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2000
Volume 21, Issue 1
  • ISSN: 1573-4056
  • E-ISSN: 1875-6603

Abstract

Background

Glymphatic dysfunction is proposed as a final common pathway to dementia. Cognitive impairment following ischemic stroke can gradually worsen, potentially leading to post-stroke dementia. This study aimed to examine the changes in glymphatic function in post-stroke patients and explore its relationship with cognition.

Methods

A total of thirty-two post-stroke patients and twenty-seven healthy controls (HCs) matched for age, sex, and educational level were enrolled in this study. All participants underwent neurological MRI scans and comprehensive cognitive assessments six months following the onset of the stroke. Three glymphatic markers derived from MRI were quantified, including diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, choroid plexus volume (CPV), and enlarged perivascular spaces (PVS) volume. The changes in glymphatic markers and their correlations with cognitive scores were analyzed.

Results

Post-stroke patients exhibited a significantly decreased DTI-ALPS index ( < 0.001) and an increased CPV ( < 0.001) compared to HCs, while no significant difference was observed in PVS volume. Correlation analysis revealed that the DTI-ALPS index was positively correlated with Digit Span Test ( = 0.426, = 0.015) and Digit Symbol Substitution Test ( = 0.363, = 0.041) scores, and PVS volume showed a positive correlation with Trail Making Test-B scores ( = 0.391, = 0.027). After adjusting for confounding factors, multiple linear regression analyses indicated that enlarged PVS volume was independently associated with worse performance in Trail Making Test-B ( = 0.428, = 0.010).

Discussion

The findings demonstrated that glymphatic dysfunction, as indicated by a reduced DTI-ALPS index and increased CPV volume, was evident in post-stroke patients and significantly linked to impairments in specific cognitive domains, including working memory, processing speed, and executive function. These observations supported the hypothesis that glymphatic impairment may represent a key mechanistic pathway underlying post-stroke cognitive impairment (PSCI). To further elucidate the causal relationships and identify potential therapeutic targets, future studies incorporating larger cohorts, longitudinal designs, and region-specific PVS analyses are warranted.

Conclusion

Post-stroke patients exhibited a reduced DTI-ALPS index and an increased CPV, potentially reflecting impaired glymphatic function. Furthermore, these metrics were associated with specific cognitive domains.

This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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References

