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October 16, 2018; 91 (16) Article

Vascular risk at younger ages most strongly associates with current and future brain volume

Matthew P. Pase, Kendra Davis-Plourde, Jayandra J. Himali, Claudia L. Satizabal, Hugo Aparicio, Sudha Seshadri, Alexa S. Beiser, Charles DeCarli
First published September 19, 2018, DOI: https://doi.org/10.1212/WNL.0000000000006360
Matthew P. Pase
From the Melbourne Dementia Research Centre (M.P.P.), the Florey Institute for Neuroscience and Mental Health, the University of Melbourne, Australia; Department of Neurology (M.P.P., J.J.H., C.L.S., H.A., S.S., A.S.B), Boston University School of Medicine; Framingham Heart Study (M.P.P., K.D-.P., J.J.H., H.A., S.S., A.S.B., C.D.), MA; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Australia; Department of Biostatistics (K.D.-P., J.J.H., A.S.B.), Boston University School of Public Health, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S., C.D.), University of Texas Health Sciences Center, San Antonio; and Department of Neurology, School of Medicine & Imaging of Dementia and Aging Laboratory, Center for Neuroscience, University of California Davis, Sacramento.
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Kendra Davis-Plourde
From the Melbourne Dementia Research Centre (M.P.P.), the Florey Institute for Neuroscience and Mental Health, the University of Melbourne, Australia; Department of Neurology (M.P.P., J.J.H., C.L.S., H.A., S.S., A.S.B), Boston University School of Medicine; Framingham Heart Study (M.P.P., K.D-.P., J.J.H., H.A., S.S., A.S.B., C.D.), MA; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Australia; Department of Biostatistics (K.D.-P., J.J.H., A.S.B.), Boston University School of Public Health, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S., C.D.), University of Texas Health Sciences Center, San Antonio; and Department of Neurology, School of Medicine & Imaging of Dementia and Aging Laboratory, Center for Neuroscience, University of California Davis, Sacramento.
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Jayandra J. Himali
From the Melbourne Dementia Research Centre (M.P.P.), the Florey Institute for Neuroscience and Mental Health, the University of Melbourne, Australia; Department of Neurology (M.P.P., J.J.H., C.L.S., H.A., S.S., A.S.B), Boston University School of Medicine; Framingham Heart Study (M.P.P., K.D-.P., J.J.H., H.A., S.S., A.S.B., C.D.), MA; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Australia; Department of Biostatistics (K.D.-P., J.J.H., A.S.B.), Boston University School of Public Health, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S., C.D.), University of Texas Health Sciences Center, San Antonio; and Department of Neurology, School of Medicine & Imaging of Dementia and Aging Laboratory, Center for Neuroscience, University of California Davis, Sacramento.
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Claudia L. Satizabal
From the Melbourne Dementia Research Centre (M.P.P.), the Florey Institute for Neuroscience and Mental Health, the University of Melbourne, Australia; Department of Neurology (M.P.P., J.J.H., C.L.S., H.A., S.S., A.S.B), Boston University School of Medicine; Framingham Heart Study (M.P.P., K.D-.P., J.J.H., H.A., S.S., A.S.B., C.D.), MA; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Australia; Department of Biostatistics (K.D.-P., J.J.H., A.S.B.), Boston University School of Public Health, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S., C.D.), University of Texas Health Sciences Center, San Antonio; and Department of Neurology, School of Medicine & Imaging of Dementia and Aging Laboratory, Center for Neuroscience, University of California Davis, Sacramento.
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Hugo Aparicio
From the Melbourne Dementia Research Centre (M.P.P.), the Florey Institute for Neuroscience and Mental Health, the University of Melbourne, Australia; Department of Neurology (M.P.P., J.J.H., C.L.S., H.A., S.S., A.S.B), Boston University School of Medicine; Framingham Heart Study (M.P.P., K.D-.P., J.J.H., H.A., S.S., A.S.B., C.D.), MA; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Australia; Department of Biostatistics (K.D.-P., J.J.H., A.S.B.), Boston University School of Public Health, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S., C.D.), University of Texas Health Sciences Center, San Antonio; and Department of Neurology, School of Medicine & Imaging of Dementia and Aging Laboratory, Center for Neuroscience, University of California Davis, Sacramento.
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Sudha Seshadri
From the Melbourne Dementia Research Centre (M.P.P.), the Florey Institute for Neuroscience and Mental Health, the University of Melbourne, Australia; Department of Neurology (M.P.P., J.J.H., C.L.S., H.A., S.S., A.S.B), Boston University School of Medicine; Framingham Heart Study (M.P.P., K.D-.P., J.J.H., H.A., S.S., A.S.B., C.D.), MA; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Australia; Department of Biostatistics (K.D.-P., J.J.H., A.S.B.), Boston University School of Public Health, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S., C.D.), University of Texas Health Sciences Center, San Antonio; and Department of Neurology, School of Medicine & Imaging of Dementia and Aging Laboratory, Center for Neuroscience, University of California Davis, Sacramento.
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Alexa S. Beiser
From the Melbourne Dementia Research Centre (M.P.P.), the Florey Institute for Neuroscience and Mental Health, the University of Melbourne, Australia; Department of Neurology (M.P.P., J.J.H., C.L.S., H.A., S.S., A.S.B), Boston University School of Medicine; Framingham Heart Study (M.P.P., K.D-.P., J.J.H., H.A., S.S., A.S.B., C.D.), MA; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Australia; Department of Biostatistics (K.D.-P., J.J.H., A.S.B.), Boston University School of Public Health, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S., C.D.), University of Texas Health Sciences Center, San Antonio; and Department of Neurology, School of Medicine & Imaging of Dementia and Aging Laboratory, Center for Neuroscience, University of California Davis, Sacramento.
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Charles DeCarli
From the Melbourne Dementia Research Centre (M.P.P.), the Florey Institute for Neuroscience and Mental Health, the University of Melbourne, Australia; Department of Neurology (M.P.P., J.J.H., C.L.S., H.A., S.S., A.S.B), Boston University School of Medicine; Framingham Heart Study (M.P.P., K.D-.P., J.J.H., H.A., S.S., A.S.B., C.D.), MA; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Australia; Department of Biostatistics (K.D.-P., J.J.H., A.S.B.), Boston University School of Public Health, MA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases (C.L.S., S.S., C.D.), University of Texas Health Sciences Center, San Antonio; and Department of Neurology, School of Medicine & Imaging of Dementia and Aging Laboratory, Center for Neuroscience, University of California Davis, Sacramento.
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Vascular risk at younger ages most strongly associates with current and future brain volume
Matthew P. Pase, Kendra Davis-Plourde, Jayandra J. Himali, Claudia L. Satizabal, Hugo Aparicio, Sudha Seshadri, Alexa S. Beiser, Charles DeCarli
Neurology Oct 2018, 91 (16) e1479-e1486; DOI: 10.1212/WNL.0000000000006360

