title: Cerebrovascular Damage Mediates Relations Between Aortic Stiffness and Memory.
abstract: Aortic stiffness is associated with cognitive decline. Here, we examined the association between carotid-femoral pulse wave velocity and cognitive function and investigated whether cerebrovascular remodeling and parenchymal small vessel disease damage mediate the relation. Analyses were based on 1820 (60% women) participants in the Age, Gene/Environment Susceptibility-Reykjavik Study. Multivariable linear regression models adjusted for vascular and demographic confounders showed that higher carotid-femoral pulse wave velocity was related to lower memory score (standardized β: -0.071±0.023; P=0.002). Cerebrovascular resistance and white matter hyperintensities were each associated with carotid-femoral pulse wave velocity and memory (P<0.05). Together, cerebrovascular resistance and white matter hyperintensities (total indirect effect: -0.029; 95% CI, -0.043 to -0.017) attenuated the direct relation between carotid-femoral pulse wave velocity and memory (direct effect: -0.042; 95% CI, -0.087 to 0.003; P=0.07) and explained ≈41% of the observed effect. Our results suggest that in older adults, associations between aortic stiffness and memory are mediated by pathways that include cerebral microvascular remodeling and microvascular parenchymal damage.
authors.affiliation: From the Cardiovascular Engineering, Inc, Norwood, MA (L.L.C., T.W., A.A.T., G.F.M.); Cardiovascular Research Center, Rhode Island Hospital, W. Alpert Medical School of Brown University, Providence, RI (L.L.C.); Icelandic Heart Association, Kopavogur, Iceland (S.S., T.A., G.E., V.G.); Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands (M.A.B.); Division of Nephrology and Department of Medicine, Tufts Medical Center, Boston, MA (L.A.I.); Faculty of Medicine, University of Iceland, Reykjavik, Iceland (T.A., V.G.); and Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, MD (T.B.H., L.J.L.).
authors.forename: Leroy L
authors.initials: LL
authors.lastname: Cooper
authors.affiliation: From the Cardiovascular Engineering, Inc, Norwood, MA (L.L.C., T.W., A.A.T., G.F.M.); Cardiovascular Research Center, Rhode Island Hospital, W. Alpert Medical School of Brown University, Providence, RI (L.L.C.); Icelandic Heart Association, Kopavogur, Iceland (S.S., T.A., G.E., V.G.); Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands (M.A.B.); Division of Nephrology and Department of Medicine, Tufts Medical Center, Boston, MA (L.A.I.); Faculty of Medicine, University of Iceland, Reykjavik, Iceland (T.A., V.G.); and Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, MD (T.B.H., L.J.L.).
authors.forename: Todd
authors.initials: T
authors.lastname: Woodard
authors.affiliation: From the Cardiovascular Engineering, Inc, Norwood, MA (L.L.C., T.W., A.A.T., G.F.M.); Cardiovascular Research Center, Rhode Island Hospital, W. Alpert Medical School of Brown University, Providence, RI (L.L.C.); Icelandic Heart Association, Kopavogur, Iceland (S.S., T.A., G.E., V.G.); Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands (M.A.B.); Division of Nephrology and Department of Medicine, Tufts Medical Center, Boston, MA (L.A.I.); Faculty of Medicine, University of Iceland, Reykjavik, Iceland (T.A., V.G.); and Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, MD (T.B.H., L.J.L.).
authors.forename: Sigurdur
authors.initials: S
authors.lastname: Sigurdsson
authors.affiliation: From the Cardiovascular Engineering, Inc, Norwood, MA (L.L.C., T.W., A.A.T., G.F.M.); Cardiovascular Research Center, Rhode Island Hospital, W. Alpert Medical School of Brown University, Providence, RI (L.L.C.); Icelandic Heart Association, Kopavogur, Iceland (S.S., T.A., G.E., V.G.); Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands (M.A.B.); Division of Nephrology and Department of Medicine, Tufts Medical Center, Boston, MA (L.A.I.); Faculty of Medicine, University of Iceland, Reykjavik, Iceland (T.A., V.G.); and Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, MD (T.B.H., L.J.L.).
authors.forename: Mark A
authors.initials: MA
authors.lastname: van Buchem
authors.affiliation: From the Cardiovascular Engineering, Inc, Norwood, MA (L.L.C., T.W., A.A.T., G.F.M.); Cardiovascular Research Center, Rhode Island Hospital, W. Alpert Medical School of Brown University, Providence, RI (L.L.C.); Icelandic Heart Association, Kopavogur, Iceland (S.S., T.A., G.E., V.G.); Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands (M.A.B.); Division of Nephrology and Department of Medicine, Tufts Medical Center, Boston, MA (L.A.I.); Faculty of Medicine, University of Iceland, Reykjavik, Iceland (T.A., V.G.); and Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, MD (T.B.H., L.J.L.).
authors.forename: Alyssa A
authors.initials: AA
authors.lastname: Torjesen
authors.affiliation: From the Cardiovascular Engineering, Inc, Norwood, MA (L.L.C., T.W., A.A.T., G.F.M.); Cardiovascular Research Center, Rhode Island Hospital, W. Alpert Medical School of Brown University, Providence, RI (L.L.C.); Icelandic Heart Association, Kopavogur, Iceland (S.S., T.A., G.E., V.G.); Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands (M.A.B.); Division of Nephrology and Department of Medicine, Tufts Medical Center, Boston, MA (L.A.I.); Faculty of Medicine, University of Iceland, Reykjavik, Iceland (T.A., V.G.); and Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, MD (T.B.H., L.J.L.).