  1. El HusseiniN. KatzanI.L. RostN.S. BlakeM.L. ByunE. PendleburyS.T. AparicioH.J. MarquineM.J. GottesmanR.F. SmithE.E. Cognitive impairment after ischemic and hemorrhagic stroke: A scientific statement from the American Heart Association/American stroke association.Stroke2023546e272e29110.1161/STR.000000000000043037125534
    [Google Scholar]
  2. DichgansM. LeysD. Vascular cognitive impairment.Circ. Res.2017120357359110.1161/CIRCRESAHA.116.30842628154105
    [Google Scholar]
  3. IliffJ.J. WangM. LiaoY. PloggB.A. PengW. GundersenG.A. BenvenisteH. VatesG.E. DeaneR. GoldmanS.A. NagelhusE.A. NedergaardM. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β.Sci. Transl. Med.20124147147ra11110.1126/scitranslmed.300374822896675
    [Google Scholar]
  4. RasmussenM.K. MestreH. NedergaardM. The glymphatic pathway in neurological disorders.Lancet Neurol.201817111016102410.1016/S1474‑4422(18)30318‑130353860
    [Google Scholar]
  5. NedergaardM. GoldmanS.A. Glymphatic failure as a final common pathway to dementia.Science20203706512505610.1126/science.abb873933004510
    [Google Scholar]
  6. TaokaT. MasutaniY. KawaiH. NakaneT. MatsuokaK. YasunoF. KishimotoT. NaganawaS. 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.Jpn. J. Radiol.201735417217810.1007/s11604‑017‑0617‑z28197821
    [Google Scholar]
  7. ZhangW. ZhouY. WangJ. GongX. ChenZ. ZhangX. CaiJ. ChenS. FangL. SunJ. LouM. Glymphatic clearance function in patients with cerebral small vessel disease.Neuroimage202123811825710.1016/j.neuroimage.2021.11825734118396
    [Google Scholar]
  8. ChoiJ.D. MoonY. KimH.J. YimY. LeeS. MoonW.J. Choroid plexus volume and permeability at brain MRI within the Alzheimer disease clinical spectrum.Radiology2022304363564510.1148/radiol.21240035579521
    [Google Scholar]
  9. JiangJ. ZhuoZ. WangA. LiW. JiangS. DuanY. RenQ. ZhaoM. WangL. YangS. AwanM.U.N. LiuY. XuJ. Choroid plexus volume as a novel candidate neuroimaging marker of the Alzheimer’s continuum.Alzheimers Res. Ther.202416114910.1186/s13195‑024‑01520‑w38961406
    [Google Scholar]
  10. JeongS.H. JeongH.J. SunwooM.K. AhnS.S. LeeS.K. LeeP.H. KimY.J. SohnY.H. ParkC.J. ChungS.J. Association between choroid plexus volume and cognition in Parkinson disease.Eur. J. Neurol.202330103114312310.1111/ene.1599937498202
    [Google Scholar]
  11. HongH. HongL. LuoX. ZengQ. LiK. WangS. JiaerkenY. ZhangR. YuX. ZhangY. LeiC. LiuZ. ChenY. HuangP. ZhangM. The relationship between amyloid pathology, cerebral small vessel disease, glymphatic dysfunction, and cognition: A study based on Alzheimer’s disease continuum participants.Alzheimers Res. Ther.20241614310.1186/s13195‑024‑01407‑w38378607
    [Google Scholar]
  12. LiH. JacobM.A. CaiM. KesselsR.P.C. NorrisD.G. DueringM. De LeeuwF.E. TuladharA.M. Perivascular spaces, diffusivity along perivascular spaces, and free water in cerebral small vessel disease.Neurology20241029e20930610.1212/WNL.000000000020930638626373
    [Google Scholar]
  13. AndriutaD. OttoyJ. RuthirakuhanM. FelicianoG. DilliottA.A. HegeleR.A. GaoF. McLaughlinP.M. RabinJ.S. Wood AlexanderM. ScottC.J.M. YhapV. BerezukC. OzzoudeM. SwardfagerW. ZebarthJ. TartagliaM.C. RogaevaE. Tang-WaiD.F. CasaubonL. KumarS. DowlatshahiD. MandziaJ. SahlasD. SaposnikG. FischerC.E. BorrieM. HassanA. BinnsM.A. FreedmanM. ChertkowH. FingerE. FrankA. BarthaR. SymonsS. ZetterbergH. SwartzR.H. MasellisM. BlackS.E. RamirezJ. Perivascular spaces, plasma GFAP, and speeded executive function in neurodegenerative diseases.Alzheimers Dement.20242085800580810.1002/alz.1408138961774
