Institute of Psychiatry, Psychology & Neuroscience, Department of Neurosciences, King's College London, London, United Kingdom.
Parkinson's Foundation Centre of Excellence, King's College Hospital, London, United Kingdom.
J Parkinsons Dis. 2021;11(3):1209-1219. doi: 10.3233/JPD-212570.
Constipation is regarded as one of the prodromal features of Parkinson's disease (PD) and there is emerging evidence linking gastrointestinal dysfunction and cognitive impairment (CI) in PD.
We explored whether constipation is associated with development of CI in two independent cohorts of de novo PD patients (n = 196 from the Non-motor International Longitudinal Study [NILS] and n = 423 from the Parkinson's Progression Markers Initiative [PPMI] study).
Constipation was clinically defined using the Non-Motor Symptoms Scale (NMSS) item-21 [NILS] and Scales for Outcomes in PD-Autonomic (SCOPA-AUT) item-5 [PPMI]. We assessed baseline group differences (PD with or without constipation) in CI, global non-motor symptoms burden, motor dysfunction, and striatal dopaminergic denervation. Kaplan-Meier method estimated group differences in cumulative proportion of patients with incident CI over three years. In PPMI, we subsequently performed univariate and multivariate Cox survival analyses to evaluate whether constipation predicts incident mild cognitive impairment or dementia over a 6-year period, including constipation and other known predictors of CI as covariates.
Patients with constipation had greater motor and global non-motor burden in both cohorts at baseline (p < 0.05). Kaplan-Meier plots showed faster conversion to CI in patients with constipation in both cohorts (p < 0.05). In PPMI, 37 subjects developed dementia during a mean follow-up of 4.9 years, and constipation was an independent predictor of dementia onset (hazard ratio = 2.311; p = 0.02).
Constipation in de novo PD patients is associated with development of cognitive decline and may serve as a clinical biomarker for identification of patients at risk for cognitive impairment.
便秘被认为是帕金森病（PD）的前驱特征之一，越来越多的证据表明胃肠道功能障碍与 PD 患者的认知障碍（CI）有关。
我们在两个独立的初发 PD 患者队列（NILS 队列中 196 例，PPMI 队列中 423 例）中探讨了便秘与 CI 发展的关系。
便秘采用非运动症状量表（NMSS）项目 21[NILS]和帕金森病自主神经功能障碍量表（SCOPA-AUT）项目 5[PPMI]进行临床定义。我们评估了基线时 CI、整体非运动症状负担、运动功能障碍和纹状体多巴胺能神经支配方面存在便秘（PD 伴或不伴便秘）和无便秘（PD 伴或不伴便秘）两组间的差异。Kaplan-Meier 法估计了三年期间两组间 CI 累积发生率的差异。在 PPMI 中，我们随后进行了单变量和多变量 Cox 生存分析，以评估便秘是否能预测 6 年内发生轻度认知障碍或痴呆，包括将便秘和其他已知的 CI 预测因子作为协变量。
两组患者基线时便秘患者的运动和整体非运动负担更大（p<0.05）。Kaplan-Meier 图显示两组患者中便秘患者向 CI 转化更快（p<0.05）。在 PPMI 中，37 例患者在平均 4.9 年的随访期间发展为痴呆，便秘是痴呆发病的独立预测因子（危险比=2.311；p=0.02）。
初发 PD 患者的便秘与认知下降的发展有关，可能是识别有认知障碍风险的患者的临床生物标志物。
