title: Association of arterial stiffness with progression of subclinical brain and cognitive disease.
abstract: OBJECTIVE
  We tested whether abnormal arterial stiffness and blood pressure would be associated with progression of brain aging measured by brain MRI and neurocognitive testing.
  
  
  METHODS
  Framingham Offspring Cohort participants (n = 1,223, 61 ± 9 years, 56% women) without previous stroke or dementia underwent applanation tonometry, brain MRI, and neurocognitive testing at examination 7 (1998-2001). Follow-up brain MRI and neurocognitive testing was performed at examination 8 (2005-2008, mean interval 6.4 ± 1.3 years). We related examination 7 inverse-transformed carotid-femoral pulse wave velocity (iCFPWV), central pulse pressure (CPP), and mean arterial pressure to changes in the following variables between examinations 7 and 8: total cerebral brain volume, white matter hyperintensity volume, and performance on executive function and abstraction tasks, the Trail Making Test, Parts B and A (ΔTrails B-A), and Similarities tests.
  
  
  RESULTS
  Higher baseline iCFPWV and CPP were associated with greater progression of neurocognitive decline (iCFPWV and ΔTrails B-A association: SD unit change in outcome variable per SD change in tonometry variable [β] ± SE = 0.10 ± 0.04, p = 0.019; CPP and ΔSimilarities association: -0.08 ± 0.03, p = 0.013). Higher mean arterial pressure, but not iCFPWV or CPP, was associated with increase in white matter hyperintensity volume ([β ± SE] 0.07 ± 0.03, p = 0.017). No tonometry measures were associated with change in cerebral brain volume.
  
