Timothy M Hughes1, Lynne E Wagenknecht2, Suzanne Craft2, Akiva Mintz2, Gerardo Heiss2, Priya Palta2, Dean Wong2, Yun Zhou2, David Knopman2, Thomas H Mosley2, Rebecca F Gottesman2. 1. From the Departments of Internal Medicine (T.M.H., S.C.) and Radiology (A.M.), and Division of Public Health Sciences (L.E.W.), Wake Forest School of Medicine, Winston-Salem, NC; Department of Epidemiology (G.H., P.P.), University of North Carolina at Chapel Hill; Departments of Radiology (D.W., Y.Z.) and Neurology (R.F.G.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (D.K.), Mayo Clinic, Rochester, MN; and Department of Medicine (T.H.M.), University of Mississippi Medical Center, Jackson. tmhughes@wakehealth.edu. 2. From the Departments of Internal Medicine (T.M.H., S.C.) and Radiology (A.M.), and Division of Public Health Sciences (L.E.W.), Wake Forest School of Medicine, Winston-Salem, NC; Department of Epidemiology (G.H., P.P.), University of North Carolina at Chapel Hill; Departments of Radiology (D.W., Y.Z.) and Neurology (R.F.G.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (D.K.), Mayo Clinic, Rochester, MN; and Department of Medicine (T.H.M.), University of Mississippi Medical Center, Jackson.
Abstract
OBJECTIVE: Arterial stiffness has been associated with evidence of cerebral small vessel disease (cSVD) and fibrillar β-amyloid (Aβ) deposition in the brain. These complex relationships have not been examined in racially and cognitively diverse cohorts. METHODS: The Atherosclerosis Risk in Communities (ARIC)-Neurocognitive Study collected detailed cognitive testing for adjudication of dementia and mild cognitive impairment (MCI), brain MRI, and arterial stiffness by pulse wave velocity (PWV, carotid-femoral [cfPWV] and heart-carotid [hcPWV]). The ARIC-PET ancillary study added Aβ imaging using florbetapir ([18F]-AV-45) to obtain standardized uptake volume ratios and defined global Aβ-positivity as standardized uptake volume ratio >1.2. One-SD increase in PWV was related to brain volume, MRI-defined cSVD (e.g., cerebral microbleeds and white matter hyperintensity), and cortical Aβ deposition adjusted for age, body mass index, sex, race, and APOE ε4 status. We examined the cross-sectional relationships including interactions by race, APOE ε4 status, and cognition. RESULTS: Among the 320 ARIC-PET participants (76 [5] years, 45% black, 27% MCI), greater central stiffness (hcPWV) was associated with greater Aβ deposition (odds ratio [OR] = 1.31, 95% confidence interval [CI] 1.01-1.71). Greater central stiffness (cfPWV) was significantly associated with having lower brain volumes in Alzheimer disease-susceptible regions (in mm3, β = -1.5 [0.7 SD], p = 0.03) and high white matter hyperintensity burden (OR = 1.6, 95% CI 1.2-2.1). Furthermore, cfPWV was associated with a higher odds of concomitant high white matter hyperintensity and Aβ-positive scans (OR = 1.4, 95% CI 1.1-2.1). These associations were strongest among individuals with MCI and did not differ by race or APOE ε4 status. CONCLUSIONS: Arterial stiffness, measured by PWV, is an emerging risk factor for dementia through its repeated relationships with cognition, cSVD, and Aβ deposition.
OBJECTIVE: Arterial stiffness has been associated with evidence of cerebral small vessel disease (cSVD) and fibrillar β-amyloid (Aβ) deposition in the brain. These complex relationships have not been examined in racially and cognitively diverse cohorts. METHODS: The Atherosclerosis Risk in Communities (ARIC)-Neurocognitive Study collected detailed cognitive testing for adjudication of dementia and mild cognitive impairment (MCI), brain MRI, and arterial stiffness by pulse wave velocity (PWV, carotid-femoral [cfPWV] and heart-carotid [hcPWV]). The ARIC-PET ancillary study added Aβ imaging using florbetapir ([18F]-AV-45) to obtain standardized uptake volume ratios and defined global Aβ-positivity as standardized uptake volume ratio >1.2. One-SD increase in PWV was related to brain volume, MRI-defined cSVD (e.g., cerebral microbleeds and white matter hyperintensity), and cortical Aβ deposition adjusted for age, body mass index, sex, race, and APOE ε4 status. We examined the cross-sectional relationships including interactions by race, APOE ε4 status, and cognition. RESULTS: Among the 320 ARIC-PET participants (76 [5] years, 45% black, 27% MCI), greater central stiffness (hcPWV) was associated with greater Aβ deposition (odds ratio [OR] = 1.31, 95% confidence interval [CI] 1.01-1.71). Greater central stiffness (cfPWV) was significantly associated with having lower brain volumes in Alzheimer disease-susceptible regions (in mm3, β = -1.5 [0.7 SD], p = 0.03) and high white matter hyperintensity burden (OR = 1.6, 95% CI 1.2-2.1). Furthermore, cfPWV was associated with a higher odds of concomitant high white matter hyperintensity and Aβ-positive scans (OR = 1.4, 95% CI 1.1-2.1). These associations were strongest among individuals with MCI and did not differ by race or APOE ε4 status. CONCLUSIONS: Arterial stiffness, measured by PWV, is an emerging risk factor for dementia through its repeated relationships with cognition, cSVD, and Aβ deposition.
