Synergistic effects of plasma S100B and MRI measures of cerebrovascular disease on cognition in older adults

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.