帕金森病与阻塞性睡眠呼吸暂停共病的双向关联及潜在机制研究进展
Bidirectional Association and Underlying Mechanisms of Comorbid Parkinson’s Disease and Obstructive Sleep Apnea: A Review
DOI: 10.12677/acm.2026.1682890, PDF,   
作者: 刘 颖, 王林芝, 张睿怡：成都中医药大学临床医学院，四川 成都；余葱葱*：四川省中西医结合医院亚健康中心，四川 成都；梁静涛*：成都中医药大学附属医院神经内科，四川 成都
关键词: 帕金森病；阻塞性睡眠呼吸暂停；α-突触核蛋白；神经退行性变；神经炎症；脑类淋巴系统；Parkinson’s Disease； Obstructive Sleep Apnea； α-Synuclein； Neurodegeneration； Neuroinflammation； Glymphatic System
摘要: 阻塞性睡眠呼吸暂停(obstructive sleep apnea, OSA)是帕金森病(Parkinson’s disease, PD)患者常见且可干预的睡眠相关呼吸障碍之一。现有研究提示，PD与OSA可能存在双向关联。一方面，PD相关脑干核团受累、自主神经功能障碍、上气道神经肌肉控制异常及夜间运动减少，可能增加OSA发生或加重的风险；另一方面，OSA所致间歇性低氧、睡眠片段化、氧化应激、神经炎症及脑类淋巴系统功能受损，可能增加PD患者非运动症状负担，并与认知、情绪及生活质量下降相关。然而，目前相关证据多来自横断面研究、回顾性队列、动物实验及影像学相关研究，尚不足以证明OSA可直接加速PD病理进展或作为明确疾病修饰因素。本文围绕PD合并OSA的流行病学特征、潜在机制、临床表现及现有诊疗手段进行综述，以期为PD合并OSA的识别和综合干预提供参考。
Abstract: Obstructive sleep apnea (OSA) is one of the common and potentially modifiable sleep-related breathing disorders in patients with Parkinson’s disease (PD). Current evidence suggests a possible bidirectional association between PD and OSA. On the one hand, PD-related involvement of brainstem nuclei, autonomic dysfunction, impaired neuromuscular control of the upper airway, and reduced nocturnal mobility may increase the risk of developing or worsening OSA. On the other hand, intermittent hypoxia, sleep fragmentation, oxidative stress, neuroinflammation, and impairment of the brain glymphatic system induced by OSA may increase the burden of non-motor symptoms in patients with PD and may be associated with declines in cognition, mood, and quality of life. However, the existing evidence is largely derived from cross-sectional studies, retrospective cohorts, animal experiments, and neuroimaging correlation studies, and remains insufficient to demonstrate that OSA directly accelerates PD pathological progression or serves as a definitive disease-modifying factor. This review summarizes the epidemiological characteristics, potential mechanisms, clinical manifestations, and current diagnostic and therapeutic approaches for comorbid OSA in PD, with the aim of providing a reference for the recognition and comprehensive management of OSA in patients with PD.
文章引用：刘颖, 王林芝, 张睿怡, 余葱葱, 梁静涛. 帕金森病与阻塞性睡眠呼吸暂停共病的双向关联及潜在机制研究进展[J]. 临床医学进展, 2026, 16(8): 1157-1166. https://doi.org/10.12677/acm.2026.1682890

参考文献

[1] 中华医学会神经病学分会帕金森病及运动障碍学组, 中国医师协会神经内科分会帕金森病及运动障碍学组. 帕金森病非运动症状管理专家共识(2020) [J]. 中华医学杂志, 2020, 100(27): 2084-2091.
[2] Iranzo, A., Cochen De Cock, V., Fantini, M.L., Pérez-Carbonell, L. and Trotti, L.M. (2024) Sleep and Sleep Disorders in People with Parkinson’s Disease. The Lancet Neurology, 23, 925-937.
https://doi.org/10.1016/s1474-4422(24)00170-4
[3] Si, T.L., Wang, Y.Y., Li, J.X., Bai, W., Sun, H., Rao, S., et al. (2025) Poor Sleep Quality among Patients with Parkinson’s Disease: A Meta-Analysis and Systematic Review. Frontiers in Psychiatry, 16, Article ID: 1606743.
https://doi.org/10.3389/fpsyt.2025.1606743
[4] 中华医学会神经病学分会帕金森病及运动障碍学组, 中国医师协会神经内科医师分会帕金森病及运动障碍学组. 中国帕金森病睡眠障碍管理专家共识[J]. 中华神经科杂志, 2022, 55(5): 441-451.
