Abstract | PURPOSE: To develop a relevant pathophysiologic model of human immunodeficiency virus (HIV)-associated dementia by studying regional variations in metabolite levels measured with magnetic resonance (MR) spectroscopic imaging and their relationship to immunologic measures and cognitive dysfunction. MATERIALS AND METHODS: This was a HIPAA-compliant, institutional review board-approved study involving written informed consent. Distributions of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) concentrations in 94 subjects (20 seronegative controls and 74 HIV-positive subjects; 34 of the HIV-positive subjects having HIV-associated dementia; 63 men, 31 women; mean age, 40 years) were determined with proton ( hydrogen 1 [(1)H]) MR spectroscopic imaging. HIV-positive subjects underwent neuropsychological testing and blood and cerebrospinal fluid (CSF) analysis. Factor analysis was utilized to determine associations between metabolites across regions. Analysis of variance and t tests were used to isolate differences between cohorts. RESULTS: A "Cho factor" differentiated seronegative controls from HIV-infected cohorts, indicating elevated Cho levels across deep gray and white matter regions of HIV-positive individuals. An "NAA factor" differentiated those with dementia from those without and correlated best with psychomotor and executive function tests. A "Cr factor" indicated Cr elevations correlated with CSF monocyte chemoattractant protein-1 levels. NAA and Cr factor scores were strongly weighted to metabolite changes in white matter regions. CONCLUSION: These results highlight the importance of white matter involvement in HIV-associated dementia and support the current pathogenesis model of glial cell proliferation in HIV infection, denoted by regional Cho elevations, and neuronal dysfunction and/or death, denoted by NAA decreases, associated with dementia. Factor analysis of MR spectroscopic imaging data is a useful method for determining regional metabolic variations in HIV infection and its neuropsychological correlates.
|
Authors | Mona A Mohamed, Margaret R Lentz, Vallent Lee, Elkan F Halpern, Ned Sacktor, Ola Selnes, Peter B Barker, Martin G Pomper |
Journal | Radiology
(Radiology)
Vol. 254
Issue 2
Pg. 577-86
(Feb 2010)
ISSN: 1527-1315 [Electronic] United States |
PMID | 20093528
(Publication Type: Journal Article)
|
Chemical References |
- Aspartic Acid
- N-acetylaspartate
- Creatine
- Choline
|
Topics |
- AIDS Dementia Complex
(metabolism)
- Adult
- Analysis of Variance
- Aspartic Acid
(analogs & derivatives, metabolism)
- Case-Control Studies
- Chi-Square Distribution
- Choline
(metabolism)
- Creatine
(metabolism)
- Factor Analysis, Statistical
- Female
- HIV Infections
(metabolism)
- Humans
- Magnetic Resonance Spectroscopy
- Male
- Neuropsychological Tests
|