Abstract
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.
Highlights
Cerebral small vessel disease is an umbrella term that covers several pathologies involving the small vessels in the brain with various etiologies [1]
In patients with clinically overt Cerebral small vessel disease (cSVD), we found that both higher baseline blood–brain barrier (BBB) leakage volume and leakage rate in white and grey matter structures are associated with stronger overall cognitive decline
The BBB is thought to play a pivotal role in the pathogenesis of cSVD and disease progression [5, 7, 8, 10]
Summary
Cerebral small vessel disease (cSVD) is an umbrella term that covers several pathologies involving the small vessels in the brain with various etiologies [1]. The underlying pathophysiological mechanism of cSVD remains largely unclear, dysfunction of the blood–brain barrier (BBB) is thought to be one of the initiating factors [2]. The neurovascular unit (NVU) regulates the close relationship between the BBB and the brain parenchyma [3]. The BBB plays a critical role in maintaining brain homeostasis by regulating the influx of nutrients from the bloodstream, controlling the efflux of wastes and protecting the brain cells from blood constituents by forming a physical barrier [3, 4]. In cSVD, it is thought that dysfunction of the cerebral microvascular endothelium
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
