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February 16, 2016; 86 (7) Article

Association of arterial stiffness with progression of subclinical brain and cognitive disease

Connie W. Tsao, Jayandra J. Himali, Alexa S. Beiser, Martin G. Larson, Charles DeCarli, Ramachandran S. Vasan, Gary F. Mitchell, Sudha Seshadri
First published January 20, 2016, DOI: https://doi.org/10.1212/WNL.0000000000002368
Connie W. Tsao
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.
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Jayandra J. Himali
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.
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Alexa S. Beiser
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.
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Martin G. Larson
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.
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Charles DeCarli
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.
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Ramachandran S. Vasan
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.
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Gary F. Mitchell
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.
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Sudha Seshadri
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.
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Citation
Association of arterial stiffness with progression of subclinical brain and cognitive disease
Connie W. Tsao, Jayandra J. Himali, Alexa S. Beiser, Martin G. Larson, Charles DeCarli, Ramachandran S. Vasan, Gary F. Mitchell, Sudha Seshadri
Neurology Feb 2016, 86 (7) 619-626; DOI: 10.1212/WNL.0000000000002368

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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.

GLOSSARY

CI=
confidence interval;
CPP=
central pulse pressure;
CVD=
cardiovascular disease;
FHS=
Framingham Heart Study;
iCFPWV=
inverse-transformed carotid-femoral pulse wave velocity;
MAP=
mean arterial pressure;
PWV=
pulse wave velocity;
TCBV=
total cerebral brain volume;
Trails B-A=
Trail Making Test Part B minus Part A;
WMHV=
white matter hyperintensity volume

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received January 28, 2015.
  • Accepted in final form October 27, 2015.
  • © 2016 American Academy of Neurology
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