Research Progress on Neural Mechanisms and Intervention Strategies of Cognitive Impairment Associated with Obstructive Sleep Apnea
DOI:
https://doi.org/10.71204/zkb2g519Keywords:
Obstructive Sleep Apnea, Cognitive Impairment, Glymphatic System, Dynamic Brain Functional Networks, Non-invasive Neuromodulation, Continuous Positive Airway PressureAbstract
Obstructive sleep apnea (OSA) is a prevalent sleep-related breathing disorder that is closely associated with cognitive impairment. However, the efficacy of conventional interventions remains limited, and exploring its neural mechanisms and adjunctive therapeutic strategies has become a research hotspot. This paper provides a narrative review of the research progress in neuroimaging mechanisms and intervention strategies for OSA-related cognitive impairment. Regarding neural mechanisms, this article focuses on two core mechanisms: dysfunction of the glymphatic system and unstable alterations in dynamic brain functional networks. Multimodal neuroimaging evidence demonstrates that patients with OSA exhibit distinct glymphatic system impairment and compromised dynamic reorganization ability of brain functional networks, characterized by "excessive persistence" and "abnormal transitions" of functional connectivity states. Pivotal mediation analyses have revealed for the first time the causal pathway of "glymphatic dysfunction → decreased brain network efficiency → cognitive impairment." In terms of intervention strategies, this article points out that continuous positive airway pressure (CPAP) has limited efficacy in improving cognitive function, accompanied by poor patient adherence. Non-invasive neuromodulation techniques represented by repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) show potential as adjunctive interventions due to their direct regulation of cortical excitability and neuroplasticity. Current research is limited by predominant cross-sectional designs, lack of standardized imaging biomarkers, and small sample sizes in intervention studies. Future research should focus on developing predictive models based on multimodal radiomics and artificial intelligence, exploring physical interventions targeting the glymphatic system, and conducting long-term randomized controlled trials enriched with biomarkers. This review aims to provide theoretical evidence and novel insights for the early identification and precise intervention of OSA-related cognitive impairment.
References
Allen, E. A., Damaraju, E., Plis, S. M., et al. (2014). Tracking whole-brain connectivity dynamics in the resting state. Cerebral Cortex, 24(3), 663–676.
Begemann, M. J., Brand, B. A., Ćurčić-Blake, B., et al. (2020). Efficacy of non-invasive brain stimulation on cognitive functioning in brain disorders: A meta-analysis. Psychological Medicine, 50(15), 2465–2486.
Benjafield, A. V., Ayas, N. T., Eastwood, P. R., et al. (2019). Estimation of the global prevalence and burden of obstructive sleep apnoea: A literature-based analysis. The Lancet Respiratory Medicine, 7(8), 687–698.
Benveniste, H., Liu, X., Koundal, S., et al. (2019). The glymphatic system and waste clearance with brain aging: A review. Gerontology, 65(2), 106–119.
Bradley, T. D., & Floras, J. S. (2009). Obstructive sleep apnoea and its cardiovascular consequences. The Lancet, 373(9657), 82–93.
Calhoun, V. D., Miller, R., Pearlson, G., et al. (2014). The chronnectome: Time-varying connectivity networks as the next frontier in fMRI data discovery. Neuron, 84(2), 262–274.
Coughlin, S. R., Mawdsley, L., Mugarza, J. A., et al. (2004). Obstructive sleep apnoea is independently associated with an increased prevalence of metabolic syndrome. European Heart Journal, 25(9), 735–741.
De la Herrán-Arita, A. K. (2026). When sleep fails, brain clearance suffers: The role of glymphatic impairment in clinical neurology. Acta Neurologica Belgica, 126(3), 783–792.
https://doi.org/10.1007/s13760-025-02959-w
Durtette, A., Dargent, B., Gierski, F., et al. (2024). Impact of continuous positive airway pressure on cognitive functions in adult patients with obstructive sleep apnea: A systematic review and meta-analysis. Sleep Medicine, 123, 7–21.
Frias, C. L., Almeria, M., Castejon, J., Artero, C., Caruana, G., Elias-Mas, A., Uscamaita, K., Hawkins, V., Ray, N. J., Buongiorno, M., Cullell, N., & Krupinski, J. (2025). A pilot study: The effect of CPAP intervention on sleep architecture and cognition in Alzheimer's disease patients with obstructive sleep apnea. Neurology International, 17(9), Article 147. https://doi.org/10.3390/neurolint17090147
Ghaderi, S., Mohammadi, S., & Fatehi, F. (2025). Glymphatic pathway dysfunction in severe obstructive sleep apnea: A meta-analysis. Sleep Medicine, 131, 106528.
