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Inflammation has been hypothesized to play a role in disease pathogenesis and also in progression to vascular cognitive impairment and dementia (VCID), suggesting that targeting inflammation may offer a novel treatment option.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>In this review, we aimed to summarize the evidence that both systemic and central nervous system (CNS) inflammation occur in SVD and VCID, critically examine whether associations are causal, and review the evidence that anti-inflammatory interventions might represent possible treatments. We include coverage of sporadic SVD, cerebral amyloid angiopathy, and genetic small vessel diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary of review:<\/jats:title>\n                    <jats:p>\n                      CNS inflammation has been demonstrated in SVD both in post-mortem brains and\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      using positron emission tomography with radioligands targeted against the translocator surface proteins in microglia, but robust evidence showing such changes are causally related to disease progression is lacking. Peripheral inflammation can be measured in the blood using targeted assays and, more recently, large-scale proteomic panels. Proteins involved in coagulation, endothelial cell activation, and immune cell adhesion have been associated with SVD, as well as specific cytokines, although not all findings have been replicated, and there are limited data examining whether individual proteins predict future disease progression. Genetic data can be used to inform whether such associations are likely to be causal and prioritize treatment targets. However, to date, few treatment trials have investigated whether drugs that target specific inflammatory pathways can reduce SVD progression and onset of VCID, and those that have been performed have used non-specific inhibitors such as minocycline and colchicine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Considerable data support the presence of both systemic and CNS inflammation in SVD and VCID. However, whether these associations are causal remains unclear, and more longitudinal and interventional studies are required. A better understanding of the molecular basis of inflammation and immune dysfunction in SVD also allows more precise therapeutic targeting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17474930261461366","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T12:22:31Z","timestamp":1780921351000},"page":"1246-1259","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["The role of inflammation in cerebral small vessel disease and vascular cognitive impairment, and therapeutic implications"],"prefix":"10.1177","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0431-7841","authenticated-orcid":false,"given":"Robin B","family":"Brown","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart M","family":"Allan","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK"},{"name":"Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, The University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh S","family":"Markus","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,7,12]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/17474930251404243"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0b013e3182299496"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.181"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2025.3242"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.04.034"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.12.015"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30079-1"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00131-X"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094958"},{"key":"e_1_3_2_11_2","article-title":"An introduction to therapeutic approaches to vascular cognitive impairment","volume":"2","author":"Hainsworth AH","year":"2021","unstructured":"Hainsworth AH, Elahi FM, Corriveau RA. 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