Increase of blood-brain barrier leakage is related to cognitive decline in vascular mild cognitive impairment

Abstract

Background Blood-brain barrier (BBB) breakdown, as an early biomarker for vascular mild cognitive impairment (vMCI), has only been validated by a few studies. The aim of this study was to investigate whether compromised BBB integrity is involved in vMCI patients, and detect the relationship between BBB breakdown and cognitive function. BBB leakage in vMCI was explored, and the relationship between BBB leakage and cognitive function was discussed in this study. Methods This is a cross-sectional study involving 26 vMCI patients and 21 sex- and age-matched healthy controls. Dynamic contrast-enhanced-magnetic resonance imaging was performed for all participants, to determine BBB leakage. Leakage volume, leakage rate, and fractional blood plasma volume (Vp) in the grey and white matter were evaluated. Neuropsychological tests were used to determine cognitive function. Leakage rate, leakage volume, and Vp in different brain locations, including deep grey matter, cortical grey matter, white matter hyperintensity, and normal-appearing white matter were compared between the two groups. Results Multivariable linear regression analyses revealed that in all regions of interest, the leakage rate was significantly higher in vMCI patients relative to controls. Leakage volume in normal-appearing white matter and white matter hyperintensity were significantly higher, while Vp in normal-appearing white matter, deep grey matter, and cortical grey matter were significantly lower in vMCI patients. Moreover, Montreal Cognitive Assessment scores decreased with the increase of leakage rate in white matter hyperintensity. Conclusion Increased BBB permeability was detected in vMCI patients and was related to cognitive decline, which suggested that BBB breakdown might be involved in cognitive dysfunction pathogenesis.

Retinal Vasculopathy in Alzheimer’s Disease

“…Vascular pathology in AD is an expanding subject and a growing number of studies show that vascular-related damage in the brain and retina can predict cognitive decline ( Vidal and Mavet, 1989 ; Baker et al, 2007 ; Gharbiya et al, 2014 ; Boyle et al, 2015 ; Bulut et al, 2016 , 2018 ; Cunha et al, 2017 ; McGrory et al, 2017 ; Planton et al, 2017 ; Cabrera DeBuc et al, 2018 ; Deal et al, 2018 ; Jiang et al, 2018 ; O’Bryhim et al, 2018 ; van der Flier et al, 2018 ; Iadecola et al, 2019 ; Jung et al, 2019 ; Montagne et al, 2020 ; Shi et al, 2020a ; Li et al, 2021 ). Cerebral vascular damage such as ischemia leads to disturbed nutrient supply, induces oxidative stress and inflammatory activities, impedes Aβ clearance and/or alters amyloid-processing enzymes ( Marchesi, 2011 ), all of which can contribute to neurodegeneration and cognitive decline.…”

Extracellular to Intracellular Body Water and Cognitive Function among Healthy Older and Younger Adults

“…Mooijaart and colleagues found an association between attention/executive function and systemic inflammatory biomarkers, but they did not find an association between working or episodic memory and inflammation [ 35 ]. Li and colleagues reported that patients diagnosed with mild vascular cognitive impairment showed diminished information processing speed, attention, executive function, spatial function, and language function but no measurable change in memory [ 36 ]. Hence, it may be that our healthy group of older people with the highest extracellular/intracellular water ratios, who performed poorer on the Flanker test of executive function and attention, are demonstrating early changes in cognitive performance.…”

“…Pathology to the vascular system appears to be a primary path to impaired cognitive function. Leakage of blood plasma through the blood–brain barrier is believed to contribute to even mild cognitive impairment [ 36 ]. This leakage through the blood–brain barrier is measurable through imaging of the hippocampus of the brain and is tightly coupled with cognitive status [ 36 ].…”

The Evolving Concept of Neuro-Thromboinflammation for Neurodegenerative Disorders and Neurotrauma: A Rationale for PAR1-Targeting Therapies

“…Numerous authors have published extensively on BBB dysfunction in AD [ 92 , 93 , 94 , 95 , 96 ]. In addition, a long history of BBB dysfunction in ALS patients had been previously reviewed [ 97 ]; however, in the “modern era”, Garbuzova-Davis and colleagues at the University of South Florida began to study BBB integrity in transgenic SOD1 mice in the early 2000s, finding evidence of BBB and blood–spinal cord barrier (BSCB) dysfunction both in this ALS model as well as in patients with ALS [ 98 , 99 , 100 ].…”