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Evaluation of progression markers in the premotor phase of Parkinson's Disease: The progression markers in the premotor phase study

机译：帕金森氏病运动前期的进展标志物评估：运动前期研究中的进展标志物

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Background: The clinical diagnosis of Parkinson's disease (PD) is proposed to be too late for the application of beneficial neuroprotective treatment. Thus, it is important to identify and follow individuals at risk for PD in order to gain knowledge about the prodromal course of the disease. Substantia nigra hyperechogenicity (SN+) has been confirmed as a risk factor for PD and appears promising as a predictor of PD, particularly in combination with other putative PD markers. We present the design and initial data of a 2-year longitudinal investigation of subjects proposed to be at high risk of developing PD (HR PD), compared to early PD patients and control subjects. The aim of the presented study is to monitor progression of the neurodegenerative process to motor PD. Methods: In total, 40 HRPD, 16 PD and 41 control individuals were recruited. The HRPD subjects had SN+ and additionally either 1 cardinal PD motor sign or 2 further risk (e.g. positive family history) or prodromal markers (e.g. hyposmia). In this cohort, motor function, olfaction, mood and blood markers will be evaluated every 6 months, complemented by a comprehensive clinical, imaging and electrophysiological assessment. Results: PD, HRPD and control subjects did not differ significantly regarding age, but the HRPD group consisted mainly of males (72.5% of HRPD subjects vs. 43.9% of controls; p = 0.013). Mean disease duration in PD patients was 31 months (range 15-56). HRPD subjects were predominantly recruited according to the occurrence of slight motor signs (HRPD 77.5%, PD 100%, p = 0.05; controls 0%, HR PD vs. controls, p 0.017). The Unified Parkinson's Disease Rating Scale motor score (mean, range) indicated that the HRPD group (4, 0-12) had values between those of controls (0, 0-2; p 0.017) and PD subjects (26, 9-55; p 0.017). Among nonmotor symptoms, hyposmia was more common in both HRPD (47.5%) and PD subjects (75%) than in controls (5.1%; p 0.017 for both comparisons). Conclusions: Here, we describe the recruitment of a highly enriched-risk cohort and a promising study design to assess progression to motor PD. Whether the HRPD group indeed suffers from early, PD-specific neurodegeneration remains to be verified in the ongoing follow-up examinations.
机译：背景：帕金森氏病（PD）的临床诊断对于应用有益的神经保护治疗为时已晚。因此，重要的是要识别和追踪有PD危险的个体，以了解有关疾病的前驱过程。黑质高回声性（SN +）已被证实是PD的危险因素，并且有望成为PD的预测指标，特别是与其他推定的PD标志物结合使用时。与早期的PD患者和对照组相比，我们提出了一项为期2年的纵向研究的设计和初始数据，该研究被提议处于发展PD的高风险人群中。本研究的目的是监测神经退行性过程向运动性PD的进展。方法：总共招募了40名HRPD，16名PD和41名对照组。 HRPD受试者患有SN +，另外还有1个主要的PD运动征象或2个其他风险（例如，阳性家族史）或前驱标志物（例如，低渗症）。在该队列中，将每6个月对运动功能，嗅觉，情绪和血液标志物进行评估，并辅以全面的临床，影像学和电生理评估。结果：PD，HRPD和对照组在年龄方面无显着差异，但HRPD组主要由男性组成（HRPD组为72.5％，对照组为43.9％; p = 0.013）。 PD患者的平均病程为31个月（范围15-56）。 HRPD受试者主要根据轻微运动征象的发生而招募（HRPD 77.5％，PD 100％，p = 0.05;对照组0％，HR PD与对照组相比，p <0.017）。统一帕金森氏病评分量表的运动评分（平均值，范围）表明，HRPD组（4，0-12）的值介于对照组（0，0-2; p <0.017）和PD受试者（26，9- 55; p ＜0.017）。在非运动性症状中，HRPD（47.5％）和PD受试者（75％）的低渗症比对照组（5.1％;两个比较的p <0.017）更常见。结论：在这里，我们描述了高风险人群的募集和有希望的研究设计，以评估运动性PD的进展。 HRPD组是否确实患有早期的PD特异性神经退行性疾病，尚需进行中的后续检查进行验证。

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