Blood‐brain barrier failure as a core mechanism in cerebral small vessel disease and dementia: evidence from a cohort study

Wardlaw, Joanna M.; Makin, Stephen; Hernández, Maria C. Valdés; Armitage, Paul A.; Heye, Anna K.; Chappell, Francesca M; Maniega, Susana Muñoz; Sakka, Eleni; Shuler, Kirsten; Dennis, Martin; Thrippleton, Michael J.

doi:10.1016/j.jalz.2016.09.006

Cited by 200 publications

(249 citation statements)

References 59 publications

Supporting

Mentioning

224

Contrasting

Unclassified

Order By: Relevance

“…The predictors of this textural change were SVD indicators previously related to subtle BBB dysfunction: age, hypertension and WMH burden represented by Fazekas scores (6, 33, 35, 53). Given the limitations of the existing DCE-MRI protocols for assessing BBB permeability without knowledge of vessel surface area (8, 9) alternative methods for assessing pre–post gadolinium differences as markers of leakage are worth pursuing.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Application of Texture Analysis to Study Small Vessel Disease and Blood–Brain Barrier Integrity

et al. 2017

Self Cite

View full text Add to dashboard Cite

ObjectivesWe evaluate the alternative use of texture analysis for evaluating the role of blood–brain barrier (BBB) in small vessel disease (SVD).MethodsWe used brain magnetic resonance imaging from 204 stroke patients, acquired before and 20 min after intravenous gadolinium administration. We segmented tissues, white matter hyperintensities (WMH) and applied validated visual scores. We measured textural features in all tissues pre- and post-contrast and used ANCOVA to evaluate the effect of SVD indicators on the pre-/post-contrast change, Kruskal–Wallis for significance between patient groups and linear mixed models for pre-/post-contrast variations in cerebrospinal fluid (CSF) with Fazekas scores.ResultsTextural “homogeneity” increase in normal tissues with higher presence of SVD indicators was consistently more overt than in abnormal tissues. Textural “homogeneity” increased with age, basal ganglia perivascular spaces scores (p < 0.01) and SVD scores (p < 0.05) and was significantly higher in hypertensive patients (p < 0.002) and lacunar stroke (p = 0.04). Hypertension (74% patients), WMH load (median = 1.5 ± 1.6% of intracranial volume), and age (mean = 65.6 years, SD = 11.3) predicted the pre/post-contrast change in normal white matter, WMH, and index stroke lesion. CSF signal increased with increasing SVD post-contrast.ConclusionA consistent general pattern of increasing textural “homogeneity” with increasing SVD and post-contrast change in CSF with increasing WMH suggest that texture analysis may be useful for the study of BBB integrity.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Although the cause of cerebral SVD is unknown, increasing evidence indicates that the microvessel endothelium, i.e., the blood–brain barrier (BBB), plays a key role in SVD pathogenesis (2–6). …”

Section: Introductionmentioning

confidence: 99%

Application of Texture Analysis to Study Small Vessel Disease and Blood–Brain Barrier Integrity

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Higher WMHs and increased BBB permeability are associated with poor functional outcomes in CSVD patients . The impairment of the BBB predicts cognitive impairment at one year . Previous studies of BBB permeability in CSVD have focused on tight junction proteins, such as zonula occludens‐1 (ZO‐1), occludin, and claudin‐5 .…”

Section: Discussionmentioning

confidence: 99%

“…40 The impairment of the BBB predicts cognitive impairment at one year. 41 Previous studies of BBB permeability in CSVD have focused on tight junction proteins, such as zonula occludens-1 (ZO-1), occludin, and claudin-5. 42,43 The decreased expression of claudin-5, the key tight junction protein of the BBB, has been reported in a CSVD model.…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide riboside rescues angiotensin II–induced cerebral small vessel disease in mice

Chen

Wang

et al. 2020

CNS Neurosci Ther

View full text Add to dashboard Cite

Aims Hypertension is a leading cause of cerebral small vessel disease (CSVD). Currently, treatments for CSVD are limited. Nicotinamide riboside (NR) can protect against vascular injury and cognitive impairment in neurodegenerative diseases. In this study, the protective effects of NR against angiotensin ‐ (Ang ‐)–induced CSVD were evaluated. Methods To explore the effects of NR in CSVD, C57BL/6 mice were infused with Ang ‐, and NR was added to the food of the mice for 28 days. Then, short‐term memory, blood‐brain barrier (BBB) integrity, and endothelial function were detected. Arteriole injury and glial activation were also evaluated. Results Our data showed that mice infused with Ang ‐ exhibited decreased short‐term memory function and BBB leakage due to decreased claudin‐5 expression and increased caveolae‐mediated endocytosis after 28 days. Furthermore, Ang ‐ decreased the expression of α‐smooth muscle actin (α‐SMA) and increased the expression of proliferating cell nuclear antigen (PCNA) in arterioles and decreased the expression of neurofilament 200 (NF200) and myelin basic protein (MBP) in the white matter. These CSVD‐related damages induced by Ang ‐ were inhibited by NR administration. Moreover, NR administration significantly reduced glial activation around the vessels. Conclusion Our results indicated that NR administration alleviated Ang ‐–induced CSVD by protecting BBB integrity, vascular remodeling, neuroinflammation, and white matter injury (WMI)–associated cognitive impairment.

show abstract

“…Moreover, a number of blood pressure parameters relevant to the brain have not been addressed systematically. Pulse pressure relates to arterial brain stiffness which in turn correlates with brain perfusion, which itself may be heterogenous requiring different blood pressure parameters. One of the strongest associations between hypertension and the brain relates to white matter changes (leukoaraiosis) that in turn represent harbingers of increased risk of stroke and dementia .…”

Section: Risk Factorsmentioning

confidence: 99%

Implementing the proclamation of stroke and potentially preventable dementias

Hachinski

Ganten

Lackland

et al. 2018

J of Clinical Hypertension

View full text Add to dashboard Cite

Brain health plays a central role in well‐being and in the management of chronic diseases. Stroke and dementia pose the two greatest threats to brain health, but recent developments suggest the possibility that preventing stroke may also prevent some dementias: (a) A large population study showed a 32% decrease in the incidence of stroke and a concomitant 7% reduction in the incidence of dementia; (b) the treatment of atrial fibrillation resulted not only in stroke reduction, but also a 48% decrease in dementia; (c) the hypothesis‐free analyses have shown that the first phase of Alzheimer disease involves vascular dysregulation, opening the door to new therapeutic approaches; (d) cognitive impairment, often treatable and reversible, accompanies heart and kidney failure. These developments, combined with the knowledge that stroke, dementia, and heart disease share the same major treatable risk factors, particularly hypertension, offer an opportunity for their joint prevention. This aspiration is expressed by a Proclamation of the World Stroke Organization on Stroke and Potentially Preventable Dementias and endorsed by the World Heart Federation, the World Hypertension League, Alzheimer Disease International, and 18 other international, regional, and national organizations as a call for action.

show abstract

Blood‐brain barrier failure as a core mechanism in cerebral small vessel disease and dementia: evidence from a cohort study

Cited by 200 publications

References 59 publications

Application of Texture Analysis to Study Small Vessel Disease and Blood–Brain Barrier Integrity

Application of Texture Analysis to Study Small Vessel Disease and Blood–Brain Barrier Integrity

Nicotinamide riboside rescues angiotensin II–induced cerebral small vessel disease in mice

Implementing the proclamation of stroke and potentially preventable dementias

Contact Info

Product

Resources

About