睡眠障碍与脑小血管病的研究进展
Research Progress on Sleep Disorders and Cerebral Small Vessel Disease
DOI: 10.12677/jcpm.2026.52140, PDF,   
作者: 王 楠：内蒙古自治区精神卫生中心(内蒙古自治区第三医院、内蒙古自治区脑科医院)，神经内二科，内蒙古 呼和浩特
关键词: 脑小血管病；睡眠障碍；Cerebral Small Vessel Disease； Sleep Disorders
摘要: 近年来，随着影像学技术的革新与人口老龄化趋势，脑小血管病(CSVD)相关性研究的重要性日益凸显。作为老年人群认知功能损害的重要血管性病因，该疾病已成为当前神经病学研究的重要方向。最新循证医学证据揭示，CSVD与睡眠障碍存在显著的病理生理学关联，二者相互影响的机制研究正成为研究热点。本文通过整合分析国内外最新研究成果，深入探讨这两种疾病的相互作用模式，以期为基础研究和临床干预提供新的思路。
Abstract: In recent years, with the innovation of imaging techniques and the trend of population aging, the importance of research on the correlation of cerebral small vessel disease (CSVD) has become increasingly prominent. As an important vascular cause of cognitive impairment in the elderly population, this disease has become an important direction in current neurology research. The latest evidence-based medical evidence reveals that there is a significant pathophysiological association between CSVD and sleep disorders, and the research on the mechanism of their mutual influence is becoming a research hotspot. This article, by integrating and analyzing the latest research achievements at home and abroad, deeply explores the interaction patterns of these two diseases, with the aim of providing new ideas for basic research and clinical intervention.
文章引用：王楠. 睡眠障碍与脑小血管病的研究进展[J]. 临床个性化医学, 2026, 5(2): 405-412. https://doi.org/10.12677/jcpm.2026.52140

参考文献

[1] Zhang, D., Cao, Y., Mu, J., Liu, Y., Gao, F., Han, F., et al. (2022) Inflammatory Biomarkers and Cerebral Small Vessel Disease: A Community-Based Cohort Study. Stroke and Vascular Neurology, 7, 302-309. [Google Scholar] [CrossRef] [PubMed]
[2] Wu, B., Liu, F., Sun, G. and Wang, S. (2023) Correlation between Obstructive Sleep Apnea and Cerebral Small Vessel Disease: A Mendelian Randomization Study. Genes & Genomics, 45, 1179-1186. [Google Scholar] [CrossRef] [PubMed]
[3] Kepplinger, J., Barlinn, K., Boehme, A.K., Gerber, J., Puetz, V., Pallesen, L., et al. (2013) Association of Sleep Apnea with Clinically Silent Microvascular Brain Tissue Changes in Acute Cerebral Ischemia. Journal of Neurology, 261, 343-349. [Google Scholar] [CrossRef] [PubMed]
[4] Chen, X., Wang, J., Shan, Y., Cai, W., Liu, S., Hu, M., et al. (2018) Cerebral Small Vessel Disease: Neuroimaging Markers and Clinical Implication. Journal of Neurology, 266, 2347-2362. [Google Scholar] [CrossRef] [PubMed]
[5] Ge, L., Guyatt, G., Tian, J., Pan, B., Chang, Y., Chen, Y., et al. (2019) Insomnia and Risk of Mortality from All-Cause, Cardiovascular Disease, and Cancer: Systematic Review and Meta-Analysis of Prospective Cohort Studies. Sleep Medicine Reviews, 48, Article ID: 101215. [Google Scholar] [CrossRef] [PubMed]
[6] Li, L., Gan, Y., Zhou, X., Jiang, H., Zhao, Y., Tian, Q., et al. (2021) Insomnia and the Risk of Hypertension: A Meta-Analysis of Prospective Cohort Studies. Sleep Medicine Reviews, 56, Article ID: 101403. [Google Scholar] [CrossRef] [PubMed]
[7] Hertenstein, E., Feige, B., Gmeiner, T., Kienzler, C., Spiegelhalder, K., Johann, A., et al. (2019) Insomnia as a Predictor of Mental Disorders: A Systematic Review and Meta-Analysis. Sleep Medicine Reviews, 43, 96-105. [Google Scholar] [CrossRef] [PubMed]
[8] 汤永红, 李敏. 睡眠障碍研究进展[J]. 中神经免疫学和神经病杂志, 2024, 31(6): 423-428
[9] Bertisch, S.M., Pollock, B.D., Mittleman, M.A., Buysse, D.J., Bazzano, L.A., Gottlieb, D.J., et al. (2018) Insomnia with Objective Short Sleep Duration and Risk of Incident Cardiovascular Disease and All-Cause Mortality: Sleep Heart Health Study. Sleep, 41. [Google Scholar] [CrossRef] [PubMed]
