Abstract

There is growing interest in studying vascular contributions to cognitive impairment and dementia (VCID) and developing biomarkers to identify at-risk individuals. 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– brain-barrier (BBB) integrity, and neuroimaging measures assessing BBB function (water exchange rate across the BBB (kw)) 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 kw 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 (β = − .031, SE = .008, p < .001). Moreover, significant interactions were observed between plasma S100B levels and parietal lobe BBB kw (interaction β = .095, SE = .042, p = .028) and between plasma S100B levels and deep WMH volume (interaction β = − .025, SE = .009, p = .007) for episodic memory. Individuals with the poorest memory performance showed both high plasma S100B and either low BBB kw 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.

Document Type

Article

Publication Date

2-2025

Digital Object Identifier (DOI)

https://doi.org/10.1007/s11357-024-01498-1

Funding Information

The current study was supported by the National Institutes of Health (NIH), grants: NINDS RF1 NS122028, NIA R01 AG068055, NIA R01 AG055449, NIA P30 AG072946, NINDS R01 NS134712, and NIA P30 AG028383 ‐ 15S. This publication was also supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH, through Grant UL1TR001998. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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