纵向评估的帕金森病队列中的脑脊液神经丝轻链：年龄效应和认知轨迹

CSF NFL in a Longitudinally Assessed PD Cohort: Age Effects and Cognitive Trajectories.

作者信息

Lerche Stefanie, Wurster Isabel, Röben Benjamin, Zimmermann Milan, Machetanz Gerrit, Wiethoff Sarah, Dehnert Monique, Rietschel Lea, Riebenbauer Benjamin, Deuschle Christian, Stransky Elke, Lieplt-Scarfone Inga, Gasser Thomas, Brockmann Kathrin

机构信息

Center of Neurology, Department of Neurodegeneration and Hertie-Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.

German Center for Neurodegenerative Diseases, University of Tuebingen, Tuebingen, Germany.

出版信息

Mov Disord. 2020 Jul;35(7):1138-1144. doi: 10.1002/mds.28056. Epub 2020 May 23.

DOI:10.1002/mds.28056

PMID:32445500

Abstract

BACKGROUND

Neurofilament light protein is an unspecific biofluid marker that reflects the extent of neuronal/axonal damage and thereby offers the chance monitor disease severity and progression. The objective of this study was to investigate cerebrospinal fluid (CSF) levels of neurofilament light protein in Parkinson's disease (PD) patients with clinical trajectories of motor and cognitive function longitudinally.

METHODS

CSF neurofilament light protein levels were assessed in 371 PD , 126 genetic PD patients (91 PD , 8 PD , 21 PD , 6 PD ), and 71 healthy controls. Participants were followed up longitudinally for up to 8 years.

RESULTS

At baseline, mean CSF neurofilament light protein levels were highest in PD patients with cognitive impairment (Montreal Cognitive Assessment score ≤ 25; 1207 pg/mL) but also higher in PD patients with normal cognitive function (757 pg/mL) compared with healthy controls (593 pg/mL; P ≤ 0.001). In healthy controls and in PD patients older age was associated with higher CSF levels of neurofilament light protein (P ≤ 0.001). In PD patients, male gender, older age at onset, longer disease duration, higher Hoehn and Yahr stages, higher UPDRS-III scores, and lower Montreal Cognitive Assessment scores were associated with higher CSF levels of neurofilament light protein (P < 0.01). In patients who developed cognitive impairment during study, CSF neurofilament light protein levels prior to conversion to cognitive impairment were not significantly different compared with CSF neurofilament light protein levels of patients who remained cognitively normal.

CONCLUSIONS

Increased CSF levels of neurofilament light protein are associated with cognitive decline and motor impairment in PD. However, this increase seems not a very early event and does not mark the conversion to cognitive impairment beforehand. Therefore, the predictive value needs to be discussed critically. © 2020 International Parkinson and Movement Disorder Society.

摘要

背景

神经丝轻链蛋白是一种非特异性生物流体标志物，可反映神经元/轴突损伤程度，从而为监测疾病严重程度和进展提供机会。本研究的目的是纵向调查帕金森病（PD）患者运动和认知功能临床轨迹中脑脊液（CSF）神经丝轻链蛋白水平。

方法

对371例PD患者、126例遗传性PD患者（91例PD、8例PD、21例PD、6例PD）和71名健康对照者的脑脊液神经丝轻链蛋白水平进行评估。参与者纵向随访长达8年。

结果

在基线时，认知障碍的PD患者（蒙特利尔认知评估评分≤25；1207 pg/mL）的脑脊液神经丝轻链蛋白平均水平最高，但与健康对照者（593 pg/mL；P≤0.001）相比，认知功能正常的PD患者（757 pg/mL）的该水平也更高。在健康对照者和PD患者中，年龄较大与脑脊液神经丝轻链蛋白水平较高相关（P≤0.001）。在PD患者中，男性、发病年龄较大、病程较长、Hoehn和Yahr分期较高、UPDRS-III评分较高以及蒙特利尔认知评估评分较低与脑脊液神经丝轻链蛋白水平较高相关（P<0.01）。在研究期间发生认知障碍的患者中，转化为认知障碍之前的脑脊液神经丝轻链蛋白水平与认知功能保持正常的患者的脑脊液神经丝轻链蛋白水平相比无显著差异。