[10] Wang, J., Chen, X., Men, X., Chen, M., Tao, J. and Lu, Z. (2020) Chronic Insomnia Is Associated with Higher Circulating Interleukin-8 in Patients with Atherosclerotic Cerebral Small Vessel Disease. Nature and Science of Sleep, 12, 93-99. [Google Scholar] [CrossRef] [PubMed]
[11] Devine, J.K., Bertisch, S.M., Yang, H., Scott-Sutherland, J., Wilkins, A., Molina, V., et al. (2019) Glucocorticoid and Inflammatory Reactivity to a Repeated Physiological Stressor in Insomnia Disorder. Neurobiology of Sleep and Circadian Rhythms, 6, 77-84. [Google Scholar] [CrossRef] [PubMed]
[12] Grimaldi, D., Reid, K.J., Papalambros, N.A., Braun, R.I., Malkani, R.G., Abbott, S.M., et al. (2020) Autonomic Dysregulation and Sleep Homeostasis in Insomnia. Sleep, 44, zsaa274. [Google Scholar] [CrossRef] [PubMed]
[13] Irwin, M.R. (2019) Sleep and Inflammation: Partners in Sickness and in Health. Nature Reviews Immunology, 19, 702-715. [Google Scholar] [CrossRef] [PubMed]
[14] Irwin, M.R., Olmstead, R. and Carroll, J.E. (2016) Sleep Disturbance, Sleep Duration, and Inflammation: A Systematic Review and Meta-Analysis of Cohort Studies and Experimental Sleep Deprivation. Biological Psychiatry, 80, 40-52. [Google Scholar] [CrossRef] [PubMed]
[15] Yu, C., Lu, W., Qiu, J., Wang, F., Li, J. and Wang, L. (2020) Alterations of the Whole Cerebral Blood Flow in Patients with Different Total Cerebral Small Vessel Disease Burden. Frontiers in Aging Neuroscience, 12, Article 175. [Google Scholar] [CrossRef] [PubMed]
[16] del Rey, A. and Besedovsky, H.O. (2017) Immune-neuro-endocrine Reflexes, Circuits, and Networks: Physiologic and Evolutionary Implications. In: Savino, W. and Guaraldi, F., Eds., Frontiers of Hormone Research, S. Karger AG, 1-18. [Google Scholar] [CrossRef] [PubMed]
[17] Rochfort, K.D. and Cummins, P.M. (2015) Cytokine-mediated Dysregulation of Zonula Occludens-1 Properties in Human Brain Microvascular Endothelium. Microvascular Research, 100, 48-53. [Google Scholar] [CrossRef] [PubMed]
[18] Tikhomirova, O.V., Kozhevnikova, V.V., Zybina, N.N., Startseva, O.N. and Bobko, O.V. (2018) A Role of Insomnia in the Development of Silent Cerebral Infarctions. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova, 118, 3-7. [Google Scholar] [CrossRef] [PubMed]
[19] Rostampour, M., Gharaylou, Z., Rostampour, N., Kaveh, D., Noori, K., Fadaei, R., et al. (2021) Asymmetric Alterations of White Matter Integrity in Patients with Insomnia Disorder. Brain Imaging and Behavior, 16, 389-396. [Google Scholar] [CrossRef] [PubMed]
[20] Kang, J.M., Joo, S.W., Son, Y., Kim, H., Ko, K., Lee, J.S., et al. (2018) Low White-Matter Integrity between the Left Thalamus and Inferior Frontal Gyrus in Patients with Insomnia Disorder. Journal of Psychiatry and Neuroscience, 43, 366-374. [Google Scholar] [CrossRef] [PubMed]
[21] Lu, F., Dai, J., Couto, T.A., Liu, C., Chen, H., Lu, S., et al. (2017) Diffusion Tensor Imaging Tractography Reveals Disrupted White Matter Structural Connectivity Network in Healthy Adults with Insomnia Symptoms. Frontiers in Human Neuroscience, 11, Article 583. [Google Scholar] [CrossRef] [PubMed]
[22] Lloret, M., Cervera-Ferri, A., Nepomuceno, M., Monllor, P., Esteve, D. and Lloret, A. (2020) Is Sleep Disruption a Cause or Consequence of Alzheimer’s Disease? Reviewing Its Possible Role as a Biomarker. International Journal of Molecular Sciences, 21, Article 1168. [Google Scholar] [CrossRef] [PubMed]
[23] Seiler, A., Camilo, M., Korostovtseva, L., Haynes, A.G., Brill, A., Horvath, T., et al. (2019) Prevalence of Sleep-Disordered Breathing after Stroke and TIA. Neurology, 92, e648-e654. [Google Scholar] [CrossRef] [PubMed]
