{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T06:26:15Z","timestamp":1787984775734,"version":"build-2784847793"},"update-to":[{"DOI":"10.12688\/f1000research.157890.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000}}],"reference-count":86,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>Background Cerebral small vessel disease (cSVD) is a progressive neurovascular-degenerative condition without specific treatment that causes lacunar stroke, most intracerebral haemorrhage, vascular cognitive impairment (VCI) and several neuropsychiatric conditions. Objectives To conduct a rapid multi-stage scoping review to identify licensed interventions that could be repurposed for testing in cSVD at phase-3. Methods First, we screened preclinical studies of potential relevance to cSVD and used a drug dictionary to identify studies of potential interventions. Separately, we screened clinical studies of relevance to cSVD and VCI. Following merging, we removed drugs that were unsuitable or impractical to assess long-term in the UK. We then performed mini-meta-analyses for shortlisted interventions assessing effects on cognition and scored these for their relevance to cSVD. Results The preclinical review created a long-list of 1,757 deduplicated interventions. Those that were available in the UK, not expensive or impractical to administer long-term were merged with 62 interventions identified from 75 relevant clinical studies to create a medium-list of 52 interventions. Focussed literature review short-listed ten interventions for review by an Independent Scientific Advisory Group; they ranked three as most suitable for immediate testing: metformin, tadalafil and isosorbide mononitrate. Conclusion This rapid review identified three interventions that are suitable for testing in a late phase-3 (platform) trial involving patients with cSVD. The approach could be improved with partial automation, text mining and generative pre-trained transformer approaches which would help manage the large data volumes. Further, our data-driven approach could be combined with genetic or other mechanistic methods to further de-risk future trials.<\/ns3:p>","DOI":"10.12688\/f1000research.157890.2","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T15:50:08Z","timestamp":1757519408000},"page":"1546","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Developing treatments for cerebral small vessel disease: a scoping review of licensed interventions for potential repurposing"],"prefix":"10.12688","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2734-5132","authenticated-orcid":false,"given":"Philip M","family":"Bath","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth P","family":"Phan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwynneth","family":"Clay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse","family":"Dawson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paresh","family":"Malhotra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob","family":"Howard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suvankar","family":"Pal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9812-6642","authenticated-orcid":false,"given":"Joanna M","family":"Wardlaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry","family":"Quinn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9187-9839","authenticated-orcid":false,"given":"Malcolm","family":"Macleod","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2673-2734","DOI":"10.1016\/S0140-6736(17)31363-6","article-title":"Dementia prevention, intervention, and care.","volume":"390","author":"G Livingston","year":"2017","journal-title":"Lancet."},{"key":"ref2","first-page":"e105-e125","article-title":"Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019.","volume":"7","year":"2022","journal-title":"Lancet Public Health."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"e859-e867","DOI":"10.1016\/S2468-2667(23)00214-1","article-title":"Dementia incidence trend in England and Wales, 2002-19, and projection for dementia burden to 2040: analysis of data from the English Longitudinal Study of Ageing.","volume":"8","author":"Y Chen","year":"2023","journal-title":"Lancet Public Health."},{"key":"ref4","first-page":"1-13","article-title":"Cognitive impairment in patients with cerebrovascular disease: A white paper from the ESO Dementia Committee.","author":"A Verdelho","year":"2021","journal-title":"Eur. 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.173409.r392611, Jade L. Taylor, University of California Davis, Davis, California, 22 Jul 2025, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/13-1546\/v1#referee-response-392611","order":0,"name":"referee-response-392611","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Philip Bath<\/b>; \n<i>Posted: 11 Aug 2025<\/i>; We thank Dr Taylor for their helpful comments.  Page 2, Paragraph 2 (Results section of the abstract):&nbsp;The phrase \u201cthose that were&nbsp;\n<i>not<\/i>&nbsp;available in the UK\u201d should be corrected to \u201cthose that were available in the UK.\u201d  \n<b>Thank you \u2013 we have corrected this in Abstract\/Results..<\/b> \n<b>CHANGE<\/b>  ISAG Criteria:&nbsp;The criteria employed by the ISAG should be introduced earlier in the manuscript\u2014preferably in the methods section\u2014and clearly linked to Table 5 for clarity.  \n<b>Thank you \u2013 we have expanded on the criteria assessed by ISAG in the Methods\/Independent review section with a link to Table 5.<\/b> \n<b>We have also corrected the use of Independent Scientific Advisory Committee (ISAC) by changing to \u2026 Group (ISAG) in the Header of Table 5 and text (sections Overview, Table 3 and Independent review\u2026) for consistency with the original NIHR research call.<\/b> \n<b>CHANGE<\/b>  The inclusion of only English-language studies should be explicitly acknowledged as a limitation, as it may have resulted in the exclusion of relevant non-English literature.  \n<b>Thank you \u2013 we have added this point to the Discussion\/limitations section (added to limitation 2.<\/b> \n<b>CHANGE<\/b>  The limitations of converting standardized mean differences from before-after studies to odds ratios for comparison purposes should be discussed, as this transformation may introduce bias or imprecision in effect estimates.  \n<b>Thank you \u2013 we have added this point to the Discussion\/limitations section (new limitation 7).<\/b> \n<b>CHANGE<\/b>","URL":"https:\/\/f1000research.com\/articles\/13-1546\/v2#referee-comment-14344","order":1,"name":"referee-comment-14344","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.173409.r392606, Maria Clara Zanon Zotin, Universidade de Sao Paulo, S\u00e3o Paulo, State of S\u00e3o Paulo, 09 Aug 2025, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/13-1546\/v1#referee-response-392606","order":2,"name":"referee-response-392606","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}