Heinzel Sebastian, Roeben Benjamin, Ben-Shlomo Yoav, Lerche Stefanie, Alves Guido, Barone Paolo, Behnke Stefanie, Berendse Henk W, Bloem Bastiaan R, Burn David, Dodel Richard, Grosset Donald G, Hu Michele, Kasten Meike, Krüger Rejko, Moccia Marcello, Mollenhauer Brit, Oertel Wolfgang, Suenkel Ulrike, Walter Uwe, Wirdefeldt Karin, Liepelt-Scarfone Inga, Maetzler Walter, Berg Daniela
Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of TübingenTübingen, Germany; German Center for Neurodegenerative Diseases, University of TübingenTübingen, Germany.
School of Social and Community Medicine, University of Bristol Bristol, UK.
Front Aging Neurosci. 2016 Jun 22;8:147. doi: 10.3389/fnagi.2016.00147. eCollection 2016.
A growing body of evidence supports a prodromal neurodegenerative process preceding the clinical onset of Parkinson's disease (PD). Studies have identified several different prodromal markers that may have the potential to predict the conversion from healthy to clinical PD but use considerably different approaches. We systematically reviewed 35 longitudinal studies reporting prodromal PD features and evaluated the methodological quality across 10 different predefined domains. We found limitations in the following domains: PD diagnosis (57% of studies), prodromal marker assessments (51%), temporal information on prodromal markers or PD diagnosis (34%), generalizability of results (17%), statistical methods (accounting for at least age as confounder; 17%), study design (14%), and sample size (9%). However, no limitations regarding drop-out (or bias investigation), or report of inclusion/exclusion criteria or prodromal marker associations were revealed. Lessons learned from these limitations and additional aspects of current prodromal marker studies in PD are discussed to provide a basis for the evaluation of findings and the improvement of future research in prodromal PD. The observed heterogeneity of studies, limitations and analyses might be addressed in future longitudinal studies using a, yet to be established, modular minimal set of assessments improving comparability of findings and enabling data sharing and combined analyses across studies.
越来越多的证据支持在帕金森病（PD）临床发病之前存在前驱性神经退行性变过程。研究已经确定了几种不同的前驱标志物，它们可能有潜力预测从健康状态向临床PD的转变，但采用的方法差异很大。我们系统回顾了35项报告前驱性PD特征的纵向研究，并评估了10个不同预定义领域的方法学质量。我们发现在以下领域存在局限性：PD诊断（57%的研究）、前驱标志物评估（51%）、前驱标志物或PD诊断的时间信息（34%）、结果的可推广性（17%）、统计方法（至少将年龄作为混杂因素考虑；17%）、研究设计（14%）和样本量（9%）。然而，未发现关于失访（或偏倚调查）、纳入/排除标准报告或前驱标志物关联方面的局限性。讨论了从这些局限性以及当前PD前驱标志物研究的其他方面吸取的经验教训，为评估研究结果和改进未来前驱性PD研究提供依据。研究中观察到的异质性、局限性和分析方法，可能在未来的纵向研究中通过使用一套尚未确定的模块化最小评估集来解决，以提高研究结果的可比性，并实现跨研究的数据共享和联合分析。
