Shi Ming-Yu, Ma Cheng-Cheng, Chen Fang-Fang, Zhou Xiao-Yu, Li Xue, Tang Chuan-Xi, Zhang Lin, Gao Dian-Shuai
Department of Neurology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou; Department of Neurology, the First People's Hospital of Yancheng, Yancheng, Jiangsu Province, China.
Department of Neurobiology and Anatomy, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
Neural Regen Res. 2021 May;16(5):885-892. doi: 10.4103/1673-5374.297091.
Glial cell line-derived neurotrophic factor (GDNF) plays an important role in the protection of dopaminergic neurons, but there are few reports of the relationship between GDNF and its precursors (α-pro-GDNF and β-pro-GDNF) and cognitive impairment in Parkinson's disease. This study aimed to investigate the relationship between the serum levels of GDNF and its precursors and cognitive impairment in Parkinson's disease, and to assess their potential as a diagnostic marker. Fifty-three primary outpatients and hospitalized patients with Parkinson's disease (23 men and 30 women) with an average age of 66.58 years were enrolled from the Affiliated Hospital of Xuzhou Medical University of China in this case-control study. The patients were divided into the Parkinson's disease with cognitive impairment group (n = 27) and the Parkinson's disease with normal cognitive function group (n = 26) based on their Mini-Mental State Examination, Montreal Cognitive Assessment, and Clinical Dementia Rating scores. In addition, 26 age- and sex-matched healthy subjects were included as the healthy control group. Results demonstrated that serum GDNF levels were significantly higher in the Parkinson's disease with normal cognitive function group than in the other two groups. There were no significant differences in GDNF precursor levels among the three groups. Correlation analysis revealed that serum GDNF levels, GDNF/α-pro-GDNF ratios, and GDNF/β-pro-GDNF ratios were moderately or highly correlated with the Mini-Mental State Examination, Montreal Cognitive Assessment, and Clinical Dementia Rating scores. To explore the risk factors for cognitive impairment in patients with Parkinson's disease, logistic regression analysis and stepwise linear regression analysis were performed. Both GDNF levels and Hoehn-Yahr stage were risk factors for cognitive impairment in Parkinson's disease, and were the common influencing factors for cognitive scale scores. Neither α-pro-GDNF nor β-pro-GDNF was risk factors for cognitive impairment in Parkinson's disease. A receiver operating characteristic curve of GDNF was generated to predict cognitive function in Parkinson's disease (area under the curve = 0.859). This result indicates that the possibility that serum GDNF can correctly distinguish whether patients with Parkinson's disease have cognitive impairment is 0.859. Together, these results suggest that serum GDNF may be an effective diagnostic marker for cognitive impairment in Parkinson's disease. However, α-pro-GDNF and β-pro-GDNF are not useful for predicting cognitive impairment in this disease. This study was approved by Ethics Committee of the Affiliated Hospital of Xuzhou Medical University, China (approval No. XYFY2017-KL047-01) on November 30, 2017.
胶质细胞源性神经营养因子（GDNF）在保护多巴胺能神经元方面发挥着重要作用，但关于GDNF及其前体（α-前体GDNF和β-前体GDNF）与帕金森病认知障碍之间关系的报道较少。本研究旨在探讨帕金森病患者血清中GDNF及其前体水平与认知障碍之间的关系，并评估它们作为诊断标志物的潜力。在这项病例对照研究中，从中国徐州医科大学附属医院招募了53例原发性门诊和住院帕金森病患者（23例男性和30例女性），平均年龄为66.58岁。根据简易精神状态检查表、蒙特利尔认知评估量表和临床痴呆评定量表评分，将患者分为帕金森病伴认知障碍组（n = 27）和帕金森病认知功能正常组（n = 26）。此外，纳入26例年龄和性别匹配的健康受试者作为健康对照组。结果显示，帕金森病认知功能正常组的血清GDNF水平显著高于其他两组。三组之间GDNF前体水平无显著差异。相关性分析表明，血清GDNF水平、GDNF/α-前体GDNF比值和GDNF/β-前体GDNF比值与简易精神状态检查表、蒙特利尔认知评估量表和临床痴呆评定量表评分呈中度或高度相关。为了探讨帕金森病患者认知障碍的危险因素，进行了逻辑回归分析和逐步线性回归分析。GDNF水平和Hoehn-Yahr分期均为帕金森病认知障碍的危险因素，且是认知量表评分的共同影响因素。α-前体GDNF和β-前体GDNF均不是帕金森病认知障碍的危险因素。生成了GDNF的受试者工作特征曲线以预测帕金森病的认知功能（曲线下面积 = 0.859）。这一结果表明血清GDNF正确区分帕金森病患者是否存在认知障碍的可能性为0.859。综上所述，这些结果提示血清GDNF可能是帕金森病认知障碍的有效诊断标志物。然而，α-前体GDNF和β-前体GDNF对预测该疾病的认知障碍并无帮助。本研究于2017年11月30日获得中国徐州医科大学附属医院伦理委员会批准（批准号：XYFY2017-KL047-01）。
