Upper and Lower Gastrointestinal Symptom Association and Duration Preceding Parkinson’s Disease

Gadi, Sanjay R.V.; Chang, Jocelyn; Videnović, Aleksandar; Kuo, Braden; Pasricha, Trisha S.

doi:10.1016/j.gastha.2022.12.005

Cited by 4 publications

(9 citation statements)

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“…Our other findings are consistent with existing literature, which identifies age, sex, constipation, and dysphagia as risk factors for PD, thereby demonstrating the reproducibility of our results 3 . Conversely, our study discerns no significant link between esophagitis and PD in patients with MD, suggesting that the relationship between MD and PD risk may be contingent upon either a cumulative effect of various forms of GI inflammation or a synergistic impact of multiple manifestations of MD.…”

Section: Discussionsupporting

confidence: 93%

Gastrointestinal Mucosal Damage and Subsequent Risk of Parkinson’s Disease

Chang,

Kulkarni,

Pasricha

2024

Preprint

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IntroductionThe 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.MethodsIn 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.ResultsIn 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).ConclusionMD 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.

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Section: Discussionsupporting

confidence: 93%

Gastrointestinal Mucosal Damage and Subsequent Risk of Parkinson’s Disease

Chang,

Kulkarni,

Pasricha

2024

Preprint

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“…The first step in the evaluation and treatment of DES is to assess the degree of underlying reflux as approximately one-third of patients with DES in the general population have pathologic acid exposure 34 . The prevalence of reflux among patients with DES PD has not been studied; however, patients with PD have nearly twice the odds of experiencing heartburn symptoms compared to the general population, 5 and spastic disorders of the esophagus like DES may be a reactive clearance mechanism in response to reflux as well as to peptic strictures 35 . In these patients, we therefore first recommend a trial of proton pump inhibition with possible additional diagnostics including ambulatory pH monitoring (off acid suppression) as well as the evaluation on upper endoscopy for a possible stricture with consideration of empiric dilation.…”

Section: Esophageal Dysphagiamentioning

confidence: 99%

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confidence: 99%

“…Time from gastrointestinal symptoms to Parkinson’s disease diagnosis. Figure reproduced with permission 5 . GI indicates gastrointestinal.…”

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confidence: 99%

“…2). 5 Because of newer evidence in this regard, constipation was recently added to the diagnostic criteria for prodromal PD by the Movement Disorder Society Task Force on the Definition of Parkinson's Disease. 6 The earlier onset of GI symptoms underscores the proposed pathophysiological gut-brain pathway of PD, popularized by Braak's hypothesis.…”

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confidence: 99%

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Management of Gastrointestinal Symptoms in Parkinson’s Disease

Pasricha,

Guerrero-Lopez,

Kuo

2024

Journal of Clinical Gastroenterology

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Gastrointestinal symptoms in Parkinson’s disease (PD) are among the most prevalent and debilitating of complications and present unique diagnostic and management challenges. Patients with PD commonly experience dysphagia, nausea, bloating, and constipation related to pathologic involvement of the enteric nervous system. In turn, gastrointestinal complications may impact motor fluctuations and the efficacy of levodopa therapy. This review will explore the common gastrointestinal manifestations of PD with an emphasis on clinical presentation, workup, and treatment strategies.

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Upper Gastrointestinal Mucosal Damage and Subsequent Risk of Parkinson Disease

Chang,

Kulkarni,

Pasricha

2024

JAMA Netw Open

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ImportanceThe gut-first hypothesis of Parkinson disease (PD) has gained traction, yet potential inciting events triggering Parkinson pathology from gut-related factors remain unclear. While Helicobacter pylori infection is linked to mucosal damage (MD) and PD, it is unknown how upper gastrointestinal MD from any source increases PD risk.ObjectiveTo evaluate any association between upper endoscopy findings of MD and subsequent clinical PD diagnosis.Design, Setting, and ParticipantsThis 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.ExposureMD, defined as erosions, esophagitis, ulcers, or peptic injury, observed on upper endoscopy or pathology reports.Main Outcomes and MeasuresThe relative risk of PD given a history of MD, estimated using incident rate ratio (IRR) and multivariate Cox proportional hazard ratios (HRs).ResultsOf 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 &lt; .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 RelevanceIn 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.

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Upper and Lower Gastrointestinal Symptom Association and Duration Preceding Parkinson’s Disease

Cited by 4 publications

References 9 publications

Gastrointestinal Mucosal Damage and Subsequent Risk of Parkinson’s Disease

Gastrointestinal Mucosal Damage and Subsequent Risk of Parkinson’s Disease

Management of Gastrointestinal Symptoms in Parkinson’s Disease

Upper Gastrointestinal Mucosal Damage and Subsequent Risk of Parkinson Disease

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