Blood biomarkers of vascular dysfunction in small vessel disease progression: Insights from a longitudinal neuroimaging study

Abstract

Introduction: This study explored the relationship between blood biomarkers of cerebrovascular function and small vessel disease (SVD) neuroimaging markers and cognitive outcomes in highly-phenotyped participants.

Methods: We conducted cross-sectional and 1-year longitudinal analyses on 181 patients with mild ischemic stroke, enriched for SVD features. We examined relationships between a panel of 13 blood biomarkers and magnetic resonance imaging (MRI) markers of SVD (structural lesions, diffusion-weighted imaging [DWI]-positive lesions, blood-brain barrier (BBB) permeability, and cerebrovascular reactivity (CVR), and cognition.

Results: In linear mixed models, vascular endothelial growth factor was significantly associated with incident DWI-positive lesions over 1 year. Intercellular adhesion molecule-1 was linked with lower CVR while platelet-derived growth factor-subunit B and Endothelin-1 were associated with higher CVR. Platelet-Selectin levels were associated with mild cognitive impairment at 1 year.

Discussion: Our results support the role of endothelial and pericyte dysfunction in SVD burden and progression and suggest that specific biomarkers relate to distinct SVD manifestations.

Highlights: Small vessel disease (SVD) lacks specific or predictive biomarker signatures. Vascular endothelial growth factor levels were linked to incident lesions detected over 1 year. Circulating intercellular adhesion molecule-1 related to lower cerebrovascular reactivity. Platelet-selectin levels were associated with mild cognitive impairment longitudinally. These findings could help stratify patients at high-risk of rapid-progression SVD.

Keywords: biomarkers; blood‐brain barrier; cerebrovascular dysfunction; cerebrovascular reactivity; cognitive impairment; endothelial dysfunction; pericyte; small vessel disease; vascular dementia.