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Advances in MRI of the glymphatic system in cognitive impairment diseases
YANG Siyi  XIANG Yu  NIU Zhihao  LI Shiguang 

Cite this article as: YANG S Y, XIANG Y, NIU Z H, et al. Advances in MRI of the glymphatic system in cognitive impairment diseases[J]. Chin J Magn Reson Imaging, 2026, 17(4): 114-120. DOI:10.12015/issn.1674-8034.2026.04.016.


[Abstract] Cognitive impairment diseases refer to a group of acquired disorders primarily characterized by cognitive dysfunction. The glymphatic system (GS), a newly discovered intracerebral metabolic waste clearance system in recent years, has been shown in numerous studies to be closely associated with various cognitive impairment diseases. Due to its multimodal imaging capabilities, MRI has been widely used in GS research and has become a key carrier for investigating GS, providing important evidence for exploring the mechanisms underlying cognitive impairment diseases. This article will briefly introduce the structure and function of the GS, review the MRI imaging techniques for GS along with their advantages and disadvantages, focus on the core theme of GS dysfunction, and systematically sort out its mechanism of action and application progress in various cognitive impairment diseases, while pointing out the limitations of current research and exploring future research directions, aiming to reveal the importance of GS dysfunction in neuroimaging research and support the diagnosis, treatment, and prognosis assessment of related diseases.
[Keywords] cognitive impairment diseases；glymphatic system；magnetic resonance imaging；neuroimaging

YANG Siyi1   XIANG Yu1   NIU Zhihao1   LI Shiguang1, 2*  

1 College of Medical Imaging, Guizhou Medical University, Guiyang 550004, China

2 Department of Imaging, the Second People's Hospital of Guiyang, Guiyang 550023, China

Corresponding author: LI S G, E-mail: imaging_shiguangli@163.com

Conflicts of interest   None.

Received  2026-01-17
Accepted  2026-03-12
DOI: 10.12015/issn.1674-8034.2026.04.016
Cite this article as: YANG S Y, XIANG Y, NIU Z H, et al. Advances in MRI of the glymphatic system in cognitive impairment diseases[J]. Chin J Magn Reson Imaging, 2026, 17(4): 114-120. DOI:10.12015/issn.1674-8034.2026.04.016.

