胃肠道粘膜损伤与帕金森病的后续风险

Jocelyn J Chang, Subhash Kulkarni, Trisha S Pasricha
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摘要

导言:帕金森病(Parkinsons Disease,PD)的 "肠道第一 "假说已获得广泛关注,但肠道相关因素引发帕金森病的诱因仍不清楚。幽门螺杆菌感染与消化道损伤有关,在帕金森病患者中的发病率是幽门螺杆菌感染的1.47倍,但胃肠道粘膜损伤(MD)如何增加帕金森病的发病风险尚不清楚。我们的目的是研究上消化道内镜检查发现的 MD 与随后发生的消化道疾病之间的关联:在我们的回顾性研究中,18305 名成人在 2000 年至 2005 年间接受了上消化道内窥镜检查,但之前未患过腹泻症,我们将 MD 患者与非 MD 患者进行了配对。采用发病率比(IRR)和多变量考克斯分析法评估了MD患者与非MD患者的PD风险,并对协变量进行了控制:在配对队列中,MD 患者发生 PD 的几率明显更高(IRR 3.00,p<0.0001),即使经过协变量调整后也是如此(HR 2.42,p<0.001)。包括便秘、吞咽困难、年龄较大和男性在内的协变量也与较高的腹泻风险有关。在 MDs 中,幽门螺杆菌的存在(AOR 5.38,p=0.04)和长期使用非甾体抗炎药(AOR 3.28,p=0.04)增加了 PD 的几率,而长期吸烟降低了 PD 的几率(AOR 0.19,p<0.05):结论:MD会增加PD风险,而幽门螺杆菌仅在MD存在时才会增加风险,这表明PD与胃粘膜破坏之间存在更密切的联系。此外,长期使用非甾体抗炎药会显著提高MD患者患腹泻的几率,而长期吸烟则会降低这种情况下的腹泻风险。有必要提高MD患者对未来PD风险的警惕,同时需要进一步的研究来阐明确切的病理生理学。
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GASTROINTESTINAL MUCOSAL DAMAGE AND SUBSEQUENT RISK OF PARKINSONS DISEASE
Introduction: The gut-first hypothesis of Parkinsons 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. Methods: In 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. Results: In 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). Conclusion: MD 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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