  
  CONCLUSIONS
  In middle-aged and older adults without evidence of clinical stroke or dementia, elevated arterial stiffness and pressure pulsatility are associated with longitudinal progression of subclinical vascular brain injury and greater neurocognitive decline. Treatments to reduce arterial stiffness may potentially reduce the progression of neurovascular disease and cognitive decline.
authors.affiliation: From the Department of Medicine (C.W.T.), Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, MA; Departments of Neurology (J.J.H., A.S.B., S.S.) and Medicine (R.S.V.), School of Medicine, Departments of Biostatistics (J.J.H., A.S.B.) and Epidemiology (R.S.V.), School of Public Health, and the Department of Mathematics and Statistics (M.G.L.), Boston University, Boston, MA; Department of Neurology and Center for Neuroscience and Division of Biostatistics (C.D.), Department of Public Health Sciences, School of Medicine, University of California, Davis, CA; The Framingham Heart Study (C.W.T., J.J.H., A.S.B., M.G.L., R.S.V., S.S.), Framingham, MA; and Cardiovascular Engineering Inc. (G.F.M.), Norwood, MA. ctsao1@bidmc.harvard.edu.
authors.forename: Connie W
authors.initials: CW
authors.lastname: Tsao
authors.affiliation: From the Department of Medicine (C.W.T.), Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, MA; Departments of Neurology (J.J.H., A.S.B., S.S.) and Medicine (R.S.V.), School of Medicine, Departments of Biostatistics (J.J.H., A.S.B.) and Epidemiology (R.S.V.), School of Public Health, and the Department of Mathematics and Statistics (M.G.L.), Boston University, Boston, MA; Department of Neurology and Center for Neuroscience and Division of Biostatistics (C.D.), Department of Public Health Sciences, School of Medicine, University of California, Davis, CA; The Framingham Heart Study (C.W.T., J.J.H., A.S.B., M.G.L., R.S.V., S.S.), Framingham, MA; and Cardiovascular Engineering Inc. (G.F.M.), Norwood, MA.
authors.forename: Jayandra J
authors.initials: JJ
authors.lastname: Himali
authors.affiliation: From the Department of Medicine (C.W.T.), Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, MA; Departments of Neurology (J.J.H., A.S.B., S.S.) and Medicine (R.S.V.), School of Medicine, Departments of Biostatistics (J.J.H., A.S.B.) and Epidemiology (R.S.V.), School of Public Health, and the Department of Mathematics and Statistics (M.G.L.), Boston University, Boston, MA; Department of Neurology and Center for Neuroscience and Division of Biostatistics (C.D.), Department of Public Health Sciences, School of Medicine, University of California, Davis, CA; The Framingham Heart Study (C.W.T., J.J.H., A.S.B., M.G.L., R.S.V., S.S.), Framingham, MA; and Cardiovascular Engineering Inc. (G.F.M.), Norwood, MA.
authors.forename: Alexa S
authors.initials: AS
authors.lastname: Beiser
authors.affiliation: From the Department of Medicine (C.W.T.), Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, MA; Departments of Neurology (J.J.H., A.S.B., S.S.) and Medicine (R.S.V.), School of Medicine, Departments of Biostatistics (J.J.H., A.S.B.) and Epidemiology (R.S.V.), School of Public Health, and the Department of Mathematics and Statistics (M.G.L.), Boston University, Boston, MA; Department of Neurology and Center for Neuroscience and Division of Biostatistics (C.D.), Department of Public Health Sciences, School of Medicine, University of California, Davis, CA; The Framingham Heart Study (C.W.T., J.J.H., A.S.B., M.G.L., R.S.V., S.S.), Framingham, MA; and Cardiovascular Engineering Inc. (G.F.M.), Norwood, MA.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.affiliation: From the Department of Medicine (C.W.T.), Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, MA; Departments of Neurology (J.J.H., A.S.B., S.S.) and Medicine (R.S.V.), School of Medicine, Departments of Biostatistics (J.J.H., A.S.B.) and Epidemiology (R.S.V.), School of Public Health, and the Department of Mathematics and Statistics (M.G.L.), Boston University, Boston, MA; Department of Neurology and Center for Neuroscience and Division of Biostatistics (C.D.), Department of Public Health Sciences, School of Medicine, University of California, Davis, CA; The Framingham Heart Study (C.W.T., J.J.H., A.S.B., M.G.L., R.S.V., S.S.), Framingham, MA; and Cardiovascular Engineering Inc. (G.F.M.), Norwood, MA.
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
authors.affiliation: From the Department of Medicine (C.W.T.), Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, MA; Departments of Neurology (J.J.H., A.S.B., S.S.) and Medicine (R.S.V.), School of Medicine, Departments of Biostatistics (J.J.H., A.S.B.) and Epidemiology (R.S.V.), School of Public Health, and the Department of Mathematics and Statistics (M.G.L.), Boston University, Boston, MA; Department of Neurology and Center for Neuroscience and Division of Biostatistics (C.D.), Department of Public Health Sciences, School of Medicine, University of California, Davis, CA; The Framingham Heart Study (C.W.T., J.J.H., A.S.B., M.G.L., R.S.V., S.S.), Framingham, MA; and Cardiovascular Engineering Inc. (G.F.M.), Norwood, MA.
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.affiliation: From the Department of Medicine (C.W.T.), Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, MA; Departments of Neurology (J.J.H., A.S.B., S.S.) and Medicine (R.S.V.), School of Medicine, Departments of Biostatistics (J.J.H., A.S.B.) and Epidemiology (R.S.V.), School of Public Health, and the Department of Mathematics and Statistics (M.G.L.), Boston University, Boston, MA; Department of Neurology and Center for Neuroscience and Division of Biostatistics (C.D.), Department of Public Health Sciences, School of Medicine, University of California, Davis, CA; The Framingham Heart Study (C.W.T., J.J.H., A.S.B., M.G.L., R.S.V., S.S.), Framingham, MA; and Cardiovascular Engineering Inc. (G.F.M.), Norwood, MA.
authors.forename: Gary F
authors.initials: GF
authors.lastname: Mitchell
authors.affiliation: From the Department of Medicine (C.W.T.), Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, MA; Departments of Neurology (J.J.H., A.S.B., S.S.) and Medicine (R.S.V.), School of Medicine, Departments of Biostatistics (J.J.H., A.S.B.) and Epidemiology (R.S.V.), School of Public Health, and the Department of Mathematics and Statistics (M.G.L.), Boston University, Boston, MA; Department of Neurology and Center for Neuroscience and Division of Biostatistics (C.D.), Department of Public Health Sciences, School of Medicine, University of California, Davis, CA; The Framingham Heart Study (C.W.T., J.J.H., A.S.B., M.G.L., R.S.V., S.S.), Framingham, MA; and Cardiovascular Engineering Inc. (G.F.M.), Norwood, MA.
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
mesh_terms: D001794:Blood Pressure; D001921:Brain / Q000473:pathology; D001927:Brain Diseases / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology*; D003072:Cognition Disorders / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008365:Manometry; D008875:Middle Aged; D009483:Neuropsychological Tests; D009929:Organ Size; D059289:Vascular Stiffness; D066127:White Matter / Q000473:pathology