Cardiac and Carotid Markers Link With Accelerated Brain Atrophy: The AGES-Reykjavik Study (Age, Gene/Environment Susceptibility-Reykjavik).
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.



In the longitudinal population-based AGES-Reykjavik study (Age, Gene/Environment Susceptibility-Reykjavik), we included 2430 subjects (mean age, 74.6 years; 41.4% men) with baseline data on NT-proBNP and CITM (assessed by ultrasound imaging). Participants underwent a high-resolution brain magnetic resonance imaging at baseline and 5 years later to assess total brain (TBV), gray matter, and white matter volumes. Each unit higher log-transformed NT-proBNP was associated with 3.6 mL (95% confidence interval [CI], -6.0 to -1.1) decline in TBV and 3.5 mL (95% CI, -5.7 to -1.3) decline in gray matter volume. Likewise, each millimeter higher CIMT was associated with 10.8 mL (95% CI, -17.3 to -4.2) decline in TBV and 8.6 mL (95% CI, -14.4 to -2.8) decline in gray matter volume. There was no association between NT-proBNP and CIMT and changes in white matter volume. Compared with participants with low NT-proBNP and CIMT, participants with both high NT-proBNP and CIMT had 3.8 mL (95% CI, -6.0 to -1.6) greater decline in their TBV and 4 mL (95% CI, -6.0 to -2.0) greater decline in GMW. These associations were independent of sociodemographic and cardiovascular factors.



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.
From the Department of Radiology (B.S., M.A.v.B.), Department of Gerontology and Geriatrics (B.S.), Leiden University Medical Center, The Netherlands; Leiden Institute for Brain and Cognition, Leiden University, The Netherlands (M.A.v.B.); Icelandic Heart Association, Reykjavik (S.S., V.G.); Intramural Research Program, National Institute on Ageing (Q.Z., O.M., T.B.H., L.J.L.) and Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute (A.E.A.), National Institutes of Health, Bethesda, MD.
Behnam
B
Sabayan
From the Department of Radiology (B.S., M.A.v.B.), Department of Gerontology and Geriatrics (B.S.), Leiden University Medical Center, The Netherlands; Leiden Institute for Brain and Cognition, Leiden University, The Netherlands (M.A.v.B.); Icelandic Heart Association, Reykjavik (S.S., V.G.); Intramural Research Program, National Institute on Ageing (Q.Z., O.M., T.B.H., L.J.L.) and Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute (A.E.A.), National Institutes of Health, Bethesda, MD.
Mark A
MA
van Buchem
From the Department of Radiology (B.S., M.A.v.B.), Department of Gerontology and Geriatrics (B.S.), Leiden University Medical Center, The Netherlands; Leiden Institute for Brain and Cognition, Leiden University, The Netherlands (M.A.v.B.); Icelandic Heart Association, Reykjavik (S.S., V.G.); Intramural Research Program, National Institute on Ageing (Q.Z., O.M., T.B.H., L.J.L.) and Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute (A.E.A.), National Institutes of Health, Bethesda, MD.
Sigurdur
S
Sigurdsson
From the Department of Radiology (B.S., M.A.v.B.), Department of Gerontology and Geriatrics (B.S.), Leiden University Medical Center, The Netherlands; Leiden Institute for Brain and Cognition, Leiden University, The Netherlands (M.A.v.B.); Icelandic Heart Association, Reykjavik (S.S., V.G.); Intramural Research Program, National Institute on Ageing (Q.Z., O.M., T.B.H., L.J.L.) and Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute (A.E.A.), National Institutes of Health, Bethesda, MD.
Qian
Q
Zhang
From the Department of Radiology (B.S., M.A.v.B.), Department of Gerontology and Geriatrics (B.S.), Leiden University Medical Center, The Netherlands; Leiden Institute for Brain and Cognition, Leiden University, The Netherlands (M.A.v.B.); Icelandic Heart Association, Reykjavik (S.S., V.G.); Intramural Research Program, National Institute on Ageing (Q.Z., O.M., T.B.H., L.J.L.) and Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute (A.E.A.), National Institutes of Health, Bethesda, MD.
Osorio
O
Meirelles
From the Department of Radiology (B.S., M.A.v.B.), Department of Gerontology and Geriatrics (B.S.), Leiden University Medical Center, The Netherlands; Leiden Institute for Brain and Cognition, Leiden University, The Netherlands (M.A.v.B.); Icelandic Heart Association, Reykjavik (S.S., V.G.); Intramural Research Program, National Institute on Ageing (Q.Z., O.M., T.B.H., L.J.L.) and Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute (A.E.A.), National Institutes of Health, Bethesda, MD.
Tamara B
TB
Harris
From the Department of Radiology (B.S., M.A.v.B.), Department of Gerontology and Geriatrics (B.S.), Leiden University Medical Center, The Netherlands; Leiden Institute for Brain and Cognition, Leiden University, The Netherlands (M.A.v.B.); Icelandic Heart Association, Reykjavik (S.S., V.G.); Intramural Research Program, National Institute on Ageing (Q.Z., O.M., T.B.H., L.J.L.) and Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute (A.E.A.), National Institutes of Health, Bethesda, MD.
Vilmundur
V
Gudnason
From the Department of Radiology (B.S., M.A.v.B.), Department of Gerontology and Geriatrics (B.S.), Leiden University Medical Center, The Netherlands; Leiden Institute for Brain and Cognition, Leiden University, The Netherlands (M.A.v.B.); Icelandic Heart Association, Reykjavik (S.S., V.G.); Intramural Research Program, National Institute on Ageing (Q.Z., O.M., T.B.H., L.J.L.) and Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute (A.E.A.), National Institutes of Health, Bethesda, MD.
Andrew E
AE
Arai
From the Department of Radiology (B.S., M.A.v.B.), Department of Gerontology and Geriatrics (B.S.), Leiden University Medical Center, The Netherlands; Leiden Institute for Brain and Cognition, Leiden University, The Netherlands (M.A.v.B.); Icelandic Heart Association, Reykjavik (S.S., V.G.); Intramural Research Program, National Institute on Ageing (Q.Z., O.M., T.B.H., L.J.L.) and Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute (A.E.A.), National Institutes of Health, Bethesda, MD. launerl@nia.nih.gov.
Lenore J
LJ
Launer
D000367:Age Factors; D000368:Aged; D001284:Atrophy; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000000981:diagnostic imaging*; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000235:genetics; D059168:Carotid Intima-Media Thickness; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006331:Heart Diseases / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D007055:Iceland / Q000453:epidemiology; D056784:Leukoencephalopathies / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
brain; brain natriuretic peptide; carotid stenosis; gray matter; white matter