The goals of this project are: (1) to develop more sensitive in vivo measures of the presence and progression of HIV effect on brain function and pathology, and (2) using these measures, to elucidate and quantitate the temporal and spatial patterning of the progression of brain involvement in HIV disease. Such objective measures of effects of HIV on the brain are essential for monitoring the effects of therapeutic interventions on disease pathology and function impairment. Our ongoing studies have documented both structural and functional deficits in cognitively impaired seropositive (CISP) patients, and functional deficits in cognitively impaired seropositive (CNSP) patients. The functional deficits involved increased latency of the frontal P3A component of the brain electrical evoked potential (EP). The structural deficits involved demonstration and replication of antemortem reductions in N-acetylaspartate (NAA) concentrations throughout a supraventricular brain volume using 1H MRSI. This application extends these initial observations, testing the following hypotheses: 1: (a) In cognitively impaired HIV+(CISP) patients compared to HIV-high risk controls, NAA reductions will be largest in the subcortical gray matter, and (b) within the CISP patient group, average NAA concentrations in the subcortical gray matter will be proportional to the severity of neuropsychological impairment and/or the degree of P3A latency prolongation 2: (a) Cognitively normal HIV+(CNSP) patients with relatively long- standing HIV infection, compared to high-risk controls, will demonstrate reductions in subcortical gray matter and (to a lesser extent) deep white matter NAA, and increases in P3A latency; (b) the magnitude of the subcortical gray matter and deep white matter NAA reductions observed will be proportional to the increase in P3A latency. 3. Changes in neuropsychological function over time with HIV disease progression will be associated with decreases in NAA and increases in P3A latency. Positive responses to treatment will be associated with either an arresting of the progression of NAA and P3A changes or with recovery of NAA and P3A deficits.
These specific aims will be accomplished using longitudinal 1H MRSI and EP investigation of 30 CISP and 40 CNSP patients compared to both high- risk and low-risk controls. CISP and CNSP subjects will be studied with replacement of subjects who either die or drop out of the study so that the replicability of results regarding the spatial and temporal patterning of disease progression can be established.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH045680-07
Application #
2033781
Study Section
Psychobiological, Biological, and Neurosciences Subcommittee (MHAI)
Project Start
1990-04-01
Project End
1998-12-31
Budget Start
1997-01-01
Budget End
1997-12-31
Support Year
7
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Nielsen-Bohlman, Lynn; Fein, George; Boyle, Devon et al. (2002) N400 event-related potential reduction indexes: early central nervous system impairment in HIV. J NeuroAIDS 2:51-65
Di Sclafani, V; Mackay, R D; Meyerhoff, D J et al. (1997) Brain atrophy in HIV infection is more strongly associated with CDC clinical stage than with cognitive impairment. J Int Neuropsychol Soc 3:276-87
Nielsen-Bohlman, L; Boyle, D; Biggins, C et al. (1997) Semantic priming impairment in HIV. J Int Neuropsychol Soc 3:348-58
Meyerhoff, D J; Weiner, M W; Fein, G (1996) Deep gray matter structures in HIV infection: a proton MR spectroscopic study. AJNR Am J Neuroradiol 17:973-8
MacKay, S; Meyerhoff, D J; Constans, J M et al. (1996) Regional gray and white matter metabolite differences in subjects with AD, with subcortical ischemic vascular dementia, and elderly controls with 1H magnetic resonance spectroscopic imaging. Arch Neurol 53:167-74
Constans, J M; Meyerhoff, D J; Gerson, J et al. (1995) H-1 MR spectroscopic imaging of white matter signal hyperintensities: Alzheimer disease and ischemic vascular dementia. Radiology 197:517-23
Fein, G; Biggins, C A; MacKay, S (1995) Alcohol abuse and HIV infection have additive effects on frontal cortex function as measured by auditory evoked potential P3A latency. Biol Psychiatry 37:183-95
Constans, J M; Meyerhoff, D J; Norman, D et al. (1995) 1H and 31P magnetic resonance spectroscopic imaging of white matter signal hyperintensity areas in elderly subjects. Neuroradiology 37:615-23
Fein, G; Biggins, C A; MacKay, S (1995) Delayed latency of the event-related brain potential P3A component in HIV disease. Progressive effects with increasing cognitive impairment. Arch Neurol 52:1109-18
Meyerhoff, D J; MacKay, S; Sappey-Marinier, D et al. (1995) Effects of chronic alcohol abuse and HIV infection on brain phosphorus metabolites. Alcohol Clin Exp Res 19:685-92

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