Blood–brain barrier leakage at baseline and cognitive decline in cerebral small vessel disease: a 2-year follow-up study

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.