[5] Yeghiazarians, Y., Jneid, H., Tietjens, J.R., Redline, S., Brown, D.L., El-Sherif, N., et al. (2021) Obstructive Sleep Apnea and Cardiovascular Disease: A Scientific Statement from the American Heart Association. Circulation, 144, e56-e67.
https://doi.org/10.1161/cir.0000000000000988
[6] Wang, J.D.J., Chua, N.Y.M., Chan, L. and Tan, E. (2025) Obstructive Sleep Apnea and Parkinson’s Disease: Bidirectional Clinical and Pathophysiologic Links. International Journal of Molecular Sciences, 26, Article 3762.
https://doi.org/10.3390/ijms26083762
[7] Jeon, S.H., Hwang, Y.S., Oh, S.Y., Shin, B., Kang, M.G., Lee, M.G., et al. (2023) Bidirectional Association between Parkinson’s Disease and Obstructive Sleep Apnea: A Cohort Study. Journal of Clinical Sleep Medicine, 19, 1615-1623.
https://doi.org/10.5664/jcsm.10596
[8] Maggi, G., Giacobbe, C., Iannotta, F., Santangelo, G. and Vitale, C. (2023) Prevalence and Clinical Aspects of Obstructive Sleep Apnea in Parkinson Disease: A Meta‐Analysis. European Journal of Neurology, 31, e16109.
https://doi.org/10.1111/ene.16109
[9] Aini, N., Putri, A.R., Banda, K.J. and Janitra, F.E. (2024) Meta-Analysis of the Prevalence of Obstructive Sleep Apnea and Associated Risk Factors among Parkinson’s Disease. Sleep and Biological Rhythms, 23, 101-112.
https://doi.org/10.1007/s41105-024-00561-w
[10] Braak, H., Tredici, K.D., Rüb, U., de Vos, R.A.I., Jansen Steur, E.N.H. and Braak, E. (2003) Staging of Brain Pathology Related to Sporadic Parkinson’s Disease. Neurobiology of Aging, 24, 197-211.
https://doi.org/10.1016/s0197-4580(02)00065-9
[11] Zoccal, D.B., Furuya, W.I., Bassi, M., Colombari, D.S.A. and Colombari, E. (2014) The Nucleus of the Solitary Tract and the Coordination of Respiratory and Sympathetic Activities. Frontiers in Physiology, 5, Article ID: 238.
https://doi.org/10.3389/fphys.2014.00238
[12] Van Egroo, M., Koshmanova, E., Vandewalle, G. and Jacobs, H.I.L. (2022) Importance of the Locus Coeruleus-Norepinephrine System in Sleep-Wake Regulation: Implications for Aging and Alzheimer’s Disease. Sleep Medicine Reviews, 62, Article 101592.
https://doi.org/10.1016/j.smrv.2022.101592
[13] Aung, O., Amorim, M.R., Mendelowitz, D. and Polotsky, V.Y. (2024) Revisiting the Role of Serotonin in Sleep-Disordered Breathing. International Journal of Molecular Sciences, 25, Article 1483.
https://doi.org/10.3390/ijms25031483
[14] Gonye, E.C. and Bayliss, D.A. (2023) Criteria for Central Respiratory Chemoreceptors: Experimental Evidence Supporting Current Candidate Cell Groups. Frontiers in Physiology, 14, Article ID: 1241662.
https://doi.org/10.3389/fphys.2023.1241662
[15] Horner, R.L., Hughes, S.W. and Malhotra, A. (2014) State-Dependent and Reflex Drives to the Upper Airway: Basic Physiology with Clinical Implications. Journal of Applied Physiology, 116, 325-336.