Authors: Majd AlGhatrif; James B Strait; Chris H Morrell; Marco Canepa; Jeanette Wright; Palchamy Elango; Angelo Scuteri; Samer S Najjar; Luigi Ferrucci; Edward G Lakatta Journal: Hypertension Date: 2013-09-03 Impact factor: 10.190
Authors: Léon H G Henskens; Abraham A Kroon; Robert J van Oostenbrugge; Ed H B M Gronenschild; Monique M J J Fuss-Lejeune; Paul A M Hofman; Jan Lodder; Peter W de Leeuw Journal: Hypertension Date: 2008-10-13 Impact factor: 10.190
Authors: Leroy L Cooper; Todd Woodard; Sigurdur Sigurdsson; Mark A van Buchem; Alyssa A Torjesen; Lesley A Inker; Thor Aspelund; Gudny Eiriksdottir; Tamara B Harris; Vilmundur Gudnason; Lenore J Launer; Gary F Mitchell Journal: Hypertension Date: 2015-11-16 Impact factor: 10.190
Authors: Thomas J Montine; Walter J Koroshetz; Debra Babcock; Dennis W Dickson; Wendy R Galpern; M Maria Glymour; Steven M Greenberg; Michael L Hutton; David S Knopman; Andrey N Kuzmichev; Jennifer J Manly; Karen S Marder; Bruce L Miller; Creighton H Phelps; William W Seeley; Beth-Anne Sieber; Nina B Silverberg; Margaret Sutherland; Christine L Torborg; Salina P Waddy; Berislav V Zlokovic; Roderick A Corriveau Journal: Neurology Date: 2014-07-30 Impact factor: 9.910
Authors: Timothy M Hughes; Lewis H Kuller; Emma J M Barinas-Mitchell; Rachel H Mackey; Eric M McDade; William E Klunk; Howard J Aizenstein; Ann D Cohen; Beth E Snitz; Chester A Mathis; Steven T Dekosky; Oscar L Lopez Journal: Neurology Date: 2013-10-16 Impact factor: 9.910
Authors: C R Jack; P C O'Brien; D W Rettman; M M Shiung; Y Xu; R Muthupillai; A Manduca; R Avula; B J Erickson Journal: J Magn Reson Imaging Date: 2001-12 Impact factor: 4.813
Authors: Alastair J S Webb; Michela Simoni; Sara Mazzucco; Wilhelm Kuker; Ursula Schulz; Peter M Rothwell Journal: Stroke Date: 2012-08-23 Impact factor: 7.914
Authors: Sumudu V S Gangoda; Bhargava Avadhanam; Nurul F Jufri; Eun Hwa Sohn; Mark Butlin; Vivek Gupta; Roger Chung; Alberto P Avolio Journal: Sci Rep Date: 2018-01-26 Impact factor: 4.379
Authors: Carey E Gleason; Derek Norton; Megan Zuelsdorff; Susan F Benton; Mary F Wyman; Naomi Nystrom; Nickolas Lambrou; Hector Salazar; Rebecca L Koscik; Erin Jonaitis; Fabu Carter; Brieanna Harris; Alexander Gee; Nathaniel Chin; Frederick Ketchum; Sterling C Johnson; Dorothy F Edwards; Cynthia M Carlsson; Walter Kukull; Sanjay Asthana Journal: Alzheimers Dement Date: 2019-10-07 Impact factor: 21.566
Authors: Lindsay R Clark; Megan Zuelsdorff; Derek Norton; Sterling C Johnson; Mary F Wyman; Laura M Hancock; Cynthia M Carlsson; Sanjay Asthana; Susan Flowers-Benton; Carey E Gleason; Heather M Johnson Journal: J Alzheimers Dis Date: 2020 Impact factor: 4.472
Authors: Juan Carlos Yugar-Toledo; Heitor Moreno Júnior; Miguel Gus; Guido Bernardo Aranha Rosito; Luiz César Nazário Scala; Elizabeth Silaid Muxfeldt; Alexandre Alessi; Andrea Araújo Brandão; Osni Moreira Filho; Audes Diógenes de Magalhães Feitosa; Oswaldo Passarelli Júnior; Dilma do Socorro Moraes de Souza; Celso Amodeo; Weimar Kunz Sebba Barroso; Marco Antônio Mota Gomes; Annelise Machado Gomes de Paiva; Eduardo Costa Duarte Barbosa; Roberto Dischinger Miranda; José Fernando Vilela-Martin; Wilson Nadruz Júnior; Cibele Isaac Saad Rodrigues; Luciano Ferreira Drager; Luiz Aparecido Bortolotto; Fernanda Marciano Consolim-Colombo; Márcio Gonçalves de Sousa; Flávio Antonio de Oliveira Borelli; Sérgio Emanuel Kaiser; Gil Fernando Salles; Maria de Fátima de Azevedo; Lucélia Batista Neves Cunha Magalhães; Rui Manoel Dos Santos Póvoa; Marcus Vinícius Bolívar Malachias; Armando da Rocha Nogueira; Paulo César Brandão Veiga Jardim; Thiago de Souza Veiga Jardim Journal: Arq Bras Cardiol Date: 2020 May-Jun Impact factor: 2.000
Authors: Lindsay R Clark; Derek Norton; Sara E Berman; Sterling C Johnson; Barbara B Bendlin; Oliver Wieben; Patrick Turski; Cynthia Carlsson; Sanjay Asthana; Carey E Gleason; Heather M Johnson Journal: J Alzheimers Dis Date: 2019 Impact factor: 4.472
Authors: Leonardo A Rivera-Rivera; Karly A Cody; Laura Eisenmenger; Paul Cary; Howard A Rowley; Cynthia M Carlsson; Sterling C Johnson; Kevin M Johnson Journal: J Cereb Blood Flow Metab Date: 2020-03-13 Impact factor: 6.200