[1]
Cognitive Disorders Branch of Chinese Geriatrics Society. Chinese expert consensus on genetic diagnosis strategies for cognitive impairment diseases (2025 edition)[J]. Chin J Geriatr, 2025, 44(9): 1212-1225. DOI: 10.3760/cma.j.issn.0254-9026.2025.09.002.
[2]
Chinese Expert Consensus Committee on Brain Cognitive Health Management, Chinese Journal of Health Management Editorial Committee. Chinese expert consensus on cognitive health management (2023)[J]. Chin J Health Manag, 2023, 17(12): 881-892. DOI: 10.3760/cma.j.cn115624-20230908-00124.
[3]
LYU J, WANG X, DUAN Q, et al. Progress in magnetic resonance imaging of the glymphatic system[J/OL]. Magn Reson Lett, 2024, 4(4): 200154 [2026-01-17]. https://pubmed.ncbi.nlm.nih.gov/40917472/. DOI: 10.1016/j.mrl.2024.200154.
[4]
PLOG B A, NEDERGAARD M. The Glymphatic System in Central Nervous System Health and Disease: Past, Present, and Future[J]. Annu Rev Pathol, 2018, 13: 379-394. DOI: 10.1146/annurev-pathol-051217-111018.
[5]
SHENTU W, KONG Q, ZHANG Y, et al. Functional abnormalities of the glymphatic system in cognitive disorders[J]. Neural Regen Res, 2025, 20(12): 3430-3447. DOI: 10.4103/NRR.NRR-D-24-01049.
[6]
VENKAT P, CHOPP M, ZACHAREK A, et al. White matter damage and glymphatic dysfunction in a model of vascular dementia in rats with no prior vascular pathologies[J]. Neurobiol Aging, 2017, 50: 96-106. DOI: 10.1016/j.neurobiolaging.2016.11.002.
[7]
LEE Y, CHOI Y, PARK E J, et al. Improvement of glymphatic-lymphatic drainage of beta-amyloid by focused ultrasound in Alzheimer's disease model[J/OL]. Sci Rep, 2020, 10(1): 16144 [2026-01-17]. https://pubmed.ncbi.nlm.nih.gov/32999351/. DOI: 10.1038/s41598-020-73151-8.
[8]
EIDE P K, RINGSTAD G. Delayed clearance of cerebrospinal fluid tracer from entorhinal cortex in idiopathic normal pressure hydrocephalus: A glymphatic magnetic resonance imaging study[J]. J Cerebr Blood F Met, 2019, 39(7): 1355-1368. DOI: 10.1177/0271678X18760974.
[9]
BUONGIORNO M, GRANELL E, CARUANA G, et al. Impairments in sleep and brain molecular clearance in people with cognitive deterioration and biological evidence of AD: a report of four cases[J/OL]. BMC Neurol, 2023, 23(1): 417 [2026-01-17]. https://pubmed.ncbi.nlm.nih.gov/37993780/. DOI: 10.1186/s12883-023-03460-8.
[10]
RINGSTAD G, VATNEHOL S A S, EIDE P K. GlymphaticMRIin idiopathic normal pressure hydrocephalus[J]. Brain, 2017, 140(10): 2691-2705. DOI: 10.1093/brain/awx191.
[11]
ZHANG M, TANG J, XIA D, et al. Evaluation of glymphatic-meningeal lymphatic system with intravenous gadolinium-based contrast-enhancement in cerebral small-vessel disease[J]. Eur Radiol, 2023, 33(9): 6096-6106. DOI: 10.1007/s00330-023-09796-6.
[12]
TAOKA T, MASUTANI Y, KAWAI H, et al. Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer's disease cases[J]. Jpn J Radiol, 2017, 35(4): 172-178. DOI: 10.1007/s11604-017-0617-z.
[13]
BAE Y J, CHOI B S, KIM J M, et al. Altered glymphatic system in idiopathic normal pressure hydrocephalus[J]. Parkinsonism Relat Disord, 2021, 82: 56-60. DOI: 10.1016/j.parkreldis.2020.11.009.
[14]
ROY B, NUNEZ A, AYSOLA R S, et al. Impaired Glymphatic System Actions in Obstructive Sleep Apnea Adults[J/OL]. Front Neurosci, 2022, 16: 884234 [2026-01-17]. https://pubmed.ncbi.nlm.nih.gov/35600625/. DOI: 10.3389/fnins.2022.884234.
[15]
RAMASWAMY S, KHASIYEV F, GUTIERREZ J. Brain Enlarged Perivascular Spaces as Imaging Biomarkers of Cerebrovascular Disease: A Clinical Narrative Review[J/OL]. J Am Heart Assoc, 2022, 11(24): e026601 [2026-01-17]. https://pubmed.ncbi.nlm.nih.gov/36533613/. DOI: 10.1161/JAHA.122.026601.
[16]
WAYMONT J M J, VALDÉS HERNÁNDEZ M D C, BERNAL J, et al. Systematic review and meta-analysis of automated methods for quantifying enlarged perivascular spaces in the brain[J/OL]. Neuroimage, 2024, 297: 120685 [2026-01-17]. https://pubmed.ncbi.nlm.nih.gov/38914212/. DOI: 10.1016/j.neuroimage.2024.120685.
