The heart-brain connection: mechanistic insights and models

Ritz, Katja; Buchem, Mark A. van; Daemen, Mat J.A.P.

doi:10.1007/s12471-012-0348-9

Cited by 33 publications

(24 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Brain hypoperfusion is 1 of 2 major mechanisms underlying development of cognitive impairment . Therefore, we compared resting CBF in the cortex, hippocampus, and thalamus in 10‐month‐old Tgαq*44 (n=6) and FVB mice (n=7) (Figure A) using in vivo magnetic resonance imaging.…”

Section: Resultsmentioning

confidence: 99%

Vascular Cognitive Impairment Linked to Brain Endothelium Inflammation in Early Stages of Heart Failure in Mice

Adamski

Sternak

Mohaissen

et al. 2018

JAHA

View full text Add to dashboard Cite

BackgroundAlthough advanced heart failure (HF) is a clinically documented risk factor for vascular cognitive impairment, the occurrence and pathomechanisms of vascular cognitive impairment in early stages of HF are equivocal. Here, we characterize vascular cognitive impairment in the early stages of HF development and assess whether cerebral hypoperfusion or prothrombotic conditions are involved.Methods and ResultsTgαq*44 mice with slowly developing isolated HF triggered by cardiomyocyte‐specific overexpression of G‐αq*44 protein were studied before the end‐stage HF, at the ages of 3, 6, and 10 months: before left ventricle dysfunction; at the stage of early left ventricle diastolic dysfunction (with preserved ejection fraction); and left ventricle diastolic/systolic dysfunction, respectively. In 6‐ to 10‐month‐old but not in 3‐month‐old Tgαq*44 mice, behavioral and cognitive impairment was identified with compromised blood‐brain barrier permeability, most significantly in brain cortex, that was associated with myelin sheet loss and changes in astrocytes and microglia. Brain endothelial cells displayed increased E‐selectin immunoreactivity, which was accompanied by increased amyloid‐β1‐42 accumulation in piriform cortex and increased cortical oxidative stress (8‐OHdG immunoreactivity). Resting cerebral blood flow measured by magnetic resonance imaging in vivo was preserved, but ex vivo NO‐dependent cortical arteriole flow regulation was impaired. Platelet hyperreactivity was present in 3‐ to 10‐month‐old Tgαq*44 mice, but it was not associated with increased platelet‐dependent thrombogenicity.ConclusionsWe report for the first time that vascular cognitive impairment is already present in the early stage of HF development, even before left ventricle systolic dysfunction. The underlying pathomechanism, independent of brain hypoperfusion, involves preceding platelet hyperreactivity and brain endothelium inflammatory activation.

show abstract

Section: Resultsmentioning

confidence: 99%

Vascular Cognitive Impairment Linked to Brain Endothelium Inflammation in Early Stages of Heart Failure in Mice

Adamski

Sternak

Mohaissen

et al. 2018

JAHA

View full text Add to dashboard Cite

show abstract

“…The heart is the generator of the cerebral perfusion pressure and intra and extra-cranial vessels modify the cerebral perfusion as they deliver the blood to the brain 17 . Given the increasing prevalence of pathologies affecting the heart and cerebropetal arteries in the elderly, these pathologies can be expected to contribute to changes in the brain as people age.…”

