Behnam Sabayan1, Mark A van Buchem1, Anton J M de Craen1, Sigurdur Sigurdsson1, Qian Zhang1, Tamara B Harris1, Vilmundur Gudnason1, Andrew E Arai1, Lenore J Launer2. 1. 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. 2. 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.
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.
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: Raymond L C Vogels; Wiesje M van der Flier; Barbera van Harten; Alida A Gouw; Philip Scheltens; Jutta M Schroeder-Tanka; Henry C Weinstein Journal: Eur J Heart Fail Date: 2007-08-23 Impact factor: 15.534
Authors: Kristen K Patton; Patrick T Ellinor; Susan R Heckbert; Robert H Christenson; Christopher DeFilippi; John S Gottdiener; Richard A Kronmal Journal: Circulation Date: 2009-10-19 Impact factor: 29.690
Authors: Matti Hiltunen; Tuomo Nieminen; Raimo Kettunen; Sirpa Hartikainen; Raimo Sulkava; Olli Vuolteenaho; Tuomas Kerola Journal: Eur J Clin Invest Date: 2013-09-17 Impact factor: 4.686
Authors: Razvan T Dadu; Myriam Fornage; Salim S Virani; Vijay Nambi; Ron C Hoogeveen; Eric Boerwinkle; Alvaro Alonso; Rebecca F Gottesman; Thomas H Mosley; Christie M Ballantyne Journal: Stroke Date: 2013-05-09 Impact factor: 7.914
Authors: Erik B Schelbert; Jie J Cao; Sigurdur Sigurdsson; Thor Aspelund; Peter Kellman; Anthony H Aletras; Christopher K Dyke; Gudmundur Thorgeirsson; Gudny Eiriksdottir; Lenore J Launer; Vilmundur Gudnason; Tamara B Harris; Andrew E Arai Journal: JAMA Date: 2012-09-05 Impact factor: 56.272
Authors: Lewis H Kuller; Oscar L Lopez; John S Gottdiener; Dalane W Kitzman; James T Becker; Yuefang Chang; Anne B Newman Journal: J Am Heart Assoc Date: 2017-07-22 Impact factor: 5.501
Authors: Simin Mahinrad; Marjolein Bulk; Isabelle van der Velpen; Ahmed Mahfouz; Willeke van Roon-Mom; Neal Fedarko; Sevil Yasar; Behnam Sabayan; Diana van Heemst; Louise van der Weerd Journal: Front Neurosci Date: 2018-11-26 Impact factor: 4.677
Authors: Ian T Ferguson; Martine Elbejjani; Behnam Sabayan; David R Jacobs; Osorio Meirelles; Otto A Sanchez; Russell Tracy; Nick Bryan; Lenore J Launer Journal: Front Neurol Date: 2018-05-07 Impact factor: 4.003