[17]
YANG Y, WANG M, LUAN M, et al. Enlarged Perivascular Spaces and Age-Related Clinical Diseases[J]. Clin Interv Aging, 2023, 18: 855-867. DOI: 10.2147/CIA.S404908.
[18]
GARIC D, MCKINSTRY R C, RUTSOHN J, et al. Enlarged Perivascular Spaces in Infancy and Autism Diagnosis, Cerebrospinal Fluid Volume, and Later Sleep Problems[J/OL]. JAMA Netw Open, 2023, 6(12): e2348341 [2026-01-17]. https://pubmed.ncbi.nlm.nih.gov/38113043/. DOI: 10.1001/jamanetworkopen.2023.48341.
[19]
PARK S, PARK B S, LEE H J, et al. Choroid plexus enlargement in patients with end-stage renal disease: implications for glymphatic system dysfunction[J/OL]. Front Neurol, 2024, 15: 1459356 [2026-01-17]. https://pubmed.ncbi.nlm.nih.gov/39469069/. DOI: 10.3389/fneur.2024.1459356.
[20]
ORZYŁOWSKA A, OAKDEN W. Saturation TransferMRIfor Detection of Metabolic and Microstructural Impairments Underlying Neurodegeneration in Alzheimer's Disease[J/OL]. Brain Sci, 2021, 12(1): 53 [2026-01-17]. https://pubmed.ncbi.nlm.nih.gov/35053797/. DOI: 10.3390/brainsci12010053.
[21]
JOSEPH C R. Utilizing 3D Arterial Spin Labeling to Identify Cerebrovascular Leak and Glymphatic Obstruction in Neurodegenerative Disease[J/OL]. Diagnostics (Basel), 2021, 11(10): 1888 [2026-01-17]. https://pubmed.ncbi.nlm.nih.gov/34679586/. DOI: 10.3390/diagnostics11101888.
[22]
SHANG Y, YU L, XING H, et al. Diffusion Tensor Imaging Analysis Along the Perivascular Space (DTI-ALPS) Demonstrates That Sleep Disorders Exacerbate Glymphatic Circulatory Impairment and Cognitive Impairment in Patients with Alzheimer's Disease[J]. Nat Sci Sleep, 2024, 16: 2205-2215. DOI: 10.2147/NSS.S496607.
[23]
HSU J L, WEI Y C, TOH C H, et al. Magnetic Resonance Images Implicate That Glymphatic Alterations Mediate Cognitive Dysfunction in Alzheimer Disease[J]. Ann Neurol, 2023, 93(1): 164-174. DOI: 10.1002/ana.26516.
[24]
WEN C, GAN J H, LIU S, et al. Enlarged perivascular spaces correlate with blood-brain barrier leakage and cognitive impairment in Alzheimer's disease[J]. J Alzheimers Dis, 2025, 104(2): 382-392. DOI: 10.1177/13872877251317220.
[25]
REN L, YE J. Commentary: The central lymphatic drainage in pharmacological, surgical and physical therapies of Alzheimer's disease[J]. Acta Pharm Sin B, 2024, 14(7): 3291-3293. DOI: 10.1016/j.apsb.2024.04.018.
[26]
HE X, CHEN L, WANG W C. Research progress in central nervous system diseases and the brain lymphatic system[J]. Chin J Magn Reson Imaging, 2025, 16(3): 127-132. DOI: 10.12015/issn.1674-8034.2025.03.021.
[27]
HOSHI A, TSUNODA A, TADA M, et al. Expression of Aquaporin 1 and Aquaporin 4 in the Temporal Neocortex of Patients with Parkinson's Disease[J]. Brain Pathol, 2017, 27(2): 160-168. DOI: 10.1111/bpa.12369.
[28]
ZHAO Y, XU C, CHEN Y, et al. Glymphatic dysfunction exacerbates cognitive decline by triggering cortical degeneration in Parkinson's disease: evidence from diffusion-tensor MRI[J/OL]. Brain Commun, 2025, 7(1): fcaf029 [2026-01-17]. https://pubmed.ncbi.nlm.nih.gov/39980740/. DOI: 10.1093/braincomms/fcaf029.
[29]
GUI Q, MENG J, SHEN M, et al. Relationship of Glymphatic Function with Cognitive Impairment, Sleep Disorders, Anxiety and Depression in Patients with Parkinson's Disease[J]. Neuropsychiatr Dis Treat, 2024, 20: 1809-1821. DOI: 10.2147/NDT.S480183.
[30]
SOLDOZY S, YAĞMURLU K, KUMAR J, et al. Interplay between vascular hemodynamics and the glymphatic system in the pathogenesis of idiopathic normal pressure hydrocephalus, exploring novel neuroimaging diagnostics[J]. Neurosurg Rev, 2022, 45(2): 1255-1261. DOI: 10.1007/s10143-021-01690-3.
[31]
