Blood\u2013brain barrier leakage in relation to white matter hyperintensity volume and cognition in small vessel disease and normal aging

C Eleana Zhang,Jacobus F A Jansen,Cécile R L P N Jeukens,Julie Staals,Robert J Van Oostenbrugge,Renske Uiterwijk,Sau May Wong,Walter H Backes

doi:10.1007/s11682-018-9855-7

C Eleana Zhang, Jacobus F A Jansen + Show 6 more

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https://doi.org/10.1007/s11682-018-9855-7

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Abstract

Blood–brain barrier (BBB) leakage increases with age and is involved in the pathophysiology of cerebral small vessel disease (cSVD). We examined the relationship between BBB leakage and white matter hyperintensity (WMH) volume and cognition, in cSVD patients and healthy controls. Seventy-seven patients with clinically overt cSVD and thirty-nine age matched healthy controls underwent dynamic contract-enhanced and structural brain MRI and neuropsychological assessment. We quantified BBB leakage volume and rate in normal appearing white matter (NAWM), WMH and cortical grey matter (CGM). Larger leakage volume and lower leakage rate in WMH were associated with larger WMH volume in cSVD but not in controls. Higher leakage rate in NAWM was associated with lower scores on executive function and information processing speed in healthy controls, whereas no relation with cognition was found in cSVD patients. Our findings support the involvement of BBB leakage in cSVD and aging. They also suggest that the mechanism of cognitive dysfunction in cSVD is more complex and multifactorial in cSVD compared with normal aging.

Highlights

Blood–brain barrier (BBB) permeability increases with age and dysfunction of the BBB is thought to be an important pathophysiological mechanism in cerebral small vessel disease (Skoog et al 1998; Wardlaw et al 2003). cSVD is an age and vascular risk factors related disorder of the small vessels of the brain, and can cause debilitatingElectronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Macroscopically visible lesions such as white matter hyperintensities (WMH) may occur with increasing age and in the absence of cerebral vascular diseases
In patients with cSVD, higher vL and lower Ki in WMH was significantly associated with a larger WMH volume (Table 2)
In this study on patients with clinically overt cSVD and ageand sex- matched healthy controls, we examined the association between BBB leakage and cognitive performance as well as WMH volume

Summary

Introduction

Blood–brain barrier (BBB) permeability increases with age and dysfunction of the BBB is thought to be an important pathophysiological mechanism in cerebral small vessel disease (cSVD) (Skoog et al 1998; Wardlaw et al 2003). Visible lesions such as white matter hyperintensities (WMH) may occur with increasing age and in the absence of cerebral vascular diseases. Higher BBB leakage has been associated with increasing WMH load in healthy older subjects (Farrall and Wardlaw 2009; Skoog et al 1998). No association was found between BBB leakage and WMH volume in patients with VCI (Huisa et al 2015). In patients with mild stroke, BBB leakage in the NAWM

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