    [Google Scholar]
  14. ZhuJ. MoJ. LiuK. ChenQ. LiZ. HeY. ChangY. LinC. YuM. XuY. TanX. HuangK. PanS. Glymphatic system impairment contributes to the formation of brain edema after ischemic stroke.Stroke20245551393140410.1161/STROKEAHA.123.04594138533660
    [Google Scholar]
  15. JiC. YuX. XuW. LenahanC. TuS. ShaoA. The role of glymphatic system in the cerebral edema formation after ischemic stroke.Exp. Neurol.202134011368510.1016/j.expneurol.2021.11368533676917
    [Google Scholar]
  16. TohC.H. SiowT.Y. Glymphatic dysfunction in patients with ischemic stroke.Front. Aging Neurosci.20211375624910.3389/fnagi.2021.75624934819849
    [Google Scholar]
  17. NasreddineZ.S. PhillipsN.A. BédirianV. CharbonneauS. WhiteheadV. CollinI. CummingsJ.L. ChertkowH. The montreal cognitive assessment, MoCA: A brief screening tool for mild cognitive impairment.J. Am. Geriatr. Soc.200553469569910.1111/j.1532‑5415.2005.53221.x15817019
    [Google Scholar]
  18. FolsteinM.F. FolsteinS.E. McHughP.R. “Mini-mental state”.J. Psychiatr. Res.197512318919810.1016/0022‑3956(75)90026‑61202204
    [Google Scholar]
  19. GuoQ. ZhaoQ. ChenM. DingD. HongZ. A comparison study of mild cognitive impairment with 3 memory tests among Chinese individuals.Alzheimer Dis. Assoc. Disord.200923325325910.1097/WAD.0b013e3181999e9219812468
    [Google Scholar]
  20. StraussE. ShermanE.M.S. SpreenO. A compendium of neuropsychological tests: Administration, norms, and commentary.Appl. Neuropsychol.2007141626310.1080/09084280701280502
    [Google Scholar]
  21. TombaughT. Trail making test A and B: Normative data stratified by age and education.Arch. Clin. Neuropsychol.200419220321410.1016/S0887‑6177(03)00039‑815010086
    [Google Scholar]
  22. EismaJ.J. McKnightC.D. HettK. ElenbergerJ. HanC.J. SongA.K. ConsidineC. ClaassenD.O. DonahueM.J. Deep learning segmentation of the choroid plexus from structural magnetic resonance imaging (MRI): Validation and normative ranges across the adult lifespan.Fluids Barriers CNS20242112110.1186/s12987‑024‑00525‑938424598
    [Google Scholar]
  23. BoutinaudP. TsuchidaA. LaurentA. AdoniasF. HanifehlouZ. NozaisV. VerrecchiaV. LampeL. ZhangJ. ZhuY.C. TzourioC. MazoyerB. JoliotM. 3D segmentation of perivascular spaces on T1-weighted 3 tesla MR images with a convolutional autoencoder and a U-shaped neural network.Front. Neuroinform.20211564160010.3389/fninf.2021.64160034262443
    [Google Scholar]
  24. PuT. ZouW. FengW. ZhangY. WangL. WangH. XiaoM. Persistent malfunction of glymphatic and meningeal lymphatic drainage in a mouse model of subarachnoid hemorrhage.Exp. Neurobiol.201928110411810.5607/en.2019.28.1.10430853828
    [Google Scholar]
  25. WangM. IliffJ.J. LiaoY. ChenM.J. ShinsekiM.S. VenkataramanA. CheungJ. WangW. NedergaardM. Cognitive deficits and delayed neuronal loss in a mouse model of multiple microinfarcts.J. Neurosci.20123250179481796010.1523/JNEUROSCI.1860‑12.201223238711
    [Google Scholar]
  26. StanzioneR. ForteM. CotugnoM. BianchiF. MarchittiS. RubattuS. Role of DAMPs and of leukocytes infiltration in ischemic stroke: Insights from animal models and translation to the human disease.Cell. Mol. Neurobiol.202242354555610.1007/s10571‑020‑00966‑432996044
    [Google Scholar]
