Department of Epidemiology and Biostatistics, College of Human Medicine, Michigan State University, East Lansing, MI, USA.
J Parkinsons Dis. 2018;8(1):1-12. doi: 10.3233/JPD-171238.
Despite recent successes in understanding the genetics of Parkinson's disease (PD), the causes of late-onset sporadic PD remain elusive. Many of the epidemiologic findings on PD etiology have been challenged by alternative explanations such as reverse causation. This is mainly because PD often takes decades to develop before it can be diagnosed late in life. Convincing evidence shows that this prodromal stage of PD is characterized by various prodromal symptoms such as olfactory impairment and rapid-eye-movement sleep behavior disorder (RBD). As they likely reflect PD pathogenesis years, if not decades, before nigrostriatal involvement, research on these symptoms may represent an unprecedented opportunity to dissect the etiology of PD. Using PD prodromal symptoms as intermediate phenotypes, we may be able to identify factors that contribute to the development of these symptoms and factors that modify their progression to clinical PD. Further, this line of research will also enable examinations of novel etiological hypotheses of PD development such as the microbiome and prion hypotheses. In this article, the author used olfactory impairment and RBD as examples to illustrate the promises and challenges of epidemiologic research on prodromal symptoms to understand PD etiology.
尽管近年来在理解帕金森病 (PD) 的遗传学方面取得了一些成功，但散发性迟发性 PD 的病因仍难以捉摸。许多关于 PD 病因的流行病学研究结果都受到了替代解释的挑战，例如反向因果关系。这主要是因为 PD 通常需要几十年的时间才能在生命后期被诊断出来。令人信服的证据表明，PD 的这一前驱阶段的特征是各种前驱症状，如嗅觉障碍和快速眼动睡眠行为障碍 (RBD)。由于它们可能反映了 PD 发病机制在黑质纹状体受累之前的数年甚至数十年，因此对这些症状的研究可能代表了剖析 PD 病因的前所未有的机会。使用 PD 前驱症状作为中间表型，我们也许能够确定导致这些症状发展的因素以及改变其向临床 PD 进展的因素。此外，这一研究领域还将能够检验 PD 发展的新病因假设，如微生物组和朊病毒假说。在这篇文章中，作者以嗅觉障碍和 RBD 为例，说明了使用前驱症状进行流行病学研究以了解 PD 病因的前景和挑战。