Greenstone, M., & Hack, M. (2014). Obstructive sleep apnoea. BMJ, 348, g3745.
Guidelines for the diagnosis and treatment of obstructive sleep apnea hypopnea syndrome (revised 2011). (2012). In Proceedings of the 4th Northeast China Academic Conference on Respiratory Diseases & the 11th Annual Conference of Jilin Society of Respiratory Diseases (pp. 67–70).
Gurbani, N., Naismith, S., Rosenzweig, I., et al. (2025). Should we treat sleep apnoea to prevent dementia? Current Treatment Options in Neurology, 27(1), 26.
Han, X., Cai, S., Gui, H., et al. (2023). Transcranial magnetic stimulation cortical oscillations and improve cognition in obstructive sleep apnea patients. Brain and Behavior, 13(4), e2958.
Hassan Mohmmed Ahmed, A. F., Emam Mohamed Ahmed, N. M. A., Abdulwahid Elsamany, A. A., et al. (2025). The role of sleep disturbances in Alzheimer's disease progression: A systematic review. Cureus, 17(6), e86450.
He, Z., & Sun, J. (2025). Clearance mechanisms of the glymphatic/lymphatic system in the brain: New therapeutic perspectives for cognitive impairment. Cognitive Neurodynamics, 19(1), 111.
Huang, Y., Shen, C., Zhao, W., et al. (2023). Multilayer network analysis of dynamic network reconfiguration in patients with moderate-to-severe obstructive sleep apnea and its association with neurocognitive function. Sleep Medicine, 112, 333–341.
Jackson, M. L., & Rosenzweig, I. (2025). Perivascular dynamics, sleep apnea, and memory: Interpreting a moving target. American Journal of Respiratory and Critical Care Medicine, 211(12), 2244–2246.
Keil, S. A., Li, Y., Krieger, A. C., et al. (2026). Increased MRI-derived parenchymal cerebral spinal fluid mapping in untreated obstructive sleep apnea patients. Neurobiology of Disease, 221, 107325.
Lal, C., Ayappa, I., Ayas, N., et al. (2022). The link between obstructive sleep apnea and neurocognitive impairment: An official American thoracic society workshop report. Annals of the American Thoracic Society, 19(8), 1245–1256.
Li, H., Li, L., Li, K., et al. (2022). Abnormal dynamic functional network connectivity in male obstructive sleep apnea with mild cognitive impairment: A data-driven functional magnetic resonance imaging study. Frontiers in Aging Neuroscience, 14, 977917.
Li, Y., Lin, S., Guo, Z., et al. (2025). Decoupling of global signal and cerebrospinal fluid inflow is associated with cognitive decline in patients with obstructive sleep apnoea. Sleep Medicine, 129, 330–338.
Liu, G., Yang, C., Wang, X., et al. (2023). Oxygen metabolism abnormality and Alzheimer's disease: An update. Redox Biology, 68, 102955.
Ma, L., Liu, N., Feng, Y., et al. (2026). Exploration of plasma biomarkers of neurodegeneration in obstructive sleep apnea-related mild cognitive impairment. Clinical Otolaryngology, 51(1), 92–100.
Mayo Clinic. (n.d.). A study of automated manual lymphatic drainage therapy for obstructive sleep apnea. https://www.mayo.edu/research/clinical-trials/cls-20597241
Nepozitek, J., Marecek, S., Rottova, V., 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(1), 160.
Niu, Y., Sun, S., Wang, Y., et al. (2025). Spatiotemporal trends in the prevalence of obstructive sleep apnoea across China: A multilevel meta-analysis incorporating geographic and demographic stratification (2000-2024). Nature and Science of Sleep, 17, 879–903.
Preti, M. G., Bolton, T. A., & Van De Ville, D. (2017). The dynamic functional connectome: State-of-the-art and perspectives. NeuroImage, 160, 41–54.
Rektorová, I., Pupíková, M., Fleury, L., et al. (2025). Non-invasive brain stimulation: Current and future applications in neurology. Nature Reviews Neurology, 21(12), 669–686.
Ren, Y., Chen, S., Wang, H., et al. (2025). Unraveling the bidirectional links between obstructive sleep apnea and mild cognitive impairment: A systematic review and meta-analysis. Sleep Medicine, 132, 106562.
Rosenzweig, I., Glasser, M., Polsek, D., et al. (2015). Sleep apnoea and the brain: A complex relationship. The Lancet Respiratory Medicine, 3(5), 404–414.