[24] Del Brutto, O.H., Mera, R.M., Zambrano, M. and Castillo, P.R. (2017) Relationship between Obstructive Sleep Apnea and Neuroimaging Signatures of Cerebral Small Vessel Disease in Community-Dwelling Older Adults. the Atahualpa Project. Sleep Medicine, 37, 10-12. [Google Scholar] [CrossRef] [PubMed]
[25] Huang, Y., Yang, C., Yuan, R., Liu, M. and Hao, Z. (2019) Association of Obstructive Sleep Apnea and Cerebral Small Vessel Disease: A Systematic Review and Meta-Analysis. Sleep, 43, zsz264. [Google Scholar] [CrossRef] [PubMed]
[26] Park, K.M., Wi, J. and Kim, J. (2024) The Association between Small Vessel Disease and Obstructive Sleep Apnea: A Peak Width of Skeletonized Mean Diffusivity-Based Study. Sleep and Breathing, 29, Article No. 29. [Google Scholar] [CrossRef] [PubMed]
[27] Ho, B., Tseng, P., Lai, C., Wu, M., Tsai, M., Hsieh, C., et al. (2018) Obstructive Sleep Apnea and Cerebral White Matter Change: A Systematic Review and Meta-Analysis. Journal of Neurology, 265, 1643-1653. [Google Scholar] [CrossRef] [PubMed]
[28] Huang, S., Wang, D., Zhou, H., Chen, Z., Wang, H., Li, Y., et al. (2019) Neuroimaging Consequences of Cerebral Small Vessel Disease in Patients with Obstructive Sleep Apnea-Hypopnea Syndrome. Brain and Behavior, 9, e01364. [Google Scholar] [CrossRef] [PubMed]
[29] Gregori-Pla, C., Zirak, P., Cotta, G., Bramon, P., Blanco, I., Serra, I., et al. (2023) How Does Obstructive Sleep Apnea Alter Cerebral Hemodynamics? SLEEP, 46, zsad122. [Google Scholar] [CrossRef] [PubMed]
[30] Wang, J., Yu, W., Gao, M., Zhang, F., Gu, C., Yu, Y., et al. (2015) Impact of Obstructive Sleep Apnea Syndrome on Endothelial Function, Arterial Stiffening, and Serum Inflammatory Markers: An Updated Meta‐analysis and Metaregression of 18 Studies. Journal of the American Heart Association, 4, e002454. [Google Scholar] [CrossRef] [PubMed]
[31] Lloret, A., Esteve, D., Lloret, M.A., Monllor, P., López, B., León, J.L., et al. (2021) Is Oxidative Stress the Link between Cerebral Small Vessel Disease, Sleep Disruption, and Oligodendrocyte Dysfunction in the Onset of Alzheimer’s Disease? Frontiers in Physiology, 12, Article 708061. [Google Scholar] [CrossRef] [PubMed]
[32] Backhouse, E.V., McHutchison, C.A., Cvoro, V., Shenkin, S.D. and Wardlaw, J.M. (2017) Early Life Risk Factors for Cerebrovascular Disease: A Systematic Review and Meta-Analysis. Neurology, 88, 976-984. [Google Scholar] [CrossRef] [PubMed]
[33] Rajani, R.M., Quick, S., Ruigrok, S.R., Graham, D., Harris, S.E., Verhaaren, B.F.J., et al. (2018) Reversal of Endothelial Dysfunction Reduces White Matter Vulnerability in Cerebral Small Vessel Disease in Rats. Science Translational Medicine, 10, eaam9507. [Google Scholar] [CrossRef] [PubMed]
[34] Robbins, J., Redline, S., Ervin, A., Walsleben, J.A., Ding, J. and Nieto, F.J. (2005) Associations of Sleep-Disordered Breathing and Cerebral Changes on Mri. Journal of Clinical Sleep Medicine, 1, 159-165. [Google Scholar] [CrossRef] 
[35] Duning, T., Deppe, M., Brand, E., Stypmann, J., Becht, C., Heidbreder, A., et al. (2013) Brainstem Involvement as a Cause of Central Sleep Apnea: Pattern of Microstructural Cerebral Damage in Patients with Cerebral Microangiopathy. PLOS ONE, 8, e60304. [Google Scholar] [CrossRef] [PubMed]
[36] Spektor, E., Fietze, I. and Poluektov, M.G. (2021) Periodic Limb Movements Syndrome in Patients with Cerebral Small Vessel Disease: Protocol for a Prospective Observational Study. Frontiers in Neurology, 12, Article 700151. [Google Scholar] [CrossRef] [PubMed]
