N-Terminal pro-Brain Natriuretic Peptide and Associations With Brain Magnetic Resonance Imaging (MRI) Features in Middle Age: The CARDIA Brain MRI Study.

Ian T Ferguson,Osorio Meirelles,Otto A Sanchez,Nick Bryan,Lenore J Launer,David R Jacobs,Martine Elbejjani,Behnam Sabayan,Russell Tracy

doi:10.3389/fneur.2018.00307

Abstract

As part of research on the heart-brain axis, we investigated the association of N-terminal pro-brain natriuretic peptide (NT-proBNP) with brain structure and function in a community-based cohort of middle-aged adults from the Brain Magnetic Resonance Imaging sub-study of the Coronary Artery Risk Development in Young Adults (CARDIA) Study. In a cohort of 634 community-dwelling adults with a mean (range) age of 50.4 (46-52) years, we examined the cross-sectional association of NT-proBNP to total, gray (GM) and white matter (WM) volumes, abnormal WM load and WM integrity, and to cognitive function tests [the Digit Symbol Substitution Test (DSST), the Stroop test, and the Rey Auditory-Verbal Learning Test]. These associations were examined using linear regression models adjusted for demographic and cardiovascular risk factors and cardiac output. Higher NT-proBNP concentration was significantly associated with smaller GM volume (β = -3.44; 95% CI = -5.32, -0.53; p = 0.003), even after additionally adjusting for cardiac output (β = -2.93; 95% CI = -5.32, -0.53; p = 0.017). Higher NT-proBNP levels were also associated with lower DSST scores. NT-proBNP was not related to WM volume, WM integrity, or abnormal WM load. In this middle-aged cohort, subclinical levels of NT-proBNP were related to brain function and specifically to GM and not WM measures, extending similar findings in older cohorts. Further research is warranted into biomarkers of cardiac dysfunction as a target for early markers of a brain at risk.

Highlights

Several studies suggest a role for cardiac health in processes relating to brain atrophy and cognitive impairment at older age, leading to hypotheses concerning the heart–brain axis [1,2,3,4]
We investigated the association of NT-proBNP to several magnetic resonance imaging (MRI) measures that have been linked to neurocognitive pathology, including total brain volume, gray matter (GM) volume, white matter (WM) volume, abnormal WM load, and WM microstructural integrity in a well characterized bi-racial, middle-aged community-based sample participating in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort
Higher NT-proBNP concentrations were associated with smaller total GM volume (β = −3.44; 95% CI = −5.68, −1.20), but not with total WM volume (β = 0.45; 95% CI = −2.13, 3.029) after adjusting for potential confounders in both Model 1 and the fully adjusted Model 2 (Table 2)

Summary

Introduction

Several studies suggest a role for cardiac health in processes relating to brain atrophy and cognitive impairment at older age, leading to hypotheses concerning the heart–brain axis [1,2,3,4]. These hypotheses propose pathways through which cardiac dysfunction affects neurocognitive health, including perturbations in factors regulating cerebral perfusion resulting from blood barrier disruption, altered cardiac output, or atherosclerotic changes, that may, over time, lead to brain atrophy and cognitive impairment [5]. There is a clear association between heart failure and impaired cognition [7]; NT-proBNP level is a subclinical measure of cardiovascular dysfunction and a prognostic indicator of cerebrovascular morbidity and mortality [8, 9]

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