睡眠障碍与帕金森病的双向关系

doi:10.16150/j.1671-2870.2026.02.004

摘要/Abstract

摘要：

帕金森病（Parkinson’s disease， PD）是第二大常见的神经退行性疾病，与阿尔茨海默病（Alzheimer’s disease， AD）共享部分核心病理特征，即错误折叠及神经毒性蛋白积累引发神经元功能障碍和死亡，且均为遗传与非遗传因素共同作用的多因素疾病。其中，由于非遗传因素的可调控性，成为了疾病预防与治疗策略开发的核心靶点，睡眠便是极具研究价值的一类非遗传因素。睡眠障碍在PD患者中高度普遍发生，而在AD中已证实睡眠障碍与疾病存在“既是后果也是危险因素”的双向关系，该双向关系是否存在于PD中尚未明确。PD患者睡眠障碍患病率达60%~98%，涵盖失眠、日间过度嗜睡、快速眼动睡眠行为障碍（rapid eye movement sleep behavior disorder， RBD）等多种类型。多导睡眠图（polysomnogram， PSG）显示，PD患者总睡眠时间、睡眠效率、各阶段睡眠占比均较正常人显著降低，入睡后觉醒时间、N1期睡眠占比及快速眼动潜伏期延长。睡眠障碍与PD的双向关联研究显示，RBD常为PD的前驱症状，特发性RBD患者10年随访中40%~50%进展为PD，且脑脊液α突触核蛋白（α-synuclein， α-Syn）阳性患者转化率更高；慢性失眠、睡眠片段化、慢波睡眠减少均可能增加PD发病风险或加速疾病进展，也有研究提示，睡眠障碍也可能是PD的早期症状。两者间的因果关系有待进一步明确，两者的关联机制复杂。PD患者黑质-纹状体通路多巴胺能神经元变性、非多巴胺能系统受累、α-Syn在睡眠调控脑区聚集，以及非运动症状和治疗药物影响，共同导致睡眠障碍；而睡眠障碍可通过破坏蛋白质稳态，增加α-Syn分泌与聚集，削弱类淋巴系统清除功能，诱发神经炎症等途径，加剧PD病理进程。基于现有研究，睡眠有望成为PD预防与治疗的新靶点。未来需通过严谨的前瞻性队列研究和随机对照试验，明确二者因果关系，开发特异性生物标志物，优化睡眠干预方案，将睡眠管理纳入PD综合防治体系，以延缓疾病进展、改善患者预后。

关键词: 帕金森病, α突触核蛋白, 睡眠障碍

Abstract:

Parkinson's disease (PD), the second most common neurodegenerative disorder, shares some core pathological features with Alzheimer's disease (AD), namely the accumulation of misfolded neurotoxic proteins leading to neuronal dysfunction and death, and both are multifactorial diseases resulting from the combined effects of genetic and non-genetic factors. Among these, non-genetic factors, due to their modifiability, have become key targets for disease prevention and therapeutic strategy development, and sleep is a non-genetic factor of great research value. Sleep disorders are highly prevalent in patients with PD, while in AD it has been demonstrated that sleep disorders have a bidirectional relationship with the disease, acting as both a consequence and a risk factor. However, whether such a relationship exists in PD remains unclear. The prevalence of sleep disorders in PD patients ranges from 60% to 98%, encompassing various types such as insomnia, excessive daytime sleepiness, and rapid eye movement sleep behavior disorder (RBD). Polysomnogram (PSG) shows that PD patients exhibit significantly reduced total sleep duration, sleep efficiency, and proportions of sleep stages, along with prolonged wake time after sleep onset, increased proportions of N1 sleep, and extended rapid eye movement latency. Research on the bidirectional relationship between sleep disorders and PD shows that RBD is often a prodromal symptom of PD, with 40% to 50% of idiopathic RBD patients progressing to PD during a 10-year follow-up, and a higher conversion rate observed in patients with cerebrospinal fluid α-Syn positivity. Chronic insomnia, sleep fragmentation, and reduced slow-wave sleep may increase the risk of PD onset or accelerate disease progression. Some studies suggest that sleep disorders could also be early symptoms of PD. The causal relationships between the two remain to be further clarified, and the underlying mechanisms are complex. In PD patients, degeneration of dopaminergic neurons in the substantia nigra-striatal pathway, involvement of non-dopaminergic systems, accumulation of α-Syn in brain regions regulating sleep, as well as non-motor symptoms and therapeutic drug effects collectively contribute to sleep disorders. Conversely, sleep disturbances may exacerbate the pathological progression of PD by disrupting protein homeostasis, increasing α-Syn secretion and aggregation, impairing glymphatic system clearance function, and inducing neuroinflammation. Based on current research, sleep is emerging as a novel target for PD prevention and treatment. Future studies should employ rigorous prospective cohort studies and randomized controlled trials to establish causal relationships between these two factors, develop specific biomarkers, optimize sleep intervention protocols, and integrate sleep management into the comprehensive PD prevention and treatment system to delay disease progression and improve patient outcomes.

Key words: Parkinson's disease, α-synuclein, Sleep disorders

中图分类号:

R444
R742

武冬冬, 陈海波. 睡眠障碍与帕金森病的双向关系[J]. 诊断学理论与实践, 2026, 25(02): 141-147.

WU Dongdong, CHEN Haibo. Bidirectional relationship between sleep disorders and Parkinson's disease[J]. Journal of Diagnostics Concepts & Practice, 2026, 25(02): 141-147.

图/表 1

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