Jaime Garcia Daniela, Clancy Una, Arteaga Carmen, Valdés-Hernandez Maria C, Chappell Francesca M, Jochems Angela C C, Cheng Yajun, Zhang Junfang, Thrippleton Michael J, Stringer Michael S, Sleight Emilie, Backhouse Ellen V, Wiseman Stewart, Brown Rosalind, Doubal Fergus N, Montagne Axel, Wardlaw Joanna M
Centre for Clinical Brain Sciences, School of Clinical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, UK.
UK Dementia Research Institute at the University of Edinburgh, Edinburgh, UK.
Alzheimers Dement. 2025 Apr;21(4):e70152. doi: 10.1002/alz.70152.
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.
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.
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.
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.
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.
本研究在具有高度表型特征的参与者中，探讨了脑血管功能血液生物标志物与小血管疾病（SVD）神经影像标志物及认知结果之间的关系。
我们对181例具有SVD特征的轻度缺血性卒中患者进行了横断面和为期1年的纵向分析。我们检查了一组13种血液生物标志物与SVD的磁共振成像（MRI）标志物（结构性病变、弥散加权成像[DWI]阳性病变、血脑屏障[BBB]通透性和脑血管反应性[CVR]）以及认知之间的关系。
在线性混合模型中，血管内皮生长因子与1年内发生的DWI阳性病变显著相关。细胞间黏附分子-1与较低的CVR相关，而血小板衍生生长因子亚基B和内皮素-1与较高的CVR相关。血小板选择素水平与1年后的轻度认知障碍相关。
我们的结果支持内皮细胞和周细胞功能障碍在SVD负担和进展中的作用，并表明特定的生物标志物与不同的SVD表现相关。
小血管疾病（SVD）缺乏特异性或预测性生物标志物特征。血管内皮生长因子水平与1年内检测到的新发病变有关。循环细胞间黏附分子-1与较低的脑血管反应性相关。血小板选择素水平纵向与轻度认知障碍相关。这些发现有助于对SVD快速进展高危患者进行分层。
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