Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan.
Department of Neurology, Morinomiya Hospital, Osaka, Japan.
PLoS One. 2022 Dec 30;17(12):e0279747. doi: 10.1371/journal.pone.0279747. eCollection 2022.
Patients with Parkinson's disease (PD) often suffer from sleep disturbances, including excessive daytime sleepiness (EDS) and rapid eye movement sleep behavior disorder (RBD). These symptoms are also experienced by patients with narcolepsy, which is characterized by orexin neuronal loss. In PD, a decrease in orexin neurons is observed pathologically, but the association between sleep disturbance in PD and cerebrospinal fluid (CSF) orexin levels is still unclear. This study aimed to clarify the role of orexin as a biomarker in patients with PD. CSF samples were obtained from a previous cohort study conducted between 2015 and 2020. We cross-sectionally and longitudinally examined the association between CSF orexin levels, sleep, and clinical characteristics. We analyzed 78 CSF samples from 58 patients with PD and 21 samples from controls. CSF orexin levels in patients with PD (median = 272.0 [interquartile range = 221.7-334.5] pg/mL) were lower than those in controls (352.2 [296.2-399.5] pg/mL, p = 0.007). There were no significant differences in CSF orexin levels according to EDS, RBD, or the use of dopamine agonists. Moreover, no significant correlation was observed between CSF orexin levels and clinical characteristics by multiple linear regression analysis. Furthermore, the longitudinal changes in orexin levels were also not correlated with clinical characteristics. This study showed decreased CSF orexin levels in patients with PD, but these levels did not show any correlation with any clinical characteristics. Our results suggest the limited efficacy of CSF orexin levels as a biomarker for PD, and that sleep disturbances may also be affected by dysfunction of the nervous system other than orexin, or by dopaminergic treatments in PD. Understanding the reciprocal role of orexin among other neurotransmitters may provide a better treatment strategy for sleep disturbance in patients with PD.
帕金森病（PD）患者常伴有睡眠障碍，包括日间过度嗜睡（EDS）和快速眼动睡眠行为障碍（RBD）。这些症状也发生在发作性睡病患者中，其特征是食欲素神经元丧失。在 PD 中，病理上观察到食欲素神经元减少，但 PD 中睡眠障碍与脑脊液（CSF）食欲素水平之间的关联仍不清楚。本研究旨在阐明食欲素作为 PD 患者生物标志物的作用。CSF 样本来自 2015 年至 2020 年期间进行的一项先前队列研究。我们横断性和纵向研究了 CSF 食欲素水平、睡眠和临床特征之间的关系。我们分析了 58 例 PD 患者和 21 例对照的 78 例 CSF 样本。PD 患者的 CSF 食欲素水平（中位数=272.0 [四分位距=221.7-334.5] pg/mL）低于对照组（352.2 [296.2-399.5] pg/mL，p=0.007）。根据 EDS、RBD 或多巴胺激动剂的使用，CSF 食欲素水平没有显著差异。此外，通过多元线性回归分析，CSF 食欲素水平与临床特征之间也没有观察到显著相关性。此外，纵向变化的食欲素水平也与临床特征无关。本研究表明 PD 患者的 CSF 食欲素水平降低，但这些水平与任何临床特征均无相关性。我们的结果表明，CSF 食欲素水平作为 PD 的生物标志物的疗效有限，睡眠障碍也可能受除食欲素以外的神经系统功能障碍或 PD 中的多巴胺治疗的影响。了解食欲素与其他神经递质之间的相互作用可能为 PD 患者的睡眠障碍提供更好的治疗策略。
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