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We examined relationships between a panel of 13 blood biomarkers and magnetic resonance imaging\u00a0(MRI) markers of SVD (structural lesions, diffusion\u2010weighted imaging [DWI]\u2010positive lesions, blood\u2010brain barrier (BBB) permeability, and cerebrovascular reactivity (CVR), and cognition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>In linear mixed models, vascular endothelial growth factor was significantly associated with incident DWI\u2010positive lesions over 1 year. Intercellular adhesion molecule\u20101 was linked with lower CVR while platelet\u2010derived growth factor\u2010subunit B and Endothelin\u20101 were associated with higher CVR. Platelet\u2010Selectin levels were associated with mild cognitive impairment at 1 year.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Our results support the role of endothelial and pericyte dysfunction in SVD burden and progression and suggest that specific biomarkers relate to distinct SVD manifestations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Small vessel disease (SVD) lacks specific or predictive biomarker signatures.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Vascular endothelial growth factor levels were linked to incident lesions detected over 1 year.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Circulating intercellular adhesion molecule\u20101 related to lower cerebrovascular reactivity.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Platelet\u2010selectin levels were associated with mild cognitive impairment longitudinally.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>These findings could help stratify patients at high\u2010risk of rapid\u2010progression SVD.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70152","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T04:15:18Z","timestamp":1745554518000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Blood biomarkers of vascular dysfunction in small vessel disease progression: Insights from a longitudinal neuroimaging study"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9457-9855","authenticated-orcid":false,"given":"Daniela","family":"Jaime Garcia","sequence":"first","affiliation":[{"name":"Centre for Clinical Brain Sciences School of Clinical Sciences College of Medicine and Veterinary Medicine The University of Edinburgh  Edinburgh UK"},{"name":"UK Dementia Research Institute at the University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Una","family":"Clancy","sequence":"additional","affiliation":[{"name":"Centre for Clinical Brain Sciences School of Clinical Sciences College of Medicine and Veterinary Medicine The University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Arteaga","sequence":"additional","affiliation":[{"name":"Centre for Clinical Brain Sciences School of Clinical Sciences College of Medicine and Veterinary Medicine The University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C.","family":"Vald\u00e9s\u2010Hernandez","sequence":"additional","affiliation":[{"name":"Centre for Clinical Brain Sciences School of Clinical Sciences College of Medicine and Veterinary Medicine The University of Edinburgh  Edinburgh UK"},{"name":"UK Dementia Research Institute at the University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca M.","family":"Chappell","sequence":"additional","affiliation":[{"name":"Centre for Clinical Brain Sciences School of Clinical Sciences College of Medicine and Veterinary Medicine The University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela C. 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