KIKUTA J, KAMAGATA K, TAOKA T, et al. Water Diffusivity Changes Along the Perivascular Space After Lumboperitoneal Shunt Surgery in Idiopathic Normal Pressure Hydrocephalus[J/OL]. Front Neurol, 2022, 13: 843883 [2026-01-17]. https://pubmed.ncbi.nlm.nih.gov/35295837/. DOI: 10.3389/fneur.2022.843883.
[32]
PHILIPS T, BENTO-ABREU A, NONNEMAN A, et al. Oligodendrocyte dysfunction in the pathogenesis of amyotrophic lateral sclerosis[J]. Brain, 2013, 136(Pt 2): 471-482. DOI: 10.1093/brain/aws339.
[33]
LIU S, SUN X, REN Q, et al. Glymphatic dysfunction in patients with early-stage amyotrophic lateral sclerosis[J]. Brain, 2024, 147(1): 100-108. DOI: 10.1093/brain/awad274.
[34]
MCMILLAN M, GOMEZ N, HSIEH C, et al. RNA methylation influences TDP43 binding and disease pathogenesis in models of amyotrophic lateral sclerosis and frontotemporal dementia[J/OL]. Mol Cell, 2023, 83(2): 219-236.e7 [2026-01-17]. https://pubmed.ncbi.nlm.nih.gov/36634675/. DOI: 10.1016/j.molcel.2022.12.019.
[35]
JIANG D, LIU L, KONG Y, et al. Regional Glymphatic Abnormality in Behavioral Variant Frontotemporal Dementia[J]. Ann Neurol, 2023, 94(3): 442-456. DOI: 10.1002/ana.26710.
[36]
National Health Commission of the People's Republic of China. Guideline for prevention and treatment of cerebrovascular disease (2024 edition)[J]. Chin J Magn Reson Imaging, 2025, 16(1): 1-8. DOI: 10.12015/issn.1674-8034.2025.01.001.
[37]
Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019[J]. Lancet Neurol, 2021, 20(10): 795-820. DOI: 10.1016/S1474-4422(21)00252-0.
[38]
ZHANG S, YU W, ZHANG X, et al. Glymphatic dysfunction as a biomarker for post-stroke cognitive impairment[J/OL]. Sci Rep, 2025, 15(1): 19382 [2026-01-17]. https://pubmed.ncbi.nlm.nih.gov/40461672/. DOI: 10.1038/s41598-025-04054-9.
[39]
XIA X, REN Q, ZHANG J, et al. Altered brain glymphatic function on diffusion-tensorMRIin patients with spontaneous intracerebral hemorrhage: an exploratory study[J/OL]. Front Aging Neurosci, 2024, 16: 1506980 [2026-01-17]. https://pubmed.ncbi.nlm.nih.gov/39737332/. DOI: 10.3389/fnagi.2024.1506980.
[40]
WANG H, YU Q, ZHANG W, et al. Enlarged Perivascular Spaces (EPVS) Associated with Functional and Cognitive Outcome After Aneurysm Subarachnoid Hemorrhage (aSAH)[J]. Transl Stroke Res, 2025, 16(4): 1358-1368. DOI: 10.1007/s12975-024-01315-z.
[41]
WANG Y L. Diagnosis and Treatment of Cerebral Small Vessel Disease and the Way Of Future Exploration[J]. Chin J Stroke, 2024, 19(4): 363-374. DOI: 10.3969/j.issn.1673-5765.2024.04.001.
[42]
TIAN Y, CAI X, ZHOU Y, et al. Impaired glymphatic system as evidenced by low diffusivity along perivascular spaces is associated with cerebral small vessel disease: a population-based study[J]. Stroke Vasc Neurol, 2023, 8(5): 413-423. DOI: 10.1136/svn-2022-002191.
[43]
WANG J D J, LEOW Y J, VIPIN A, et al. Associations Between GFAP, Aβ42/40 Ratio, and Perivascular Spaces and Cognitive Domains in Vascular Cognitive Impairment[J/OL]. Int J Mol Sci, 2025, 26(8): 3541 [2026-01-17]. https://pubmed.ncbi.nlm.nih.gov/40332019/. DOI: 10.3390/ijms26083541.
[44]
ZHU H, ZHU C, LIU T, et al. Alterations in the Glymphatic System and Association with Brain Structure and Cognitive Function in Moyamoya Disease[J]. Transl Stroke Res, 2025, 16(4): 1173-1184. DOI: 10.1007/s12975-024-01296-z.
[45]
ZHOU Y, XUE R, LI Y, et al. Impaired Meningeal Lymphatics and Glymphatic Pathway in Patients with White Matter Hyperintensity[J/OL]. Adv Sci (Weinh), 2024, 11(26): e2402059 [2026-01-17]. https://pubmed.ncbi.nlm.nih.gov/38704728/. DOI: 10.1002/advs.202402059.
[46]
MAAS A I R, MENON D K, MANLEY G T, et al. Traumatic brain injury: progress and challenges in prevention, clinical care, and research[J]. Lancet Neurol, 2022, 21(11): 1004-1060. DOI: 10.1016/S1474-4422(22)00309-X.
[47]
