title: N-terminal pro-brain natriuretic peptide and abnormal brain aging: The AGES-Reykjavik Study.
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 = 0.001) brain volumes. Likewise, in multivariate analyses, higher levels of NT-proBNP were associated with worse scores in memory (p = 0.005), processing speed (p = 0.001), executive functioning (p < 0.001), and more depressive symptoms (p = 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.
authors.affiliation: From the Departments of Radiology (B.S., M.A.v.B.) and Gerontology and Geriatrics (B.S., A.J.M.d.C.), Leiden University Medical Center, the Netherlands; Icelandic Heart Association (S.S., V.G.), Reykjavik, Iceland; Intramural Research Program (Q.Z., T.B.H., L.J.L.), National Institute on Aging, NIH, Bethesda, MD; Faculty of Medicine (V.G.), University of Iceland, Reykjavik; and Cardiovascular and Pulmonary Branch (A.E.A.), National Heart, Lung, and Blood Institute, NIH, Bethesda, MD.
authors.forename: Behnam
authors.initials: B
authors.lastname: Sabayan
authors.affiliation: From the Departments of Radiology (B.S., M.A.v.B.) and Gerontology and Geriatrics (B.S., A.J.M.d.C.), Leiden University Medical Center, the Netherlands; Icelandic Heart Association (S.S., V.G.), Reykjavik, Iceland; Intramural Research Program (Q.Z., T.B.H., L.J.L.), National Institute on Aging, NIH, Bethesda, MD; Faculty of Medicine (V.G.), University of Iceland, Reykjavik; and Cardiovascular and Pulmonary Branch (A.E.A.), National Heart, Lung, and Blood Institute, NIH, Bethesda, MD.
authors.forename: Mark A
authors.initials: MA
authors.lastname: van Buchem
authors.affiliation: From the Departments of Radiology (B.S., M.A.v.B.) and Gerontology and Geriatrics (B.S., A.J.M.d.C.), Leiden University Medical Center, the Netherlands; Icelandic Heart Association (S.S., V.G.), Reykjavik, Iceland; Intramural Research Program (Q.Z., T.B.H., L.J.L.), National Institute on Aging, NIH, Bethesda, MD; Faculty of Medicine (V.G.), University of Iceland, Reykjavik; and Cardiovascular and Pulmonary Branch (A.E.A.), National Heart, Lung, and Blood Institute, NIH, Bethesda, MD.
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: de Craen
authors.affiliation: From the Departments of Radiology (B.S., M.A.v.B.) and Gerontology and Geriatrics (B.S., A.J.M.d.C.), Leiden University Medical Center, the Netherlands; Icelandic Heart Association (S.S., V.G.), Reykjavik, Iceland; Intramural Research Program (Q.Z., T.B.H., L.J.L.), National Institute on Aging, NIH, Bethesda, MD; Faculty of Medicine (V.G.), University of Iceland, Reykjavik; and Cardiovascular and Pulmonary Branch (A.E.A.), National Heart, Lung, and Blood Institute, NIH, Bethesda, MD.
authors.forename: Sigurdur
authors.initials: S
authors.lastname: Sigurdsson
authors.affiliation: From the Departments of Radiology (B.S., M.A.v.B.) and Gerontology and Geriatrics (B.S., A.J.M.d.C.), Leiden University Medical Center, the Netherlands; Icelandic Heart Association (S.S., V.G.), Reykjavik, Iceland; Intramural Research Program (Q.Z., T.B.H., L.J.L.), National Institute on Aging, NIH, Bethesda, MD; Faculty of Medicine (V.G.), University of Iceland, Reykjavik; and Cardiovascular and Pulmonary Branch (A.E.A.), National Heart, Lung, and Blood Institute, NIH, Bethesda, MD.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: From the Departments of Radiology (B.S., M.A.v.B.) and Gerontology and Geriatrics (B.S., A.J.M.d.C.), Leiden University Medical Center, the Netherlands; Icelandic Heart Association (S.S., V.G.), Reykjavik, Iceland; Intramural Research Program (Q.Z., T.B.H., L.J.L.), National Institute on Aging, NIH, Bethesda, MD; Faculty of Medicine (V.G.), University of Iceland, Reykjavik; and Cardiovascular and Pulmonary Branch (A.E.A.), National Heart, Lung, and Blood Institute, NIH, Bethesda, MD.
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
authors.affiliation: From the Departments of Radiology (B.S., M.A.v.B.) and Gerontology and Geriatrics (B.S., A.J.M.d.C.), Leiden University Medical Center, the Netherlands; Icelandic Heart Association (S.S., V.G.), Reykjavik, Iceland; Intramural Research Program (Q.Z., T.B.H., L.J.L.), National Institute on Aging, NIH, Bethesda, MD; Faculty of Medicine (V.G.), University of Iceland, Reykjavik; and Cardiovascular and Pulmonary Branch (A.E.A.), National Heart, Lung, and Blood Institute, NIH, Bethesda, MD.
authors.forename: Vilmundur
authors.initials: V
authors.lastname: Gudnason
authors.affiliation: From the Departments of Radiology (B.S., M.A.v.B.) and Gerontology and Geriatrics (B.S., A.J.M.d.C.), Leiden University Medical Center, the Netherlands; Icelandic Heart Association (S.S., V.G.), Reykjavik, Iceland; Intramural Research Program (Q.Z., T.B.H., L.J.L.), National Institute on Aging, NIH, Bethesda, MD; Faculty of Medicine (V.G.), University of Iceland, Reykjavik; and Cardiovascular and Pulmonary Branch (A.E.A.), National Heart, Lung, and Blood Institute, NIH, Bethesda, MD.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Arai
authors.affiliation: From the Departments of Radiology (B.S., M.A.v.B.) and Gerontology and Geriatrics (B.S., A.J.M.d.C.), Leiden University Medical Center, the Netherlands; Icelandic Heart Association (S.S., V.G.), Reykjavik, Iceland; Intramural Research Program (Q.Z., T.B.H., L.J.L.), National Institute on Aging, NIH, Bethesda, MD; Faculty of Medicine (V.G.), University of Iceland, Reykjavik; and Cardiovascular and Pulmonary Branch (A.E.A.), National Heart, Lung, and Blood Institute, NIH, Bethesda, MD. launerl@nia.nih.gov.
authors.forename: Lenore J
authors.initials: LJ
authors.lastname: Launer
mesh_terms: D000368:Aged; D000375:Aging / Q000097:blood* / Q000473:pathology* / Q000523:psychology; D001921:Brain / Q000473:pathology*; D002318:Cardiovascular Diseases / Q000503:physiopathology; D003071:Cognition; D003430:Cross-Sectional Studies; D003863:Depression; D005260:Female; D066128:Gray Matter / Q000473:pathology; D006334:Heart Function Tests; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D015999:Multivariate Analysis; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D009483:Neuropsychological Tests; D009929:Organ Size; D010446:Peptide Fragments / Q000097:blood*; D012307:Risk Factors; D066127:White Matter / Q000473:pathology
chemical_list: D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain