Higher blood–brain barrier permeability is associated with higher white matter hyperintensities burden

Abstract

The pathogenesis of white matter hyperintensities (WMH) is incompletely understood but blood-brain barrier (BBB) dysfunction may play a key role. This study aimed to investigate the relationship between BBB permeability and the severity of WMH burden. Consecutive participants without symptomatic stroke history presented for physical examination were recruited in this cross-sectional study and divided into three WMH burden groups according to total Fazekas scores. They received dynamic contrast-enhanced-magnetic resonance imaging to measure BBB permeability, and received Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). A total of 102 participants aged 49-90 years (mean age of 69.82 years) were enrolled (36 with low WMH burden, 35 with medium WMH burden, and 31 with high WMH burden). Multivariable linear regression analyses revealed that participants with higher WMH burden had significantly higher BBB leakage rate and area under the leakage curve in normal-appearing white matter, WMH, cortical gray matter, and deep gray matter (DGM) after adjustment for age, sex, and vascular risk factors. Scores on MMSE and MoCA decreased with increasing leakage rate in WMH and DGM after adjustment for age, sex, WMH burden, and education years. We found that higher BBB permeability is associated with higher WMH burden and cognitive decline. The compromised BBB integrity may be a critical contributor to the pathogenesis of WMH and part of a series of pathological processes that finally lead to cognitive impairment.

Cardiovascular disease and brain health: Focus on white matter hyperintensities

“…Subsequent reports focused on chronic edema due to a primary blood brain barrier dysfunction [ 8 ], which is supported by the evidence of increased albumin concentration within the interstitial space [ 14 ]. Indeed, more recent clinical data on dynamic MRI demonstrated increased gadolinium leakage into WMH, supporting in vivo the hypothesis of increased blood brain barrier permeability [ 15 ]. Interestingly, however, no disruption of endothelial tight junctions has been proven [ 14 ], yet endothelial cells were shown to express markers of activation [ 16 ].…”

Compromised Blood–Brain Barrier Integrity Is Associated With Total Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease

“…Dynamic contrast-enhanced (DCE)-MRI combined with an appropriate pharmacokinetics model is a reliable method to quantitatively evaluate BBB permeability ( 5 ). Using DCE-MRI method, previous cross-sectional studies reported compromised BBB integrity in patients with lacunar stroke, WMH, and mild vascular cognitive impairment (mVCI) ( 6 – 10 ). Moreover, a longitudinal study ( 11 ) revealed the association between poor functional outcome and increased BBB permeability in cSVD patients.…”

Endothelial-derived exosomes demonstrate a link between endothelial innate inflammation and brain dysfunction and injury in aging

“…In addition, higher load of WMH is associated with adverse age-associated cognitive outcomes, such as slowed processing speed and increased risk of AD dementia 40,41 . In the absence of frank neurodegenerative phenotypes, age-associated WMH is frequently presumed secondary to cerebral vascular endotheliopathies resulting in increased BBB leakage and activation of CNS immune system, leading to reactive gliosis 40,[42][43][44][45] . In this model, endothelial cells play a central role.…”