Chronic diseases, which increase in prevalence with age, impair intellectual functioning. It has been shown that patients with essential hypertension have impaired performance on neuropsychological tests relative to age-matched controls. The mechanism by which hypertension impairs intellectual function is unknown. A likely possibility is that hypertension induces changes in the cerebral vasculature which are responsible for the neuropsychological impairments. Hypertension induces morphological changes (vascular remodeling) which may interfere with regional cerebral blood flow (rCBF) responses induced by information processing. Positron Emission Tomography (PET) functional brain imaging permits the investigators to test the hypothesis that hypertension impairs the rCBF response. With the advent of ultrasound measurements of the carotid arteries, the investigators can also test a second hypothesis that atherosclerosis influences intellectual function. This second hypothesis is considered because of the results available from the Kuopio Ischemic Heart Disease Study. Extent of carotid atherosclerosis was negatively related to intellectual functioning. Given that atherosclerosis could not be assessed in earlier studies of hypertension, it may be that only atherosclerosis is uniquely associated with intellectual impairments. Alternatively, heightened blood pressure and atherosclerosis may independently or interactively induce impairment. The investigators propose a project to test the hypothesis that hypertension alters neuropsychological function by damping the rCBF response to metabolic need created during information processing; and that carotid atherosclerosis adds to these impairments via the same mechanism. Measures of white matter lesions are also obtained to see if these may mediate the influences of hypertension and atherosclerosis. The hypothesis is tested by computing the contribution that hypertension and carotid atherosclerosis make directly and interactively to neuropsychological performance and rCBF in selected regions activated by performance tasks. The project attempts to identify mechanisms for how diseases of aging influence intellectual functioning. Successful completion will clarify a) how aging and the diseases of aging reduce intellectual functioning, and b) ultimately permit a rational choice of clinical regimen to treat the diseases of aging while minimizing neuropsychological side effects.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL057529-03
Application #
6043942
Study Section
Behavioral Medicine Study Section (BEM)
Project Start
1997-08-01
Project End
2001-07-31
Budget Start
1999-08-01
Budget End
2000-07-31
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Jennings, J Richard; Heim, Alicia F; Kuan, Dora Chieh-Hsin et al. (2013) Use of total cerebral blood flow as an imaging biomarker of known cardiovascular risks. Stroke 44:2480-5
Heim, Alicia F; Coyne, Melissa J; Kamboh, M Ilyas et al. (2013) The catechol-o-methyltransferase Val158 Met polymorphism modulates organization of regional cerebral blood flow response to working memory in adults. Int J Psychophysiol 90:149-56
Jennings, J R; Mendelson, D N; Muldoon, M F et al. (2012) Regional grey matter shrinks in hypertensive individuals despite successful lowering of blood pressure. J Hum Hypertens 26:295-305
Jennings, J Richard; Mendelson, David N; Redfern, Mark S et al. (2011) Detecting age differences in resistance to perceptual and motor interference. Exp Aging Res 37:179-97
Richard Jennings, J; Christie, Israel C; Muldoon, Matthew F et al. (2010) Brain function, cognition, and the blood pressure response to pharmacological treatment. Psychosom Med 72:702-11
Jennings, J Richard; Zanstra, Ydwine (2009) Is the brain the essential in hypertension? Neuroimage 47:914-21
Jennings, J Richard; Muldoon, Matthew F; Whyte, Ellen M et al. (2008) Brain imaging findings predict blood pressure response to pharmacological treatment. Hypertension 52:1113-9
Jennings, J Richard; Muldoon, Matthew F; Price, Julie et al. (2008) Cerebrovascular support for cognitive processing in hypertensive patients is altered by blood pressure treatment. Hypertension 52:65-71
Christie, Israel C; Price, Julie; Edwards, Louisa et al. (2008) Alcohol consumption and cerebral blood flow among older adults. Alcohol 42:269-75
Jennings, J Richard; van der Veen, Frederik M; Meltzer, Carolyn C (2006) Verbal and spatial working memory in older individuals: A positron emission tomography study. Brain Res 1092:177-89

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