Cardiac Output as a Potential Risk Factor for Abnormal Brain Aging

Jefferson, Angela L.

doi:10.3233/jad-2010-100081

Cited by 92 publications

(84 citation statements)

References 77 publications

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“…Importantly, the brain is known to possess an autoregulatory mechanism for maintaining CBF; however, conditions resulting in reduced cardiac output can overwhelm the CNS autoregulatory mechanism. The diabetic cardiomyopathy observed in CRS and T2DM may be associated with cognitive impairment, dementias, and DC due to direct myocardial dysfunction, decreased cardiac output, hypoperfusion, and the associated decreased cerebral perfusion and CBF [48,49,50]. …”

Section: Cardiac and Renal Contributions To DCmentioning

confidence: 99%

Cardiorenal Metabolic Syndrome and Diabetic Cognopathy

et al. 2013

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The prevalence of the cardiorenal metabolic syndrome (CRS) is increasing in parallel with obesity, type 2 diabetes mellitus, Alzheimer's disease, and other forms of dementia. Along with metabolic, inflammatory, and immunological abnormalities, there is maladaptive structural remodeling of the heart, kidney, and brain. The term ‘diabetic cognopathy' (DC) may be used when discussing functional and structural changes in the brain of the diabetic patient. DC likely represents an advanced form of these changes in the brain that evolve with increasing duration of the CRS and subsequent clinical diabetes. We posit that DC develops due to a convergence of aging, genetic and lifestyle abnormalities (overnutrition and lack of exercise), which result in multiple injurious metabolic and immunologic toxicities such as dysfunctional immune responses, oxidative stress, inflammation, insulin resistance, and dysglycemia (systemically and in the brain). These converging abnormalities may lead to endothelial blood-brain barrier tight junction/adherens junction (TJ/AJ) complex remodeling and microglia activation, which may result in neurodegeneration, impaired cognition, and dementia. Herein, we describe the brain ultrastructural changes evolving from a normal state to maladaptive remodeling in rodent models of CRS including microglia activation/polarization and attenuation and/or loss of the TJ/AJ complexes, pericytes and astrocytes of the neurovascular unit. Further, we discuss the potential relationship between these structural changes and the development of DC, potential therapeutic strategies, and future directions.

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Section: Cardiac and Renal Contributions To DCmentioning

confidence: 99%

Cardiorenal Metabolic Syndrome and Diabetic Cognopathy

et al. 2013

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“…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. 12,13 Most extant studies investigating this association are based on patient populations and no population-based cohort study of older individuals comprehensively evaluated the association of NT-proBNP with structural and functional features of abnormal brain aging.…”

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confidence: 99%

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

et al. 2015

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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

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“…Regional brain activity levels may be inferred by detecting rapid changes in blood oxygenation levels (BOLD) which are presumed to reflect neuronal and associated tissue metabolic responses to stimulation [134]. Recent analyses have revealed an association between intracranial atherosclerosis and LOAD dementia [3-10], and significant correlations between neuropathology and cognition and cardiovascular disease as well as with age-associated cardiovascular performance decline [135][136][137][138][139][140][141][142][143][144]. Observations of LOAD subject brain activities reveal marked region-specific metabolic reductions compared to subjects without dementia suggesting both baseline perfusion level declines as well as a loss of surge capacity in response to stimulation [145][146][147][148][149].…”

Section: Cardiovascular Dysfunction and Diabetes In Ad Pathogenesismentioning

confidence: 99%

Alzheimer’s disease syndrome – Recognizing the complexity of dementia

Kokjohn¹,

Serrano²

2017

Neurol Disord Therap

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Therapies designed to disrupt amyloid plaque deposits or prevent their formation have yielded disappointing results against cognitive failure, suggesting that both our mechanistic models of dementia and interventions must become more nuanced. These treatments targeted Aβ40/42, but the amyloid accumulated in Alzheimer's disease patients is modified extensively and far more structurally diverse. Despite intensive work, the structure and physical state of the most toxic amyloid species remains mysterious. In addition, multiple lines of evidence suggest the genesis and progression of dementia is more complicated than the accumulation of senile plaques beyond a tolerable threshold. If amyloid plays key, but non-exclusive, roles in dementia pathogenesis this hypothesis must be addressed through investigations that are more holistic in scope. New imaging methods provide investigators unprecedented capabilities to detect and classify neuropathology in living subjects. Interpreting future clinical trial outcomes will hinge on correlating effects against dementia in subject cohorts that are precisely differentiated with respect to neuropathology and neurochemistry. Improving understanding of the comorbidities and the environmental/lifestyle factors foreshadowing cognitive failure will aid in the interpretation of clinical trials. Most important, as we seek an elusive cure for AD, these findings may be rapidly translatable into concrete and achievable public health improvements.

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Cardiac Output as a Potential Risk Factor for Abnormal Brain Aging

Cited by 92 publications

References 77 publications

Cardiorenal Metabolic Syndrome and Diabetic Cognopathy

Cardiorenal Metabolic Syndrome and Diabetic Cognopathy

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

Alzheimer’s disease syndrome – Recognizing the complexity of dementia

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