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

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.

Keywords: Blood–brain barrier; Diffusion; Memory; S100B; Vascular contributions to cognitive impairment and dementia; White matter hyperintensities.

Fig. 1

Regions of interest for k_w maps. Regions of interest (ROIs) for k_w analyses displayed on a representative participant. A The diffusion prepared arterial spin labeling (DP-pcASL) M0 image with the T1-weighted image (red outline) aligned. B The frontal lobar (green), parietal lobar (yellow), and portions of precuneus (blue) masks on a mid-sagittal slice of the T1-weighted image. C The hippocampal (red) mask on a coronal slice of the T1-weighted image. The masks displayed in B and C were then resampled to the resolution of the M0 image

Fig. 2

White matter hyperintensity classification. Periventricular and deep white matter hyperintensities (WMHs). A T2-weighted FLAIR image for a representative participant is displayed in A. The periventricular mask (yellow) and deep mask (red) are overlaid on the T2-image in B

Fig. 3

Relationships between plasma S100b and cognition. Regression plots for plasma S100B with memory (A) and executive function (B). Covariates in both models included age, sex, and education. Z-scored values are reported in the figures

Fig. 4

Plasma S100b × parietal k_w moderation effect for episodic memory performance. Plots for S100B and memory at high (purple circle), mid (red triangle), and low (black star) levels of the moderator (parietal lobe k_w). Plots were created using the pick-a-point method, where low, mid, and high values represent 1 standard deviation below the mean, the mean, and 1 standard deviation above the mean of parietal lobe k_w, respectively. The memory composite was z-scored. S100b was mean centered prior to analyses and is reported in pg/mL. *p < .05

Fig. 5

Plasma S100b × deep white matter hyperintensity moderation effect for episodic memory performance. Plots for plasma S100B and memory at low (black star), mid (red triangle), and high (purple circle) levels of the moderator (deep white matter hyperintensities). Plots were created using the pick-a-point method, where low, mid, and high values represent 1 standard deviation below the mean, the mean, and 1 standard deviation above the mean for deep white matter hyperintensities, respectively. The memory composite was z-scored. S100B was mean centered prior to analyses and is reported in pg/mL. *p < .05