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A combination of biofluid and neuroimaging markers may better profile early stage VCID than individual measures. Here, we tested this possibility focusing on plasma levels of S100 calcium-binding protein B (S100B), which has been linked with blood\u2013brain-barrier (BBB) integrity, and neuroimaging measures assessing BBB function (water exchange rate across the BBB (k<jats:sub>w<\/jats:sub>)) and cerebral small vessel disease (white matter hyperintensities (WMHs)). A total of 74 older adults without dementia had plasma samples collected and underwent cognitive assessment. A subsample had neuroimaging data including diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL) for assessment of BBB k<jats:sub>w<\/jats:sub> and T2-weighted fluid-attenuated inversion recovery (FLAIR) for quantification of WMHs. Results indicated that higher plasma S100B levels were associated with poorer episodic memory performance (<jats:italic>\u03b2<\/jats:italic>\u2009= \u2212\u2009.031, SE\u2009=\u2009.008, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001). Moreover, significant interactions were observed between plasma S100B levels and parietal lobe BBB k<jats:sub>w<\/jats:sub> (interaction <jats:italic>\u03b2<\/jats:italic>\u2009=\u2009.095, SE\u2009=\u2009.042, <jats:italic>p<\/jats:italic>\u2009=\u2009.028) and between plasma S100B levels and deep WMH volume (interaction <jats:italic>\u03b2<\/jats:italic>\u2009= \u2212\u2009.025, SE\u2009=\u2009.009, <jats:italic>p<\/jats:italic>\u2009=\u2009.007) for episodic memory. Individuals with the poorest memory performance showed both high plasma S100B and either low BBB k<jats:sub>w<\/jats:sub> in the parietal lobe or increased deep WMH burden. Taken together, our results provide support for the combined use of biofluid and neuroimaging markers in the study of VCID.<\/jats:p>","DOI":"10.1007\/s11357-024-01498-1","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T11:09:53Z","timestamp":1738753793000},"page":"3131-3146","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Synergistic effects of plasma S100B and MRI measures of cerebrovascular disease on cognition in older adults"],"prefix":"10.1007","volume":"47","author":[{"given":"Colleen","family":"Pappas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher E.","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentinos","family":"Zachariou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. 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