监测早期帕金森病中的30种候选标志物作为疾病进展标志物。
Monitoring of 30 marker candidates in early Parkinson disease as progression markers.
作者信息
Mollenhauer Brit, Zimmermann Johannes, Sixel-Döring Friederike, Focke Niels K, Wicke Tamara, Ebentheuer Jens, Schaumburg Martina, Lang Elisabeth, Trautmann Ellen, Zetterberg Henrik, Taylor Peggy, Friede Tim, Trenkwalder Claudia
机构信息
From Paracelsus-Elena-Klinik (B.M., F.S.-D., T.W., J.E., M.S., E.L., E.T., C.T.), Kassel; Departments of Neurosurgery (B.M., C.T.) and Medical Statistics (T.F.) and Institute of Neuropathology (B.M.), University Medical Centre Göttingen; Psychologische Hochschule Berlin (J.Z.); Department of Neurology/Epileptology and Hertie Institute of Clinical Brain Research (N.K.F.), University of Tübingen, Germany; Clinical Neurochemistry Laboratory (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology (H.Z.), Queen Square, London, UK; and BioLegend (P.T.), Dedham, MA.
出版信息
Neurology. 2016 Jul 12;87(2):168-77. doi: 10.1212/WNL.0000000000002651. Epub 2016 May 6.
OBJECTIVE
This was a longitudinal single-center cohort study to comprehensively explore multimodal progression markers for Parkinson disease (PD) in patients with recently diagnosed PD (n = 123) and age-matched, neurologically healthy controls (HC; n = 106).
METHODS
Thirty tests at baseline and after 24 months covered nonmotor symptoms (NMS), cognitive function, and REM sleep behavior disorder (RBD) by polysomnography (PSG), voxel-based morphometry (VBM) of the brain by MRI, and CSF markers. Linear mixed-effect models were used to estimate differences of rates of change and to provide standardized effect sizes (d) with 95% confidence intervals (CI).
RESULTS
A composite panel of 10 informative markers was identified. Significant relative worsening (PD vs HC) was seen with the following markers: the Unified Parkinson's Disease Rating Scale I (d 0.39; CI 0.09-0.70), the Autonomic Scale for Outcomes in Parkinson's Disease (d 0.25; CI 0.06-0.46), the Epworth Sleepiness Scale (d 0.47; CI 0.24-0.71), the RBD Screening Questionnaire (d 0.44; CI 0.25-0.64), and RBD by PSG (d 0.37; CI 0.19-0.55) as well as VBM units of cortical gray matter (d -0.2; CI -0.3 to -0.09) and hippocampus (d -0.15; CI -0.27 to -0.03). Markers with a relative improvement included the Nonmotor Symptom (Severity) Scale (d -0.19; CI -0.36 to -0.02) and 2 depression scales (Beck Depression Inventory d -0.18; CI -0.36 to 0; Montgomery-Åsberg Depression Rating Scale d -0.26; CI -0.47 to -0.04). Unexpectedly, cognitive measures and select laboratory markers were not significantly changed in PD vs HC participants.
CONCLUSIONS
Current CSF biomarkers and cognitive scales do not represent useful progression markers. However, sleep and imaging measures, and to some extent NMS, assessed using adequate scales, may be more informative markers to quantify progression.
目的
这是一项纵向单中心队列研究，旨在全面探索新诊断的帕金森病（PD）患者（n = 123）及年龄匹配的神经功能正常对照者（HC；n = 106）中帕金森病的多模式进展标志物。
方法
在基线和24个月后进行了30项测试，涵盖非运动症状（NMS）、认知功能，通过多导睡眠图（PSG）评估快速眼动睡眠行为障碍（RBD），通过MRI进行基于体素的脑形态测量（VBM）以及脑脊液标志物。使用线性混合效应模型来估计变化率的差异，并提供具有95%置信区间（CI）的标准化效应量（d）。
结果
确定了一个由10个信息性标志物组成的综合指标。在以下标志物中观察到帕金森病组相对于健康对照组有显著恶化：统一帕金森病评定量表I（d = 0.39；CI 0.09 - 0.70）、帕金森病自主神经功能结局量表（d = 0.25；CI 0.06 - 0.46）、爱泼沃斯思睡量表（d = 0.47；CI 0.24 - 0.71）、RBD筛查问卷（d = 0.44；CI 0.25 - 0.64）、PSG检测的RBD（d = 0.37；CI 0.19 - 0.55）以及皮质灰质的VBM单位（d = -0.2；CI -0.3至-0.09）和海马体（d = -0.15；CI -0.27至-0.03）。有相对改善的标志物包括非运动症状（严重程度）量表（d = -0.19；CI -0.36至-0.02）和2个抑郁量表（贝克抑郁量表d = -0.18；CI -0.36至0；蒙哥马利 - 阿斯伯格抑郁评定量表d = -0.26；CI -0.47至-0.04）。出乎意料的是，帕金森病组与健康对照组参与者的认知测量和特定实验室标志物没有显著变化。
结论
目前的脑脊液生物标志物和认知量表并非有用的进展标志物。然而，使用适当量表评估的睡眠和影像学测量，以及在一定程度上的非运动症状，可能是更能提供信息的量化进展的标志物。
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