[37] Stefani, A. and Högl, B. (2019) Diagnostic Criteria, Differential Diagnosis, and Treatment of Minor Motor Activity and Less Well-Known Movement Disorders of Sleep. Current Treatment Options in Neurology, 21, Article No. 1. [Google Scholar] [CrossRef] [PubMed]
[38] Boulos, M.I., Murray, B.J., Muir, R.T., Gao, F., Szilagyi, G.M., Huroy, M., et al. (2016) Periodic Limb Movements and White Matter Hyperintensities in First-Ever Minor Stroke or High-Risk Transient Ischemic Attack. Sleep, 40, zsw080. [Google Scholar] [CrossRef] [PubMed]
[39] Manconi, M., Bassetti, C.L. and Ferri, R. (2017) Periodic Limb Movements during Sleep and White Matter MRI Hyperintensity in Minor Stroke or Tia. Sleep, 40, zsx031. [Google Scholar] [CrossRef] [PubMed]
[40] Kang, M.K., Koo, D.L., Shin, J.H., Kwon, H. and Nam, H. (2018) Association between Periodic Limb Movements during Sleep and Cerebral Small Vessel Disease. Sleep Medicine, 51, 47-52. [Google Scholar] [CrossRef] [PubMed]
[41] Del Brutto, O.H., Mera, R.M., Del Brutto, V.J. and Castillo, P.R. (2020) Lack of Association between Periodic Limb Movements during Sleep and Neuroimaging Signatures of Cerebral Small Vessel Disease in Stroke-Free Community-Dwelling Older Adults. the Atahualpa Project. Journal of Stroke and Cerebrovascular Diseases, 29, Article ID: 104497. [Google Scholar] [CrossRef] [PubMed]
[42] Ouyang, F., Wang, M., Liao, M., Lan, L., Liu, X., Li, H., et al. (2022) Association between Periodic Limb Movements during Sleep and Neuroimaging Features of Cerebral Small Vessel Disease: A Preliminary Cross‐Sectional Study. Journal of Sleep Research, 31, e13573. [Google Scholar] [CrossRef] [PubMed]
[43] Ferri, R., Cosentino, F.I.I., Moussouttas, M., Lanuzza, B., Aricò, D., Bagai, K., et al. (2016) Silent Cerebral Small Vessel Disease in Restless Legs Syndrome. Sleep, 39, 1371-1377. [Google Scholar] [CrossRef] [PubMed]
[44] Cho, Y.W., Kim, K.T., Lee, Y.S., Moon, H., Chang, H., Ku, J., et al. (2016) White Matter Hyperintensities on Brain Magnetic Resonance Imaging: Comparison of Early-Onset and Late-Onset Restless Legs Syndrome. Sleep Medicine, 25, 4-7. [Google Scholar] [CrossRef] [PubMed]
[45] Zhao, J., Kong, Q., Wang, M., Huang, H., Zhou, X., Guo, Y., et al. (2022) Association of Excessive Daytime Sleepiness with Cerebral Small Vessel Disease in Community-Dwelling Older Adults. Nature and Science of Sleep, 14, 765-773. [Google Scholar] [CrossRef] [PubMed]
[46] Li, J., Vitiello, M.V. and Gooneratne, N.S. (2018) Sleep in Normal Aging. Sleep Medicine Clinics, 13, 1-11. [Google Scholar] [CrossRef] [PubMed]
[47] Wang, J., Chen, X., Liao, J., Zhou, L., Han, H., Tao, J., et al. (2020) Non Breathing-Related Sleep Fragmentation and Imaging Markers in Patients with Atherosclerotic Cerebral Small Vessel Disease (CSVD): A Cross-Sectional Case-Control Study. BMC Neurology, 20, Article No. 98. [Google Scholar] [CrossRef] [PubMed]
[48] Bellesi, M., Pfister-Genskow, M., Maret, S., Keles, S., Tononi, G. and Cirelli, C. (2013) Effects of Sleep and Wake on Oligodendrocytes and Their Precursors. The Journal of Neuroscience, 33, 14288-14300. [Google Scholar] [CrossRef] [PubMed]
[49] Bellesi, M., Haswell, J.D., de Vivo, L., Marshall, W., Roseboom, P.H., Tononi, G., et al. (2018) Myelin Modifications after Chronic Sleep Loss in Adolescent Mice. Sleep, 41, zsy034. [Google Scholar] [CrossRef] [PubMed]
[50] de Vivo, L. and Bellesi, M. (2019) The Role of Sleep and Wakefulness in Myelin Plasticity. Glia, 67, 2142-2152. [Google Scholar] [CrossRef] [PubMed]
[51] Fu, X., Wan, X., Liu, J., Sun, Q., Shen, Y., Li, J., et al. (2023) Effects of Sleep Fragmentation on White Matter Pathology in a Rat Model of Cerebral Small Vessel Disease. Sleep, 47, zsad225. [Google Scholar] [CrossRef] [PubMed]