{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:59:02Z","timestamp":1791230342977,"version":"4.1.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Mild stroke may lead to cognitive impairment, and it remains unclear whether intravenous thrombolysis (IVT) can mitigate cognitive deficits. This study investigates whether IVT can help alleviate cognitive function impairment in patients and further explores changes in the topological properties of cerebral blood flow (CBF) networks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This observational study prospectively enrolled 94 patients with acute mild ischemic stroke (44 IVT vs. 50 non-IVT) from two hospitals. A battery of neuropsychological tests and arterial spin labeling were performed to evaluate their cognitive functioning and CBF in 116 brain regions. Voxel-wise CBF was compared between patients and health controls. The CBF covariance network of patients was constructed by calculating across-subject CBF covariance among 116 brain regions. Network properties were calculated and compared between IVT and no-IVT groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The mild stroke group demonstrated significantly lower Montreal Cognitive Assessment (MoCA) scores compared to healthy controls (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001). Patients receiving IVT showed superior performance on the Trail Making Test-B (<jats:italic>p<\/jats:italic>\u202f=\u202f0.043), Clock Drawing Test (<jats:italic>p<\/jats:italic>\u202f=\u202f0.001), and Verbal Fluency Test (<jats:italic>p<\/jats:italic>\u202f=\u202f0.033). Multivariate regression analysis adjusted for covariates demonstrated significant associations between IVT and cognitive outcomes: Montreal Cognitive Assessment (<jats:italic>\u03b2<\/jats:italic>\u202f=\u202f2.85; 95% CI, 0.64\u20135.13), Trail Making Test-A (<jats:italic>\u03b2<\/jats:italic>\u202f=\u202f\u221216.90; 95% CI, \u221232.89\u2013-0.90), Trail Making Test-B (<jats:italic>\u03b2<\/jats:italic>\u202f=\u202f\u221243.27; 95% CI, \u221278.78\u2013-7.76), Hopkins Verbal Learning Test-Revised total recall (<jats:italic>\u03b2<\/jats:italic>\u202f=\u202f3.57; 95% CI, 1.36\u20135.78), HVLT-R delayed recall (<jats:italic>\u03b2<\/jats:italic>\u202f=\u202f1.53; 95% CI, 0.43\u20132.63), Clock Drawing Test (\u03b2\u202f=\u202f7.09; 95% CI, 2.40\u201311.79), and Verbal Fluency Test (<jats:italic>\u03b2<\/jats:italic>\u202f=\u202f3.00; 95% CI, 1.33\u20134.68). IVT patients exhibited higher small-worldness, clustering coefficient, and global efficiency of the network compared to non-IVT patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Intravenous thrombolysis demonstrated early cognitive benefits across multiple domains in patients with mild stroke. Improvement in the brain CBF covariance network properties may be the underlying mechanism.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2025.1513182","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T05:28:28Z","timestamp":1741325308000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Cognitive impairment after intravenous thrombolysis in mild stroke: assessment of cerebral blood flow covariance 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impairments following transient ischemic attack and minor stroke: a systematic review protocol","volume":"14","author":"Hede Ebbesen","year":"2023","journal-title":"Front Neurol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1007\/s11239-019-02001-w","article-title":"\u201cminor\u201d stroke: not a minor, still open question","volume":"49","author":"Rota","year":"2020","journal-title":"J Thromb Thrombolysis"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"I","DOI":"10.1177\/23969873211042192","article-title":"European stroke organisation and European academy of neurology joint guidelines on post-stroke cognitive impairment","volume":"6","author":"Quinn","year":"2021","journal-title":"Eur Stroke J"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e272","DOI":"10.1161\/STR.0000000000000430","article-title":"Cognitive impairment after ischemic and hemorrhagic stroke: a scientific statement from the American Heart Association\/American Stroke Association","volume":"54","author":"El Husseini","year":"2023","journal-title":"Stroke"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1001\/jama.2018.8496","article-title":"Effect of Alteplase vs aspirin on functional outcome for patients with acute ischemic stroke and minor nondisabling neurologic deficits: the Prisms randomized clinical trial","volume":"320","author":"Khatri","year":"2018","journal-title":"JAMA"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"760813","DOI":"10.3389\/fneur.2021.760813","article-title":"Acute ischemic stroke with mild symptoms-to Thrombolyse or not to Thrombolyse?","volume":"12","author":"Ferrari","year":"2021","journal-title":"Front Neurol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1002\/acn3.719","article-title":"Cognitive deficits in acute mild ischemic stroke and Tia and Effects of Rt-pa","volume":"6","author":"Rosenbaum Halevi","year":"2019","journal-title":"Annals Clinical Transl Neurol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"2341","DOI":"10.2147\/NDT.S434296","article-title":"Multidimensional outcomes of iv thrombolysis in minor ischemic stroke: motor, Psychocognitive, and dependence","volume":"19","author":"Li","year":"2023","journal-title":"Neuropsychiatr Dis Treat"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"2162","DOI":"10.1177\/0271678x15614846","article-title":"The effects of hemodynamic lag on functional connectivity and behavior after stroke","volume":"36","author":"Siegel","year":"2016","journal-title":"J Cerebral Blood Flow Metabol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s12916-017-0779-7","article-title":"Post-stroke dementia - a comprehensive review","volume":"15","author":"Mijajlovi\u0107","year":"2017","journal-title":"BMC Med"},{"key":"ref11","first-page":"505","article-title":"Statistical image analysis of cerebral blood flow in vascular dementia with 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Healthy Longev"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1002\/alz.13408","article-title":"Lower cerebral blood flow predicts cognitive decline in patients with vascular cognitive impairment","volume":"20","author":"van Dinther","year":"2023","journal-title":"Alzheimers Dement"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"211","DOI":"10.3389\/fnagi.2016.00211","article-title":"Cerebral blood flow alterations as assessed by 3d Asl in cognitive impairment in patients with subcortical vascular cognitive impairment: a marker for disease severity","volume":"8","author":"Sun","year":"2016","journal-title":"Front Aging Neurosci"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1238411","DOI":"10.1126\/science.1238411","article-title":"Structural and functional brain networks: from connections to 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Neurochem"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"111203","DOI":"10.1016\/j.pscychresns.2020.111203","article-title":"Alterations of cerebral blood flow network in behavioral variant frontotemporal dementia patients with and without apathy","volume":"307","author":"Zhou","year":"2021","journal-title":"Psychiatry Res Neuroimaging"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1161\/CIRCRESAHA.122.319951","article-title":"Post-stroke cognitive impairment and dementia","volume":"130","author":"Rost","year":"2022","journal-title":"Circ Res"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e1879","DOI":"10.1212\/WNL.0000000000005553","article-title":"Identification of a specific functional network altered in Poststroke cognitive 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