{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:17:01Z","timestamp":1792793821912,"version":"4.5.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and purpose<\/jats:title>\n                    <jats:p>The glymphatic system, a waste clearance pathway, has been implicated in several neurological conditions associated with neuroinflammation. COVID-19 associated neurocognitive impairment, part of the post-acute sequelae of SARS-CoV-2 infection (PASC), is strongly associated with neuroinflammation and disrupted blood-brain barrier (BBB). Several studies have implicated a synergistic interaction between the glymphatic system dysfunction and BBB disruption. In this proof-of-concept study, we investigated the role of the MRI metric diffusion along the perivascular spaces DTI (DTI-ALPS) in patients with PASC and correlated this with the BBB capillary permeability metric- K trans derived from Dynamic contrast enhanced (DCE) perfusion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>14 subjects with PASC who had persisting symptoms of anosmia, ageusia, fatigue, and cognitive impairment (CI) and ten healthy age and sex matched controls were recruited. All PASC subjects underwent routine and advanced MR brain imaging at two time points, (3 months +\/- 2 weeks) after initial infection - referred as Time Point 1 (TP-1) - and 10 repeated the MRI scan 12 months (+\/- 2 weeks) later - referred as Time Point 2 (TP-2), while the controls had MR imaging done only at TP-1. All had mild neurocognitive impairment. In the final analysis we included those who had DTI study at both time points (n-10). MR imaging included DCE perfusion and DTI in addition to anatomical imaging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Statistical analysis<\/jats:title>\n                    <jats:p>Given the small size of the sample and nonnormality of data in the descriptive analyses, nonparametric analyses were used for group comparisons. A two-sample Wilcoxon rank sum test was used to show the differences in DTI-ALPS between the patients and controls in the predefined regions of interest. Spearman\u2019s correlation coefficient (rho) was used to assess the correlation between DTI-ALPS index with K trans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      There was significant reduction in the DTI-ALPS index between the patients and controls in the left hemisphere (z\u2009=\u20092.04,\n                      <jats:italic>p\u2009&lt;<\/jats:italic>\n                      \u20090.04). However, there was no significant change over time in the index. There was a strong inverse correlation between the central white matter K trans and DTI-ALPS index (rho\u2009=\u20090.66,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.03).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study indicates that disordered para vascular drainage, a marker for glymphatic system and BBB damage may contribute to neurocognitive impairment (NCI) among patients with PASC. The DTI-ALPS index, which does not require contrast injection, has the potential to serve as a non-invasive biomarker.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12883-025-04133-4","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T03:10:51Z","timestamp":1742353851000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Asymmetrical glymphatic dysfunction in patients with long Covid associated neurocognitive impairment- correlation with BBB disruption"],"prefix":"10.1186","volume":"25","author":[{"given":"Joga R.","family":"Chaganti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanush K.","family":"Talekar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce James","family":"Brew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,19]]},"reference":[{"issue":"8","key":"4133_CR1","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1002\/acn3.51825","volume":"10","author":"LA Cysique","year":"2023","unstructured":"Cysique LA, Jakabek D, Bracken SG, Allen-Davidian Y, Heng B, Chow S, et al. The kynurenine pathway relates to post\u2010acute COVID\u201019 objective cognitive impairment and PASC. Ann Clin Transl Neurol. 2023;10(8):1338\u201352.","journal-title":"Ann Clin Transl Neurol"},{"key":"4133_CR2","doi-asserted-by":"crossref","unstructured":"Chaganti J, Poudel G, Cysique LA, Dore GJ, Kelleher A, Matthews G et al. Blood brain barrier disruption and glutamatergic excitotoxicity in post-acute sequelae of SARS COV-2 infection cognitive impairment: potential biomarkers and a window into pathogenesis. Front Neurol. 2024;15.","DOI":"10.3389\/fneur.2024.1350848"},{"issue":"2","key":"4133_CR3","doi-asserted-by":"publisher","first-page":"377","DOI":"10.3390\/biomedicines11020377","volume":"11","author":"IZ Ong","year":"2023","unstructured":"Ong IZ, Kolson DL, Schindler MK. Mechanisms, effects, and management of neurological complications of post-acute sequelae of COVID-19 (NC-PASC). 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Korean J Radiol. 2020;21(11):1199.","journal-title":"Korean J Radiol"}],"container-title":["BMC Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12883-025-04133-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12883-025-04133-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12883-025-04133-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T03:10:54Z","timestamp":1742353854000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcneurol.biomedcentral.com\/articles\/10.1186\/s12883-025-04133-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,19]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4133"],"URL":"https:\/\/doi.org\/10.1186\/s12883-025-04133-4","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-4551571\/v1","asserted-by":"object"}]},"ISSN":["1471-2377"],"issn-type":[{"value":"1471-2377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,19]]},"assertion":[{"value":"8 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"(Local ethics approval was obtained from St Vincents Hospital, Sydney, Australia, Hospital Human Research Ethics Committee- (Approval:2022\/ETH0022). All the participants provided written informed consent prior to Enrolment. The study was conducted in adherence to the principles outlined in the Declaration of Helsinki and relevant regulatory guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not Applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"all human participants involved in the study provided informed consent to take part in the research, meaning they understood the study\u2019s details and willingly agreed to participate, as required by ethical guidelines for research involving humans.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"112"}}