https://doi.org/10.1152/japplphysiol.00531.2013
[16] Li, Y., Tong, Q., Wang, Y., Cheng, Y., Geng, Y., Tian, T., et al. (2024) Phosphorylated Α-Synuclein Deposited in Schwann Cells Interacting with TLR2 Mediates Cell Damage and Induces Parkinson’s Disease Autonomic Dysfunction. Cell Death Discovery, 10, Article No. 52.
https://doi.org/10.1038/s41420-024-01824-8
[17] Cheng, Y., Tong, Q., Yuan, Y., Song, X., Jiang, W., Wang, Y., et al. (2023) Α-Synuclein Induces Prodromal Symptoms of Parkinson’s Disease via Activating TLR2/MyD88/NF-κB Pathway in Schwann Cells of Vagus Nerve in a Rat Model. Journal of Neuroinflammation, 20, Article No. 36.
https://doi.org/10.1186/s12974-023-02720-1
[18] Butkovich, L.M., Houser, M.C. and Tansey, M.G. (2018) Α-Synuclein and Noradrenergic Modulation of Immune Cells in Parkinson’s Disease Pathogenesis. Frontiers in Neuroscience, 12, Article No. 626.
https://doi.org/10.3389/fnins.2018.00626
[19] Prabhakar, N.R., Peng, Y. and Nanduri, J. (2020) Hypoxia-Inducible Factors and Obstructive Sleep Apnea. Journal of Clinical Investigation, 130, 5042-5051.
https://doi.org/10.1172/jci137560
[20] Lv, R., Liu, X., Zhang, Y., Dong, N., Wang, X., He, Y., et al. (2023) Pathophysiological Mechanisms and Therapeutic Approaches in Obstructive Sleep Apnea Syndrome. Signal Transduction and Targeted Therapy, 8, Article No. 218.
https://doi.org/10.1038/s41392-023-01496-3
[21] Dissanayake, H.U., Bin, Y.S., Ucak, S., de Chazal, P., Sutherland, K. and Cistulli, P.A. (2021) Association between Autonomic Function and Obstructive Sleep Apnea: A Systematic Review. Sleep Medicine Reviews, 57, Article 101470.
https://doi.org/10.1016/j.smrv.2021.101470
[22] Singh, K.K., Ghosh, S., Bhola, A., Verma, P., Amist, A.D., Sharma, H., et al. (2024) Sleep and Immune System Crosstalk: Implications for Inflammatory Homeostasis and Disease Pathogenesis. Annals of Neurosciences, 32, 196-206.
https://doi.org/10.1177/09727531241275347
[23] Boche, D., Perry, V.H. and Nicoll, J.A.R. (2013) Review: Activation Patterns of Microglia and Their Identification in the Human Brain. Neuropathology and Applied Neurobiology, 39, 3-18.
https://doi.org/10.1111/nan.12011
[24] Dong, H., Zhang, X., Duan, Y., He, Y., Zhao, J., Wang, Z., et al. (2024) Hypoxia Inducible Factor-1α Regulates Microglial Innate Immune Memory and the Pathology of Parkinson’s Disease. Journal of Neuroinflammation, 21, Article No. 80.
https://doi.org/10.1186/s12974-024-03070-2
[25] Dong, N. and Yue, H. (2025) Advances in Immunology of Obstructive Sleep Apnea: Mechanistic Insights, Clinical Impact, and Therapeutic Perspectives. Frontiers in Immunology, 16, Article ID: 1654450.
https://doi.org/10.3389/fimmu.2025.1654450
[26] Shi, Y., Guo, X., Zhang, J., Zhou, H., Sun, B. and Feng, J. (2018) DNA Binding Protein HMGB1 Secreted by Activated Microglia Promotes the Apoptosis of Hippocampal Neurons in Diabetes Complicated with Osa. Brain, Behavior, and Immunity, 73, 482-492.
https://doi.org/10.1016/j.bbi.2018.06.012
[27] Puech, C., Badran, M., Runion, A.R., Barrow, M.B., Cataldo, K. and Gozal, D. (2023) Cognitive Impairments, Neuroinflammation and Blood-Brain Barrier Permeability in Mice Exposed to Chronic Sleep Fragmentation during the Daylight Period. International Journal of Molecular Sciences, 24, Article 9880.