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Inker
authors.affiliation: From the Cardiovascular Engineering, Inc, Norwood, MA (L.L.C., T.W., A.A.T., G.F.M.); Cardiovascular Research Center, Rhode Island Hospital, W. Alpert Medical School of Brown University, Providence, RI (L.L.C.); Icelandic Heart Association, Kopavogur, Iceland (S.S., T.A., G.E., V.G.); Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands (M.A.B.); Division of Nephrology and Department of Medicine, Tufts Medical Center, Boston, MA (L.A.I.); Faculty of Medicine, University of Iceland, Reykjavik, Iceland (T.A., V.G.); and Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, MD (T.B.H., L.J.L.).
authors.forename: Thor
authors.initials: T
authors.lastname: Aspelund
authors.affiliation: From the Cardiovascular Engineering, Inc, Norwood, MA (L.L.C., T.W., A.A.T., G.F.M.); Cardiovascular Research Center, Rhode Island Hospital, W. Alpert Medical School of Brown University, Providence, RI (L.L.C.); Icelandic Heart Association, Kopavogur, Iceland (S.S., T.A., G.E., V.G.); Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands (M.A.B.); Division of Nephrology and Department of Medicine, Tufts Medical Center, Boston, MA (L.A.I.); Faculty of Medicine, University of Iceland, Reykjavik, Iceland (T.A., V.G.); and Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, MD (T.B.H., L.J.L.).
authors.forename: Gudny
authors.initials: G
authors.lastname: Eiriksdottir
authors.affiliation: From the Cardiovascular Engineering, Inc, Norwood, MA (L.L.C., T.W., A.A.T., G.F.M.); Cardiovascular Research Center, Rhode Island Hospital, W. Alpert Medical School of Brown University, Providence, RI (L.L.C.); Icelandic Heart Association, Kopavogur, Iceland (S.S., T.A., G.E., V.G.); Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands (M.A.B.); Division of Nephrology and Department of Medicine, Tufts Medical Center, Boston, MA (L.A.I.); Faculty of Medicine, University of Iceland, Reykjavik, Iceland (T.A., V.G.); and Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, MD (T.B.H., L.J.L.).
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
authors.affiliation: From the Cardiovascular Engineering, Inc, Norwood, MA (L.L.C., T.W., A.A.T., G.F.M.); Cardiovascular Research Center, Rhode Island Hospital, W. Alpert Medical School of Brown University, Providence, RI (L.L.C.); Icelandic Heart Association, Kopavogur, Iceland (S.S., T.A., G.E., V.G.); Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands (M.A.B.); Division of Nephrology and Department of Medicine, Tufts Medical Center, Boston, MA (L.A.I.); Faculty of Medicine, University of Iceland, Reykjavik, Iceland (T.A., V.G.); and Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, MD (T.B.H., L.J.L.).
authors.forename: Vilmundur
authors.initials: V
authors.lastname: Gudnason
authors.affiliation: From the Cardiovascular Engineering, Inc, Norwood, MA (L.L.C., T.W., A.A.T., G.F.M.); Cardiovascular Research Center, Rhode Island Hospital, W. Alpert Medical School of Brown University, Providence, RI (L.L.C.); Icelandic Heart Association, Kopavogur, Iceland (S.S., T.A., G.E., V.G.); Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands (M.A.B.); Division of Nephrology and Department of Medicine, Tufts Medical Center, Boston, MA (L.A.I.); Faculty of Medicine, University of Iceland, Reykjavik, Iceland (T.A., V.G.); and Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, MD (T.B.H., L.J.L.).
authors.forename: Lenore J
authors.initials: LJ
authors.lastname: Launer
authors.affiliation: From the Cardiovascular Engineering, Inc, Norwood, MA (L.L.C., T.W., A.A.T., G.F.M.); Cardiovascular Research Center, Rhode Island Hospital, W. Alpert Medical School of Brown University, Providence, RI (L.L.C.); Icelandic Heart Association, Kopavogur, Iceland (S.S., T.A., G.E., V.G.); Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands (M.A.B.); Division of Nephrology and Department of Medicine, Tufts Medical Center, Boston, MA (L.A.I.); Faculty of Medicine, University of Iceland, Reykjavik, Iceland (T.A., V.G.); and Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, MD (T.B.H., L.J.L.). GaryFMitchell@mindspring.com.
authors.forename: Gary F
authors.initials: GF
authors.lastname: Mitchell
mesh_terms: D000369:Aged, 80 and over; D001013:Aorta, Thoracic / Q000503:physiopathology*; D001794:Blood Pressure; D001921:Brain / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D002561:Cerebrovascular Disorders / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology*; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology*; D011673:Pulsatile Flow; D063177:Pulse Wave Analysis; D059289:Vascular Stiffness / Q000502:physiology*
keywords: cognition; dementia; hemodynamics; memory; vascular stiffness