Journal Article
Synergistic effects of plasma S100B and MRI measures of cerebrovascular disease on cognition in older adults
Colleen Pappas; Christopher E. Bauer; Valentinos Zachariou; T. J. Libecap; Beatriz Rodolpho; Tiffany L. Sudduth; Peter T. Nelson; Gregory A. Jicha; Anika MS Hartz; Xingfeng Shao; Danny J. J. Wang; Brian T. Gold
GeroScience · Vol. 47, Issue 3 · pp. 3131-3146 · 2025
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 (k w )) 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 w 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 k w (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 k w 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.