Description
The connection between vascular health, or heart health, and cognition, or memory and thinking, has been of scientific interest for over a century. The weight of the human brain is only 2% of total body weight. Yet, it receives 15% of blood flow, and uses 20% of all the oxygen the body consumes. Currently the scientific community understands that vascular health is one major category of risk factors for Alzheimer’s disease. Research from our group suggests that even modest changes in cardiac output, in other words changes in how much blood the brain receives, are associated with clinically detectable neuropsychological impairment, reduced gray matter volume, increased white matter hyperintensities (WMH), reduced normative cerebral perfusion values, and incident dementia, especially Alzheimer's disease. Alzheimer’s disease and heart disease are in the top six leading causes of death in the US. About 85.6 million Americans are living with some form of cardiovascular disease.
Jefferson, et al., 2007, J Am Geriatr Soc Jefferson, et al., 2015, Circulation
Gifford, et al., 2013, Arch Clin Neuropsychol Jefferson, et al., 2011, Neurobiol Aging
Collectively, research from our group and others suggests vascular health factors are associated with Alzheimer’s disease. Whether this association is causal remains unknown. Three pathways for how vascular health impacts memory are plausible (see figures below). The first, cardiovascular disease (e.g., myocardial infarction, congestive heart failure) may act as a mediator. That is, the presence of cardiovascular disease, rather than any one risk factor (e.g., hypertension), drives the link between vascular risk factors and cognition. The second, heart disease acts as a pathway of injury in the brain. In other words vascular risk factors, such as hypertension and diabetes mellitus, start a pathway of injury to cognition by disrupting the brain’s blood vessels. Over time, vascular risk factor burden can contribute to prevalent cardiovascular disease. Alternatively, and the third possible pathway, it is plausible that no causal pathway exists, and any reported connection between vascular risk factors and abnormal cognitive aging is epiphenomenological, or the interaction between environment and our genes, in nature.
The Vascular Health & Prevention Research Initiative furthers the mission of the Vanderbilt Memory & Alzheimer's Center to advance the scientific community’s understanding of risk factors, early diagnostic markers, prevention and treatment methods for memory loss and unhealthy cognitive aging, including mild cognitive impairment, Alzheimer's disease, and related disorders.
Initiative Leadership
Angela Jefferson, PhD
Director, Vanderbilt Memory & Alzheimer’s Center
Professor of Neurology
Collaborators
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Susan Bell, MBBS, MSCI / Assistant Professor of Medicine at Vanderbilt University Medical Center
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Manus Donahue, PhD / Associate Professor of Radiology at Vanderbilt University Medical Center
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Deepak Gupta, MD / Instructor in Medicine and Physician Scientist in the Vanderbilt Heart and Vascular Institute and Cardiovascular Translational Research Center
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Kimberly Pechman, PhD / Staff Scientist at Vanderbilt Memory & Alzheimer's Center
Current Research Activities
Relevant Publications
2018
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Hohman TJ, Dumitrescu L, Barnes LL, Thambisetty M, Beecham G, Kunkle B, Gifford KA, Bush WS, Chibnik LB, Mukherjee S, De Jager PL, Kukull W, Crane PK, Resnick SM, Keene CD, Montine TJ, Schellenberg GD, Haines JL, Zetterberg H, Blennow K, Larson EB, Johnson SC, Albert M, Bennett DA, Schneider JA, Jefferson AL. Sex-Specific Association of Apolipoprotein E With Cerebrospinal Fluid Levels of Tau. JAMA neurology. 2018 May 7.
2016
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Jefferson AL, Gifford KA, Acosta LM, Bell SP, Donahue MJ, Davis LT, Gottlieb J, Gupta DK, Hohman TJ, Lane EM, Libon DJ, Mendes LA, Niswender K, Pechman KR, Rane S, Ruberg FL, Su YR, Zetterberg H, Liu D. The Vanderbilt Memory & Aging Project: Study Design and Baseline Cohort Overview. Journal of Alzheimer's disease : JAD. 2016 Dec 8;52(52). 539-59. NIHMSID: NIHMS769281.