Section: Discussionmentioning

confidence: 99%

Cardiac and Carotid Markers Link With Accelerated Brain Atrophy

Sabayan

Buchem

Sigurðsson

et al. 2016

ATVB

View full text Add to dashboard Cite

Objective Pathologies in the heart-brain axis might, independently or in combination, accelerate the process of brain parenchymal loss. We aimed to investigate the association of serum N-terminal brain natriuretic peptide (NT-proBNP), as a marker of cardiac dysfunction, and carotid intima media thickness (CIMT), as a marker of carotid atherosclerosis burden, with structural brain changes. Approach and Results In the longitudinal population-based AGES–Reykjavik Study, we included 2430 subjects (mean age 74.6, 41.4% male) with baseline data on NT-proBNP and CITM (assessed by Ultrasound imaging). Participants underwent a high-resolution brain MRI at baseline and five years later to assess total brain (TBV), grey matter (GMV) and white matter (WMV) volumes. Each unit higher log-transformed NT-proBNP was associated with 3.6 ml (95% CI: −6.0, −1.1) decline in TBV and 3.5 ml (95% CI: −5.7, −1.3) decline in GMV. Likewise, each millimeter higher CIMT was associated with 10.8 ml (95% CI: −17.3, −4.2) decline in TBV and 8.6 ml (95% CI: −14.4, −2.8) decline in GMV. There was no association between NT-proBNP and CIMT and changes in WMV. Compared to participants with low NT-proBNP and CIMT, participants with both high NT-proBNP and CIMT had 3.8 ml (95% CI: −6.0, −1.6) greater decline in their TBV and 4ml (95% CI: −6.0, −2.0) greater decline in GMW. These associations were independent of socio-demographic and cardiovascular factors. Conclusions Older subjects with both cardiac dysfunction and carotid atherosclerosis are at an increased risk for brain parenchymal loss. Accumulated pathologies in the heart-brain axis might accelerate brain atrophy.

show abstract

“…9 The heart provides a driving force for cerebral perfusion and acts in concert with the vessels in the heart-brain axis to ensure sufficient cerebral blood flow. 10 Hence, impaired cardiac function might be a risk factor for accelerating development of pathologies in the brain. 11 Recently, a limited number of studies investigated whether high NT-proBNP, as a marker for impaired cardiac function, is associated with impaired cognition.…”

mentioning

confidence: 99%

N-terminal pro–brain natriuretic peptide and abnormal brain aging

et al. 2015

View full text Add to dashboard Cite

Objective: To investigate the independent association of serum N-terminal fragment of the prohormone natriuretic peptide (NT-proBNP) with structural and functional features of abnormal brain aging in older individuals. Methods:In this cross-sectional study based on the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we included 4,029 older community-dwelling individuals (born 1907 to 1935) with a measured serum level of NT-proBNP. Outcomes included parenchymal brain volumes estimated from brain MRI, cognitive function measured by tests of memory, processing speed, and executive functioning, and presence of depressive symptoms measured using the Geriatric Depression Scale. In a substudy, cardiac output of 857 participants was assessed using cardiac MRI.Results: In multivariate analyses, adjusted for sociodemographic and cardiovascular factors, higher levels of NT-proBNP were independently associated with lower total (p , 0.001), gray matter (p , 0.001), and white matter (p 5 0.001) brain volumes. Likewise, in multivariate analyses, higher levels of NT-proBNP were associated with worse scores in memory (p 5 0.005), processing speed (p 5 0.001), executive functioning (p , 0.001), and more depressive symptoms (p 5 0.002). In the substudy, the associations of higher NT-proBNP with lower brain parenchymal volumes, impaired executive function and processing speed, and higher depressive symptoms were independent of the level of cardiac output.Conclusions: Higher serum levels of NT-proBNP, independent of cardiovascular risk factors and a measure of cardiac function, are linked with alterations in brain structure and function. Roles of natriuretic peptides in the process of brain aging need to be further elucidated. Brain natriuretic peptide (BNP) was first described in 1988 after isolation from porcine brain tissue.1 It was soon found that ventricular myocardium produces BNP, and thereafter, BNP has been regarded as a cardiac hormone.2 Upon release, BNP pro-hormone cleaves into the biologically active BNP hormone and the biologically inactive N-terminal fragment (NTproBNP).3 The main stimulus for BNP and NT-proBNP synthesis is myocardial wall stress, and currently these biomarkers are widely used for diagnosis and prognosis of heart failure. 4 Several reports showed that elevated levels of NT-proBNP not only predict higher risk of ischemic heart disease and cardiac arrhythmias but also cerebrovascular events.5-7 Recent evidence indicates that high NT-proBNP also associates with subclinical brain pathologies such as white matter hyperintensties. 8 The structural and functional integrity of the brain is dependent on an adequate supply of cerebral blood flow. 9

show abstract

The heart-brain connection: mechanistic insights and models

Cited by 33 publications

References 41 publications

Vascular Cognitive Impairment Linked to Brain Endothelium Inflammation in Early Stages of Heart Failure in Mice

Vascular Cognitive Impairment Linked to Brain Endothelium Inflammation in Early Stages of Heart Failure in Mice

Cardiac and Carotid Markers Link With Accelerated Brain Atrophy

N-terminal pro–brain natriuretic peptide and abnormal brain aging

Contact Info

Product

Resources

About