BOLTE A C, DUTTA A B, HURT M E, et al. Meningeal lymphatic dysfunction exacerbates traumatic brain injury pathogenesis[J/OL]. Nat Commun, 2020, 11(1): 4524 [2026-01-17]. https://pubmed.ncbi.nlm.nih.gov/32913280/. DOI: 10.1038/s41467-020-18113-4.
[48]
YANG D X, SUN Z, YU M M, et al. Associations of MRI-Derived Glymphatic System Impairment With Global White Matter Damage and Cognitive Impairment in Mild Traumatic Brain Injury: A DTI-ALPS Study[J]. J Magn Reson Imaging, 2024, 59(2): 639-647. DOI: 10.1002/jmri.28797.
[49]
WANG X, DENG L, LIU X, et al. Relationship between glymphatic system dysfunction and cognitive impairment in patients with mild-to-moderate chronic traumatic brain injury: an analysis of the analysis along the perivascular space (ALPS) index[J]. Quant Imaging Med Surg, 2024, 14(12): 9246-9257. DOI: 10.21037/qims-24-895.
[50]
HUSSAIN R, TITHOF J, WANG W, et al. Potentiating glymphatic drainage minimizes post-traumatic cerebral oedema[J]. Nature, 2023, 623(7989): 992-1000. DOI: 10.1038/s41586-023-06737-7.
[51]
SUN Z, ZHENG Y. Metabolic diseases in the East Asian populations[J]. Nat Rev Gastroenterol Hepatol, 2025, 22(7): 500-516. DOI: 10.1038/s41575-025-01058-8.
[52]
CHEN B, MESEGUER D, LENCK S, et al. Rewiring of the glymphatic landscape in metabolic disorders[J]. Trends Endocrinol Metab, 2025, 36(8): 710-720. DOI: 10.1016/j.tem.2024.11.005.
[53]
XIA W, YIN X, ZHANG Y, et al. Gray Matter Reserve Modulates the Association between Glymphatic System Function and Cognition in Patients with Type 2 Diabetes Mellitus[J]. Neuroendocrinology, 2025, 115(1): 48-59. DOI: 10.1159/000542902.
[54]
PAN P, ZHANG D, LI J, et al. The enlarged perivascular spaces in the hippocampus is associated with memory function in patients with type 2 diabetes mellitus[J/OL]. Sci Rep, 2025, 15(1): 3644 [2026-01-17]. https://pubmed.ncbi.nlm.nih.gov/39880912/. DOI: 10.1038/s41598-025-87841-8.
[55]
XU S, WANG J, SUN K, et al. Cognitive Impairment in Chronic Kidney Disease Is Associated with Glymphatic System Dysfunction[J]. Kidney Dis (Basel), 2023, 9(5): 384-397. DOI: 10.1159/000530635.
[56]
CHEN B, LENCK S, THOMAS J L, et al. The glymphatic system as a nexus between obesity and neurological diseases[J]. Nat Rev Endocrinol, 2025, 21(1): 1-2. DOI: 10.1038/s41574-024-01042-3.
[57]
TU Y, FANG Y, LI G, et al. Glymphatic System Dysfunction Underlying Schizophrenia Is Associated With Cognitive Impairment[J]. Schizophr Bull, 2024, 50(5): 1223-1231. DOI: 10.1093/schbul/sbae039.
[58]
QIAN R, WANG L, FAN S, et al. Reduced coupling between global signal and cerebrospinal fluid inflow in patients with generalized anxiety disorder: A resting state functionalMRIstudy[J/OL]. J Affect Disord, 2025, 390: 119851 [2026-01-17]. https://pubmed.ncbi.nlm.nih.gov/40633781/. DOI: 10.1016/j.jad.2025.119851.
[59]
WANG C, ZHANG T, LU H, et al. Glymphatic dysfunction impairs cognitive function via disrupted white matter network efficiency in primary insomnia: A DTI-ALPS mediation study[J/OL]. Brain Res Bull, 2025, 233: 111640 [2026-01-17]. https://pubmed.ncbi.nlm.nih.gov/41242345/. DOI: 10.1016/j.brainresbull.2025.111640.
[60]
GUO J, ZHANG Z, MENG X, et al. Atrial fibrillation catheter ablation, brain glymphatic function, and cognitive performance[J]. Eur Heart J, 2025, 46(18): 1733-1743. DOI: 10.1093/eurheartj/ehaf036.
[61]
ZHENG C, CUI Y, QIN R, et al. Association of Glymphatic System Dysfunction with Cardiac Injury and Cognitive Impairment in Heart Failure: A MultimodalMRIStudy[J]. Acad Radiol, 2025, 32(6): 3227-3236. DOI: 10.1016/j.acra.2025.03.043.
[62]
XUE K, SHI Y, SONG F, et al. Glymphatic dysfunction in HIV: a resting-state fMRIbiomarker linking cognitive impairment and immune suppression[J]. Aids, 2025. DOI: 10.1097/QAD.0000000000004300.

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