Zhang Wei, Zhou Xia, Yin Jiabin, Zhao Wenming, Huang Chaojuan, Zhang Cun, Wan Ke, Li Mingxu, Zhu Xiaoqun, Sun Zhongwu
Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China; Research Center of Clinical Medical Imaging, Anhui Province, Hefei 230032, China.
Brain Res. 2023 May 15;1807:148318. doi: 10.1016/j.brainres.2023.148318. Epub 2023 Mar 8.
YKL-40 is a novel neuroinflammatory marker associated with white matter damage and cognitive dysfunction. 110 CSVD patients, including 54 with mild cognitive impairment (CSVD-MCI), 56 with no cognitive impairment (CSVD-NCI), and 40 healthy controls (HCs) underwent multimodal magnetic resonance examination, serum YKL-40 level detection and cognitive function assessment to investigate the association between YKL-40 and white matter damage and cognitive impairment in cerebral small vessel disease (CSVD) patients. White matter hyperintensities volume was calculated using the Wisconsin White Matter Hyperintensity Segmentation Toolbox (W2MHS) for white matter macrostructural damage evaluation. For white matter microstructural damage evaluation, fractional anisotropy (FA) and mean diffusivity (MD) indices of the region of interest were analyzed based on diffusion tensor imaging (DTI) images using the Tract-Based Spatial Statistics (TBSS) pipeline. The serum YKL-40 level of CSVD was significantly higher than those of HCs, and the CSVD-MCI was higher than in HCs and CSVD-NCI. Furthermore, serum YKL-40 provided high diagnostic accuracy for CSVD and CSVD-MCI. The macroscopic and microstructure of white matter in CSVD-NCI and CSVD-MCI patients indicated different degrees of damage. Disruption of white matter macroscopic and microstructure was significantly associated with YKL-40 levels and cognition deficits. Moreover, the white matter damage mediated the associations between the increased serum YKL-40 levels and cognitive impairment. Our findings demonstrated that YKL-40 might be a potential biomarker of white matter damage in CSVD, whereas white matter damage was associated with cognitive impairment. Serum YKL-40 measurement provides complementary information regarding the neural mechanism of CSVD and its associated cognitive impairment.
YKL-40是一种与白质损伤和认知功能障碍相关的新型神经炎症标志物。110例脑小血管病（CSVD）患者，包括54例轻度认知障碍患者（CSVD-MCI）、56例无认知障碍患者（CSVD-NCI）和40例健康对照者（HCs）接受了多模态磁共振检查、血清YKL-40水平检测和认知功能评估，以研究YKL-40与CSVD患者白质损伤和认知障碍之间的关联。使用威斯康星白质高信号分割工具箱（W2MHS）计算白质高信号体积，以评估白质宏观结构损伤。对于白质微观结构损伤评估，基于扩散张量成像（DTI）图像，使用基于纤维束的空间统计学（TBSS）流程分析感兴趣区域的分数各向异性（FA）和平均扩散率（MD）指数。CSVD患者的血清YKL-40水平显著高于HCs，且CSVD-MCI患者的血清YKL-40水平高于HCs和CSVD-NCI患者。此外，血清YKL-40对CSVD和CSVD-MCI具有较高的诊断准确性。CSVD-NCI和CSVD-MCI患者白质的宏观和微观结构均显示出不同程度的损伤。白质宏观和微观结构的破坏与YKL-40水平和认知缺陷显著相关。此外，白质损伤介导了血清YKL-40水平升高与认知障碍之间的关联。我们的研究结果表明，YKL-40可能是CSVD中白质损伤的潜在生物标志物，而白质损伤与认知障碍相关。血清YKL-40测量为CSVD及其相关认知障碍的神经机制提供了补充信息。