Rotenberg, B. W., Murariu, D., & Pang, K. P. (2016). Trends in CPAP adherence over twenty years of data collection: A flattened curve. Journal of Otolaryngology - Head & Neck Surgery, 45(1), 43.
Sawyer, A. M., Gooneratne, N. S., Marcus, C. L., et al. (2011). A systematic review of CPAP adherence across age groups: Clinical and empiric insights for developing CPAP adherence interventions. Sleep Medicine Reviews, 15(6), 343–356.
Sheikh Ibrahim, H. (2025). SBAV: A sex-stratified precision framework for predicting sleep apnea–driven neurodegeneration in aging women [Conference abstract]. Innovation in Aging, 9(Suppl. 2), igaf122.4257. https://doi.org/10.1093/geroni/igaf122.4257
Shine, J. M., Bissett, P. G., Bell, P. T., et al. (2016). The dynamics of functional brain networks: Integrated network states during cognitive task performance. Neuron, 92(2), 544–554.
Sommer, R., Hill, E. A., Ramirez, J., et al. (2025). Continuous positive airway pressure and progression of enlarged perivascular spaces in adults with obstructive sleep apnea. Neurology, 105(8), e213955.
Wang, J., Wang, Z., Wang, X., et al. (2025). Altered brain dynamic functional connectivity in patients with obstructive sleep apnea and its association with cognitive performance. Sleep Medicine, 128, 174–182.
Wostyn, P., & Nedergaard, M. (2026). Ocular glymphatic dysfunction as a potential link between obstructive sleep apnea and retinal structural changes. Comment on Pusic Sesar et al. Multimodal assessment of ocular parameters in patients with severe obstructive sleep apnea with emphasis on retinal structural changes. Life 2025, 15, 1307. Life, 16(2), Article 214. https://doi.org/10.3390/life16020214
Wu, M., Song, W., Wang, X., et al. (2025). Efficacy of non-invasive brain stimulation interventions on cognitive impairment: An umbrella review of meta-analyses of randomized controlled trials. Journal of NeuroEngineering and Rehabilitation, 22(1), 22.
Xiong, Z., Bai, M., Wang, Z., et al. (2024). Resting-state fMRI network efficiency as a mediator in the relationship between the glymphatic system and cognitive function in obstructive sleep apnea hypopnea syndrome: Insights from a DTI-ALPS investigation. Sleep Medicine, 119, 250–257.
Yankova, G., Bogomyakova, O., & Tulupov, A. (2021). The glymphatic system and meningeal lymphatics of the brain: New understanding of brain clearance. Reviews in the Neurosciences, 32(7), 693–705.
Yao, L., Wang, Y., Gao, Y., Gao, H., & Guo, X. (2023). The role of the fronto-parietal network in modulating sustained attention under sleep deprivation: An functional magnetic resonance imaging study. Frontiers in Psychiatry, 14, Article 1289300. https://doi.org/10.3389/fpsyt.2023.1289300
Yi, H. J., Liao, X. Y., Pi, M. Y., et al. (2023). Establishment of a new telemedicine-based model for the diagnosis and treatment of obstructive sleep apnea: Study protocol for a non-inferiority randomized controlled trial. Chinese General Practice, 26(3), 380–385.
Yu, R., Li, Y., Zhao, K., et al. (2025). The contributions of resting-state functional-MRI studies to our understanding of male patients with obstructive sleep apnea: A systematic review. Frontiers in Neurology, 16, 1532037.
Yu, S., Wang, S., & Sun, H. (2024). Effects of repetitive transcranial magnetic stimulation on inhibitory control in first-episode schizophrenia: Behavioral and neural mechanisms. Frontiers in Psychiatry, 15, Article 1496562. https://doi.org/10.3389/fpsyt.2024.1496562
Zalesky, A., Fornito, A., Cocchi, L., et al. (2014). Time-resolved resting-state brain networks. Proceedings of the National Academy of Sciences of the United States of America, 111(28), 10341–10346.
Zhang, X., Xu, H., Yin, S., et al. (2025). Obstructive sleep apnea and memory impairments: Clinical characterization, treatment strategies, and mechanisms. Sleep Medicine Reviews, 81, 102092.
Zhao, X., Liu, J., Shao, Z., Liu, X., Wang, Z., Yuan, K., Zhang, B., Li, Y., Sheng, X., Zhu, Y., & Guo, Y. (2024). Restoration of abnormal sleep EEG power in patients with insomnia disorder after 1Hz rTMS over left DLPFC. Frontiers in Psychiatry, 15, Article 1431837. https://doi.org/10.3389/fpsyt.2024.1431837
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Copyright (c) 2026 Yejun Du, Weikai Zhang, Zhanfeng Yan (Author)
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