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Abstract

Objective Given the potential therapeutic effect of vascular disease control timing to reduce dementia risk, we investigated the age-related influences of vascular risk factor burden on brain structure throughout the lifespan.

Methods We studied participants from the community-based prospective Framingham Heart Study. Overall vascular risk factor burden was calculated according to the Framingham Stroke Risk Profile, a validated algorithm that predicts stroke risk. Brain volume was estimated by MRI. We used cross-sectional data to examine how the strength of association between vascular risk factor burden and brain volume changed across each age decade from age 45–54 years through to 85–94 years (N = 2,887). Second, we leveraged up to 40 years of longitudinal data to determine how the strength of association between vascular risk factor burden and brain volume changed when vascular risk factors were examined at progressively earlier ages (N = 7,868).

Results In both cross-sectional and longitudinal analyses, higher vascular risk factor burden was associated with lower brain volume across each age decade. In the cross-sectional analysis, the strength of this association decreased with each decade of advancing age (p for trend < 0.0001). In longitudinal analysis, the strength of association between vascular risk factor burden and brain volume was stronger when vascular risk factors were measured at younger ages. For example, vascular risk factor burden was most strongly associated with lower brain volume in later life when vascular risk factors were measured at age 45 years.

Conclusion Vascular risk factors at younger ages appear to have detrimental effects on current and future brain volume.

Glossary

FSRP=
Framingham Stroke Risk Profile;
FHS=
Framingham Heart Study

Footnotes

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

  • ↵* Joint senior authors.

  • Editorial page 729

  • Received March 1, 2018.
  • Accepted in final form July 9, 2018.
  • © 2018 American Academy of Neurology
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