohort of 9350 patients.
Each participant was followed up until either 1) a diagnosis of PD or 2) the patient died, or 3), in the absence of a PD diagnosis, censoring either at an outpatient visit with no subsequent follow-up for over two years, indicating loss to follow-up, or the final follow-up assessment date.
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Findings
Of the 9,350 patients, more than half were male (55.4%), and the mean age was 52.3 years.
The majority of the patients who underwent endoscopy were between 50 and 64 years. Of these, 2,337 patients were found to have mucosal damage during endoscopy.
Parkinson’s Disease and Mucosal Damage
The overall incidence of PD in the cohort was consistent with global figures, and survival analysis showed a shorter time to PD diagnosis for those with MD.
Risk Factors
Factors that increased the likelihood of developing PD included older age, higher Charlson Comorbidity Index (CCI), constipation, and dysphagia.
Asian, Black, and other races had a lower risk of PD, while gender and a history of H. pylori infection did not influence PD risk.
Subgroup Analyses
In the subgroup of patients with MD, a higher prevalence of chronic NSAID use and GERD was found among those who developed PD. In this group, H. pylori infection and GERD were associated with an increased PD risk.
In patients without MD, GERD was the only factor more prevalent among those who later developed PD, but no other covariates were linked to PD risk.
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Limitations
The study has some limitations, including the inability to track Parkinson’s disease (PD) cases diagnosed outside their healthcare system, which may affect the results. There may also be a bias toward diagnosing PD in patients already receiving treatment for movement disorders.
Although efforts were made to account for age and comorbidity differences, using diagnostic codes may still lead to inaccuracies. Furthermore, the small sample sizes in the case-control analyses suggest that more research is needed to confirm these findings and address potential unknown biases.
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Conclusion
In this cohort study of 9350 patients with no prior history of PD, the researchers determined that mucosal damage on upper endoscopy was associated with a 76% greater risk of developing a clinical PD diagnosis. The findings underscore the need for increased monitoring of patients with MD due to their vulnerability to PD and suggest the importance of establishing gut biomarkers for early detection.
Given the global prevalence of peptic ulcer disease (affecting over 8 million people) and widespread H. pylori infections, timely detection and management of H. pylori, along with MD, may be critical for early identification and intervention against PD.
Access the original research
Chang, J. J., Kulkarni, S., & Pasricha, T. S. (2024). Upper Gastrointestinal Mucosal Damage and Subsequent Risk of Parkinson Disease. JAMA network open, 7(9), e2431949. https://doi.org/10.1001/jamanetworkopen.2024.31949
Reproduced under Creative Commons CC-BY License
Conflict of Interest, Funding and Support
Role of the Funder/Sponsor
The study's funder had no role in the design, data collection, data analysis, data interpretation, or writing of the report.
Conflict of Interest Disclosures
Dr Pasricha reported receiving grants from the American Gastroenterological Association during the conduct of the study. No other disclosures were reported.
Funding/Support
Dr Kulkarni is supported by grants from the National Institute on Aging (R01AG066768 and R21AG072107).
Dr Pasricha is funded by the American Gastroenterological Association Research Foundation’s Research Scholar Award (AGA2022-13-03).
This work was conducted with support from the UM1TR004408 award through Harvard Catalyst: The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) and financial contributions from Harvard University and its affiliated academic healthcare centers.
This study was reproduced under Creative Commons CC-BY licence.
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