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.