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

Abstract

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

N-Terminal Pro–B-Type Natriuretic Peptide and Subclinical Brain Damage in the General Population

“…Although several studies have shown cardiac dysfunction is associated with stroke and dementia, only a few studies have addressed the link between NT-proBNP level and markers of subclinical brain damage. We found that higher NT-proBNP level was associated with smaller total brain volume and gray matter volume, a finding that was in line with findings of the Age Gene/ Environment Susceptibility-Reykjavik Study on community-dwelling elderly persons (27). A study of Framingham offspring who had not experienced a stroke found no association between B-type natriuretic peptide level and parenchymal volumes (28).…”

N-Terminal Pro-B-Type Natriuretic Peptide and Risk of Future Cognitive Impairment in the REGARDS Cohort

“…In 4,029 older community-dwelling adults in Iceland, NT-proBNP was inversely associated with memory, processing speed and executive functioning, as well as lower brain volumes by magnetic resonance imaging; the associations with executive function and processing speed were independent of cardiac output [26].…”

“…Two biomarker discovery studies reported that NT-proBNP was associated with cognitive disorders [24,25]. In one study, among 147 biomarkers, apoE genotype and NTproBNP were primary contributors to improved specificity for a diagnosis of Alzheimer's Disease, but NT-proBNP was not associated with apoE genotype [25], contrary to findings here.In 4,029 older community-dwelling adults in Iceland, NT-proBNP was inversely associated with memory, processing speed and executive functioning, as well as lower brain volumes by magnetic resonance imaging; the associations with executive function and processing speed were independent of cardiac output [26].We are aware of four prospective studies on this topic. In the Alzheimer's Disease Neuroimaging Initiative, biomarker panels including NT-proBNP did not distinguish progression from mild cognitive impairment to Alzheimer's disease over 2 years [27].…”

Blood-based biomarkers in Alzheimer’s disease: an overview on proteomic and lipidomic approaches

“…The Gene/Environment Susceptibility (AGES)-Reykjavik Study analysed measured the NT-proBNP serum levels in over 4000 elderly individuals. Results show that high levels of serum NT-proBNP are independently linked with structural and functional alterations of the brain (18).…”