https://doi.org/10.3390/ijms24129880
[28] Zhu, W., Hu, Y., Shi, Y., Bao, H., Cheng, X., Jiang, M., et al. (2025) Sleep Deprivation Accelerates Parkinson’s Disease via Modulating Gut Microbiota Associated Microglial Activation and Oxidative Stress. Microbiological Research, 293, Article 128077.
https://doi.org/10.1016/j.micres.2025.128077
[29] Iliff, J.J., Wang, M., Liao, Y., Plogg, B.A., Peng, W., Gundersen, G.A., et al. (2012) A Paravascular Pathway Facilitates CSF Flow through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid Β. Science Translational Medicine, 4, 147ra111.
https://doi.org/10.1126/scitranslmed.3003748
[30] Xie, L., Kang, H., Xu, Q., Chen, M.J., Liao, Y., Thiyagarajan, M., et al. (2013) Sleep Drives Metabolite Clearance from the Adult Brain. Science, 342, 373-377.
https://doi.org/10.1126/science.1241224
[31] Zhai, M.R., Pan, J., Wu, Z.H., He, Y., Zhang, K., Ren, L., et al. (2026) Chronic Intermittent Hypoxia Increases Parkinson’s Disease Susceptibility via PPARα-Mediated Lipid Droplet-Mitochondrial Dysfunction. Theranostics, 16, 2466-2487.
https://doi.org/10.7150/thno.122944
[32] Nepozitek, J., Marecek, S., Rottova, V., Dostalova, S., Krajca, T., Keller, J., et al. (2025) Glymphatic Dysfunction Evidenced by DTI-ALPS Is Related to Obstructive Sleep Apnea Intensity in Newly Diagnosed Parkinson’s Disease. npj Parkinson’s Disease, 11, Article No. 160.
https://doi.org/10.1038/s41531-025-01018-8
[33] Lee, H., Lee, D.A., Shin, K.J. and Park, K.M. (2022) Glymphatic System Dysfunction in Obstructive Sleep Apnea Evidenced by DTI-ALPS. Sleep Medicine, 89, 176-181.
https://doi.org/10.1016/j.sleep.2021.12.013
[34] Ju, Y.S., Finn, M.B., Sutphen, C.L., Herries, E.M., Jerome, G.M., Ladenson, J.H., et al. (2016) Obstructive Sleep Apnea Decreases Central Nervous System-Derived Proteins in the Cerebrospinal Fluid. Annals of Neurology, 80, 154-159.
https://doi.org/10.1002/ana.24672
[35] Román, G.C., Jackson, R.E., Fung, S.H., Zhang, Y.J. and Verma, A.K. (2019) Sleep-Disordered Breathing and Idiopathic Normal-Pressure Hydrocephalus: Recent Pathophysiological Advances. Current Neurology and Neuroscience Reports, 19, Article No. 39.
https://doi.org/10.1007/s11910-019-0952-9
[36] Cori, J.M., O’Donoghue, F.J. and Jordan, A.S. (2018) Sleeping Tongue: Current Perspectives of Genioglossus Control in Healthy Individuals and Patients with Obstructive Sleep Apnea. Nature and Science of Sleep, 10, 169-179.
https://doi.org/10.2147/nss.s143296
[37] Aquino, Y.C., Cabral, L.M., Miranda, N.C., Naccarato, M.C., Falquetto, B., Moreira, T.S., et al. (2022) Respiratory Disorders of Parkinson’s Disease. Journal of Neurophysiology, 127, 1-15.
https://doi.org/10.1152/jn.00363.2021
[38] Mu, L., Sobotka, S., Chen, J., Su, H., Sanders, I., Adler, C.H., et al. (2013) Alpha-Synuclein Pathology and Axonal Degeneration of the Peripheral Motor Nerves Innervating Pharyngeal Muscles in Parkinson Disease. Journal of Neuropathology & Experimental Neurology, 72, 119-129.
https://doi.org/10.1097/nen.0b013e3182801cde
[39] Bahia, C.M.C.S., Pereira, J.S. and Lopes, A.J. (2018) Laryngopharyngeal Motor Dysfunction and Obstructive Sleep Apnea in Parkinson’s Disease. Sleep and Breathing, 23, 543-550.
https://doi.org/10.1007/s11325-018-1729-0
[40] Fogel, R.B., Trinder, J., White, D.P., Malhotra, A., Raneri, J., Schory, K., et al. (2005) The Effect of Sleep Onset on Upper Airway Muscle Activity in Patients with Sleep Apnoea versus Controls. The Journal of Physiology, 564, 549-562.
https://doi.org/10.1113/jphysiol.2005.083659
[41] Walsh, J.H., Maddison, K.J., Platt, P.R., et al. (2008) Influence of Head Extension, Flexion, and Rotation on Collapsibility of the Passive Upper Airway. Sleep, 31, 1440-1447.
