Hypertension, dyslipidemia, hyperinsulinemia, glucose intolerance, and abdominal adiposity are facets of the metabolic syndrome, and are predictors of stroke and vascular dementia. Prior to overt cerebrovascular disease, subtle cognitive deficits are noted in persons with these cardiovascular (CV) risk factors. However, the biological mechanisms linking CV risk factors to poorer cognitive function are poorly understood. Subtle deficits in cognitive function and accompanying brain abnormalities may constitute early markers of elevated cerebrovascular risk among older adults with CV risk factors. The first specific aim of this competing continuation project is to examine whether, in 250 stroke-free, non-demented and non-diabetic older adults (ages 60-80+), 90 from our initial R29 project combined with 160 from this proposed project, CV risk factors - systolic and diastolic blood pressure, blood glucose, insulin, dyslipidemia, and abdominal adiposity - are associated with the poorer outcomes on: (1) neuropsychological test performance; (2) magnetic resonance imaging (MRI) ratings of white matter hyperintensities, silent infarction, and brain atrophy; (3) magnetic resonance angiography (MRA) ratings of stenosis of the large cerebral and cervicocerebral arteries; and (4) relative ratios of cerebral:cerebellar perfusion as assessed by single photon emission computed tomography (SPECT). The second specific aim is to examine whether MRI, MRA, and SPECT indices of subtle brain abnormalities mediate the relation between CV risk factors and poorer cognitive function. The cumulative burden of the CV risk factors and brain abnormalities will be examined in relation to domains of cognitive function, as will individual risk factors and brain abnormalities. To our knowledge, this will be the first study to examine whether several interrelated CV risk factors are associated with diminished cognitive function via several biologically plausible brain mechanisms in otherwise healthy older adults. Structural equation modeling will be used to examine patterns of interrelations among these variables and directly test brain abnormalities as potential mediators of the CV risk factor-cognition relation. Understanding the pathogenesis of cognitive impairment associated with CV risk factors in older adults may lead to enhanced efforts in prevention and intervention to reduce cerebrovascular risk, preserve cognitive functioning, and improve quality of life.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
2R01AG015112-06
Application #
6777830
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Wagster, Molly V
Project Start
2004-09-30
Project End
2009-07-30
Budget Start
2004-09-30
Budget End
2005-07-30
Support Year
6
Fiscal Year
2004
Total Cost
$268,720
Indirect Cost
Name
University of Maryland Balt CO Campus
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
061364808
City
Baltimore
State
MD
Country
United States
Zip Code
21250
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Sims Wright, Regina; Levy, Shellie-Anne T; Katzel, Leslie I et al. (2015) Fasting glucose and glucose tolerance as potential predictors of neurocognitive function among nondiabetic older adults. J Clin Exp Neuropsychol 37:49-60
Sims, R C; Katzel, L I; Lefkowitz, D M et al. (2014) Association of fasting glucose with subclinical cerebrovascular disease in older adults without Type 2 diabetes. Diabet Med 31:691-8
Sims, Regina C; Hosey, Megan; Levy, Shellie-Anne et al. (2014) Distinct functions of social support and cognitive function among older adults. Exp Aging Res 40:40-59
Spencer, Robert J; Wendell, Carrington R; Giggey, Paul P et al. (2013) Psychometric limitations of the mini-mental state examination among nondemented older adults: an evaluation of neurocognitive and magnetic resonance imaging correlates. Exp Aging Res 39:382-97
Spencer, Robert J; Wendell, Carrington R; Giggey, Paul P et al. (2013) Judgment of Line Orientation: an examination of eight short forms. J Clin Exp Neuropsychol 35:160-6
Waldstein, Shari R; Wendell, Carrington R; Lefkowitz, David M et al. (2012) Interactive relations of blood pressure and age to subclinical cerebrovascular disease. J Hypertens 30:2352-6
Wendell, Carrington Rice; Hosey, Megan M; Lefkowitz, David M et al. (2010) Depressive symptoms are associated with subclinical cerebrovascular disease among healthy older women, not men. Am J Geriatr Psychiatry 18:940-7
Waldstein, Shari R; Lefkowitz, David M; Siegel, Eliot L et al. (2010) Reduced cerebral blood flow in older men with higher levels of blood pressure. J Hypertens 28:993-8

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