2015
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ArrayHohman TJ, Samuels LR, Liu D, Gifford KA, Mukherjee S, Benson EM, Abel T, Ruberg FL, Jefferson AL. Stroke risk interacts with Alzheimer's disease biomarkers on brain aging outcomes. Neurobiology of aging. 2015 Sep;36(36). 2501-8.
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Jefferson AL, Gifford KA, Damon S, Chapman GW, Liu D, Sparling J, Dobromyslin V, Salat D. Gray & white matter tissue contrast differentiates Mild Cognitive Impairment converters from non-converters. Brain imaging and behavior. 2015 Jun;9(9). 141-8.
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ArrayHohman TJ, Bell SP, Jefferson AL. The role of vascular endothelial growth factor in neurodegeneration and cognitive decline: exploring interactions with biomarkers of Alzheimer disease. JAMA neurology. 2015 May;72(72). 520-9.
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Jefferson AL, Beiser AS, Himali JJ, Seshadri S, O'Donnell CJ, Manning WJ, Wolf PA, Au R, Benjamin EJ. Low cardiac index is associated with incident dementia and Alzheimer disease: the Framingham Heart Study. Circulation. 2015 Apr 14;131(131). 1333-9.
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Jefferson AL, Hohman TJ, Liu D, Haj-Hassan S, Gifford KA, Benson EM, Skinner JS, Lu Z, Sparling J, Sumner EC, Bell S, Ruberg FL. Adverse vascular risk is related to cognitive decline in older adults. Journal of Alzheimer's disease : JAD. 44(44). 1361-73.
2014
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Jefferson AL. Vascular risk factors and midlife cognition: rethinking the exposure window. Circulation. 2014 Apr 15;129(129). 1548-50.
2011
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Jefferson AL, Himali JJ, Au R, Seshadri S, Decarli C, O'Donnell CJ, Wolf PA, Manning WJ, Beiser AS, Benjamin EJ. Relation of left ventricular ejection fraction to cognitive aging (from the Framingham Heart Study). The American journal of cardiology. 2011 Nov 1;108(108). 1346-51.
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Jefferson AL, Massaro JM, Beiser AS, Seshadri S, Larson MG, Wolf PA, Au R, Benjamin EJ. Inflammatory markers and neuropsychological functioning: the Framingham Heart Study. Neuroepidemiology. 37(37). 21-30.
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Jefferson AL, Holland CM, Tate DF, Csapo I, Poppas A, Cohen RA, Guttmann CR. Atlas-derived perfusion correlates of white matter hyperintensities in patients with reduced cardiac output. Neurobiology of aging. 2011 Jan;32(32). 133-9.
2010
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Jefferson AL, Himali JJ, Beiser AS, Au R, Massaro JM, Seshadri S, Gona P, Salton CJ, DeCarli C, O'Donnell CJ, Benjamin EJ, Wolf PA, Manning WJ. Cardiac index is associated with brain aging: the Framingham Heart Study. Circulation. 2010 Aug 17;122(122). 690-7.
2007
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Jefferson AL, Tate DF, Poppas A, Brickman AM, Paul RH, Gunstad J, Cohen RA. Lower cardiac output is associated with greater white matter hyperintensities in older adults with cardiovascular disease. Journal of the American Geriatrics Society. 2007 Jul;55(55). 1044-8.
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Jefferson AL, Massaro JM, Wolf PA, Seshadri S, Au R, Vasan RS, Larson MG, Meigs JB, Keaney JF, Lipinska I, Kathiresan S, Benjamin EJ, DeCarli C. Inflammatory biomarkers are associated with total brain volume: the Framingham Heart Study. Neurology. 2007 Mar 27;68(68). 1032-8.