[42] Sommerauer, M., Werth, E., Poryazova, R., Gavrilov, Y.V., Hauser, S. and Valko, P.O. (2015) Bound to Supine Sleep: Parkinson’s Disease and the Impact of Nocturnal Immobility. Parkinsonism & Related Disorders, 21, 1269-1272.
https://doi.org/10.1016/j.parkreldis.2015.08.010
[43] Landry, S.A., Beatty, C., Thomson, L.D.J., Wong, A., Edwards, B.A., Hamilton, G.S., et al. (2023) A Review of Supine Position Related Obstructive Sleep Apnea: Classification, Epidemiology, Pathogenesis and Treatment. Sleep Medicine Reviews, 72, Article 101847.
https://doi.org/10.1016/j.smrv.2023.101847
[44] Doherty, K.M., van de Warrenburg, B.P., Peralta, M.C., Silveira-Moriyama, L., Azulay, J., Gershanik, O.S., et al. (2011) Postural Deformities in Parkinson’s Disease. The Lancet Neurology, 10, 538-549.
https://doi.org/10.1016/s1474-4422(11)70067-9
[45] Jansen, E.N.H. and Meerwaldt, J.D. (1988) Madopar HBS in Parkinson Patients with Nocturnal Akinesia. Clinical Neurology and Neurosurgery, 90, 35-39.
https://doi.org/10.1016/s0303-8467(88)80007-6
[46] Vincken, W.G., Darauay, C.M. and Cosio, M.G. (1989) Reversibility of Upper Airway Obstruction after Levodopa Therapy in Parkinson’s Disease. Chest, 96, 210-212.
https://doi.org/10.1378/chest.96.1.210
[47] Gros, P., Mery, V.P., Lafontaine, A., Robinson, A., Benedetti, A., Kimoff, R.J., et al. (2015) Obstructive Sleep Apnea in Parkinson’s Disease Patients: Effect of Sinemet CR Taken at Bedtime. Sleep and Breathing, 20, 205-212.
https://doi.org/10.1007/s11325-015-1208-9
[48] Shen, Y., Shen, Y., Dong, Z., Pan, P., Shi, H. and Liu, C. (2020) Obstructive Sleep Apnea in Parkinson’s Disease: A Study in 239 Chinese Patients. Sleep Medicine, 67, 237-243.
https://doi.org/10.1016/j.sleep.2019.11.1251
[49] Valko, P.O., Hauser, S., Sommerauer, M., Werth, E. and Baumann, C.R. (2014) Observations on Sleep-Disordered Breathing in Idiopathic Parkinson’s Disease. PLOS ONE, 9, e100828.
https://doi.org/10.1371/journal.pone.0100828
[50] Trenkwalder, C., Kies, B., Rudzinska, M., Fine, J., Nikl, J., Honczarenko, K., et al. (2011) Rotigotine Effects on Early Morning Motor Function and Sleep in Parkinson’s Disease: A Double-Blind, Randomized, Placebo-Controlled Study (RECOVER). Movement Disorders, 26, 90-99.
https://doi.org/10.1002/mds.23441
[51] Pringsheim, T., Day, G.S., Smith, D.B., Rae-Grant, A., Licking, N., Armstrong, M.J., et al. (2021) Dopaminergic Therapy for Motor Symptoms in Early Parkinson Disease Practice Guideline Summary. Neurology, 97, 942-957.
https://doi.org/10.1212/wnl.0000000000012868
[52] Scanga, A., Lafontaine, A. and Kaminska, M. (2023) An Overview of the Effects of Levodopa and Dopaminergic Agonists on Sleep Disorders in Parkinson’s Disease. Journal of Clinical Sleep Medicine, 19, 1133-1144.
