Blood–brain barrier (BBB) dysfunction is one of the pathophysiological mechanisms in cerebral small vessel disease (SVD). Previously, it was shown that BBB leakage volume is larger in patients with SVD compared with controls. In this study, we investigated the link between BBB leakage and cognitive decline over 2 years in patients with cSVD. At baseline, 51 patients with clinically overt cSVD (lacunar stroke or mild vascular cognitive impairment) received a dynamic contrast-enhanced MRI scan to quantify BBB permeability in the normal-appearing white matter (NAWM), white matter hyperintensities (WMH), cortical grey matter (CGM), and deep grey matter (DGM). Cognitive function in the domain executive function, information processing speed, and memory was measured in all patients at baseline and after 2 years. The association between baseline BBB leakage and cognitive decline over 2 years was determined with multivariable linear regression analysis, corrected for age, sex, educational level, baseline WMH volume, and baseline brain volume. Regression analyses showed that higher baseline leakage volume and rate in the NAWM and CGM were significantly associated with increased overall cognitive decline. Furthermore, higher baseline leakage volume in the NAWM and CGM, and higher baseline leakage rate in the CGM were significantly associated with increased decline in executive function. This longitudinal study showed that higher BBB leakage at baseline is associated with stronger cognitive decline, specifically in executive function, over 2 years of follow-up in patients with cSVD. These results emphasize the key role of BBB disruption in the pathophysiology and clinical progression of cSVD.

血脑屏障（BBB）功能障碍是脑小血管病（SVD）的病理生理机制之一。以前的研究表明，与对照组相比，SVD 患者的 BBB 渗漏量更大。在这项研究中，我们调查了 cSVD 患者 2 年内 BBB 渗漏与认知能力下降之间的联系。在基线时，51 名临床明显 cSVD（腔隙性中风或轻度血管性认知障碍）的患者接受了动态对比增强 MRI 扫描，以量化外观正常的白质 (NAWM)、白质高信号 (WMH)、皮质灰质中的 BBB 通透性物质 (CGM) 和深灰质 (DGM)。在基线和 2 年后测量了所有患者的域执行功能、信息处理速度和记忆的认知功能。基线 BBB 渗漏与 2 年认知能力下降之间的关联是通过多变量线性回归分析确定的，校正了年龄、性别、教育水平、基线 WMH 容量和基线脑容量。回归分析表明，NAWM 和 CGM 中较高的基线渗漏量和速率与整体认知能力下降的增加显着相关。此外，NAWM 和 CGM 中较高的基线渗漏量以及 CGM 中较高的基线渗漏率与执行功能下降的增加显着相关。这项纵向研究表明，在 cSVD 患者的 2 年随访中，基线时较高的 BBB 泄漏与更强的认知能力下降有关，特别是在执行功能方面。