  27. PavanC. L R XavierA. RamosM. FisherJ. KritsilisM. LinderA. BentzerP. NedergaardM. LundgaardI. DNase treatment prevents cerebrospinal fluid block in early experimental pneumococcal meningitis.Ann. Neurol.202190465366910.1002/ana.2618634397111
    [Google Scholar]
  28. ZouK. DengQ. ZhangH. HuangC. Glymphatic system: A gateway for neuroinflammation.Neural Regen. Res.202419122661267210.4103/1673‑5374.39131238595285
    [Google Scholar]
  29. GaberelT. GakubaC. GoulayR. De LizarrondoS.M. HanouzJ.L. EmeryE. TouzeE. VivienD. GaubertiM. Impaired glymphatic perfusion after strokes revealed by contrast-enhanced MRI: A new target for fibrinolysis?Stroke201445103092309610.1161/STROKEAHA.114.00661725190438
    [Google Scholar]
  30. MunicioC. CarreroL. AntequeraD. CarroE. Choroid plexus aquaporins in CSF homeostasis and the glymphatic system: Their relevance for Alzheimer’s disease.Int. J. Mol. Sci.202324187810.3390/ijms2401087836614315
    [Google Scholar]
  31. PreziosaP. PaganiE. MeaniA. StorelliL. MargoniM. YudinY. TedoneN. BiondiD. RubinM. RoccaM.A. FilippiM. Chronic active lesions and larger choroid plexus explain cognition and fatigue in multiple sclerosis.Neurol. Neuroimmunol. Neuroinflamm.2024112e20020510.1212/NXI.000000000020020538350048
    [Google Scholar]
  32. WangX. DengL. LiuX. ChengS. ZhanY. ChenJ. 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.Quant. Imaging Med. Surg.202414129246925710.21037/qims‑24‑89539698597
    [Google Scholar]
  33. ZhuH. ZhuC. LiuT. Alterations in the glymphatic system and association with brain structure and cognitive function in Moyamoya disease.Transl. Stroke Res.20241641173118410.1007/s12975‑024‑01296‑z39245689
    [Google Scholar]
  34. ZhangX. WangY. JiaoB. WangZ. ShiJ. ZhangY. BaiX. LiZ. LiS. BaiR. SuiB. Glymphatic system impairment in Alzheimer’s disease: Associations with perivascular space volume and cognitive function.Eur. Radiol.20233421314132310.1007/s00330‑023‑10122‑337610441
    [Google Scholar]
  35. TangJ. ZhangM. LiuN. XueY. RenX. HuangQ. ShiL. FuJ. The association between glymphatic system dysfunction and cognitive impairment in cerebral small vessel disease.Front. Aging Neurosci.20221491663310.3389/fnagi.2022.91663335813943
    [Google Scholar]
  36. XieL. KangH. XuQ. ChenM.J. LiaoY. ThiyagarajanM. O’DonnellJ. ChristensenD.J. NicholsonC. IliffJ.J. TakanoT. DeaneR. NedergaardM. Sleep drives metabolite clearance from the adult brain.Science2013342615637337710.1126/science.124122424136970
    [Google Scholar]
  37. ShankarG.M. LiS. MehtaT.H. Garcia-MunozA. ShepardsonN.E. SmithI. BrettF.M. FarrellM.A. RowanM.J. LemereC.A. ReganC.M. WalshD.M. SabatiniB.L. SelkoeD.J. Amyloid-β protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory.Nat. Med.200814883784210.1038/nm178218568035
    [Google Scholar]
  38. LiddelowS.A. GuttenplanK.A. ClarkeL.E. BennettF.C. BohlenC.J. SchirmerL. BennettM.L. MünchA.E. ChungW.S. PetersonT.C. WiltonD.K. FrouinA. NapierB.A. PanickerN. KumarM. BuckwalterM.S. RowitchD.H. DawsonV.L. DawsonT.M. StevensB. BarresB.A. Neurotoxic reactive astrocytes are induced by activated microglia.Nature2017541763848148710.1038/nature2102928099414
    [Google Scholar]
  39. DingJ. SigurðssonS. JónssonP.V. EiriksdottirG. CharidimouA. LopezO.L. van BuchemM.A. GuðnasonV. LaunerL.J. Large perivascular spaces visible on magnetic resonance imaging, cerebral small vessel disease progression, and risk of dementia.JAMA Neurol.20177491105111210.1001/jamaneurol.2017.139728715552
    [Google Scholar]
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