https://doi.org/10.5664/jcsm.10450
[53] Anderson, N. and Tran, P. (2025) Obstructive Sleep Apnea. Primary Care: Clinics in Office Practice, 52, 47-59.
https://doi.org/10.1016/j.pop.2024.09.007
[54] Iranzo, A. and Santamaría, J. (2005) Severe Obstructive Sleep Apnea/Hypopnea Mimicking REM Sleep Behavior Disorder. Sleep, 28, 203-206.
https://doi.org/10.1093/sleep/28.2.203
[55] Jo, S., Kim, H., Jeon, J.Y. and Lee, S. (2019) Protective Effects of REM Sleep without Atonia against Obstructive Sleep Apnea in Patients with Idiopathic REM Sleep Behavior Disorder. Sleep Medicine, 54, 116-120.
https://doi.org/10.1016/j.sleep.2018.10.032
[56] Kapur, V.K., Auckley, D.H., Chowdhuri, S., Kuhlmann, D.C., Mehra, R., Ramar, K., et al. (2017) Clinical Practice Guideline for Diagnostic Testing for Adult Obstructive Sleep Apnea: An American Academy of Sleep Medicine Clinical Practice Guideline. Journal of Clinical Sleep Medicine, 13, 479-504.
https://doi.org/10.5664/jcsm.6506
[57] Rundo, J.V. and Downey, R. (2019) Polysomnography. Handbook of Clinical Neurology, 160, 381-392.
[58] Neikrug, A.B., Liu, L., Avanzino, J.A., Maglione, J.E., Natarajan, L., Bradley, L., et al. (2014) Continuous Positive Airway Pressure Improves Sleep and Daytime Sleepiness in Patients with Parkinson Disease and Sleep Apnea. Sleep, 37, 177-185.
https://doi.org/10.5665/sleep.3332
[59] Kaminska, M., Mery, V.P., Lafontaine, A., Robinson, A., Benedetti, A., Gros, P., et al. (2018) Change in Cognition and Other Non-Motor Symptoms with Obstructive Sleep Apnea Treatment in Parkinson Disease. Journal of Clinical Sleep Medicine, 14, 819-828.
https://doi.org/10.5664/jcsm.7114
[60] Rotty, M.C., Suehs, C.M., Mallet, J.P., Martinez, C., Borel, J., Rabec, C., et al. (2021) Mask Side-Effects in Long-Term CPAP-Patients Impact Adherence and Sleepiness: The Interfacevent Real-Life Study. Respiratory Research, 22, Article No. 17.
https://doi.org/10.1186/s12931-021-01618-x
[61] Chaidas, K., Lamprou, K., Munnings, A., Stradling, J.R. and Nickol, A.H. (2022) Nasal Symptoms in Patients with Obstructive Sleep Apnoea and Their Association with Continuous Positive Airway Pressure Usage. Life, 12, Article 305.
https://doi.org/10.3390/life12020305
[62] Ramar, K., Dort, L.C., Katz, S.G., Lettieri, C.J., Harrod, C.G., Thomas, S.M., et al. (2015) Clinical Practice Guideline for the Treatment of Obstructive Sleep Apnea and Snoring with Oral Appliance Therapy: An Update for 2015. Journal of Dental Sleep Medicine, 11, 773-827.
https://doi.org/10.15331/jdsm.4868
[63] Castel, M., Cochen De Cock, V., Léon, H. and Dupuy-Bonafé, I. (2020) Mandibular Advancement Device in Parkinson’s Disease: A Pilot Study on Efficacy and Usability. Sleep Medicine, 66, 78-81.
https://doi.org/10.1016/j.sleep.2019.08.010
[64] Hudgel, D.W., Patel, S.R., Ahasic, A.M., Bartlett, S.J., Bessesen, D.H., Coaker, M.A., et al. (2018) The Role of Weight Management in the Treatment of Adult Obstructive Sleep Apnea. an Official American Thoracic Society Clinical Practice Guideline. American Journal of Respiratory and Critical Care Medicine, 198, e70-e87.
https://doi.org/10.1164/rccm.201807-1326st

为你推荐