M Mohamed1, P B Barker2,3,4, R L Skolasky5,6, N Sacktor5. 1. From the Russell H. Morgan Department of Radiology and Radiological Science (M.M., P.B.B.) mnourel1@jhmi.edu. 2. From the Russell H. Morgan Department of Radiology and Radiological Science (M.M., P.B.B.). 3. Psychiatry and Behavioral Sciences (P.B.B.), Johns Hopkins University School of Medicine, Baltimore, Maryland. 4. F.M. Kirby Center for Functional Brain Imaging (P.B.B.), Kennedy Krieger Institute, Baltimore, Maryland. 5. Departments of Neurology (R.L.S., N.S.). 6. Orthopedic Surgery (R.L.S.).
Abstract
BACKGROUND AND PURPOSE: Validated neuroimaging markers of HIV-associated neurocognitive disorder in patients on antiretroviral therapy are urgently needed for clinical trials. The purpose of this study was to explore the relationship between cognitive impairment and brain metabolism in older subjects with HIV infection. It was hypothesized that MR spectroscopy measurements related to neuronal health and function (particularly N-acetylaspartate and glutamate) would be lower in HIV-positive subjects with worse cognitive performance. MATERIALS AND METHODS: Forty-five HIV-positive patients (mean age, 58.9 ± 5.3 years; 33 men) underwent detailed neuropsychological testing and brain MR spectroscopy at 7T. Twenty-four subjects were classified as having asymptomatic cognitive impairment, and 21 were classified as having symptomatic cognitive impairment. Single-voxel proton MR spectra were acquired from 5 brain regions and quantified using LCModel software. Brain metabolites and neuropsychological test results were compared using nonparametric statistics and Pearson correlation coefficients. RESULTS: Differences in brain metabolites were found between symptomatic and asymptomatic subjects, with the main findings being lower measures of N-acetylaspartate in the frontal white matter, posterior cingulate cortex, and precuneus. In the precuneus, glutamate was also lower in the symptomatic group. In the frontal white matter, precuneus, and posterior cingulate cortex, NAA and glutamate measurements showed significant positive correlation with better performance on neuropsychological tests. CONCLUSIONS: Compared with asymptomatic subjects, symptomatic HIV-positive subjects had lower levels of NAA and glutamate, most notably in the frontal white matter, which also correlated with performance on neuropsychological tests. High-field MR spectroscopy offers insight into the pathophysiology associated with cognitive impairment in HIV and may be useful as a quantitative outcome measure in future treatment trials.
BACKGROUND AND PURPOSE: Validated neuroimaging markers of HIV-associated neurocognitive disorder in patients on antiretroviral therapy are urgently needed for clinical trials. The purpose of this study was to explore the relationship between cognitive impairment and brain metabolism in older subjects with HIV infection. It was hypothesized that MR spectroscopy measurements related to neuronal health and function (particularly N-acetylaspartate and glutamate) would be lower in HIV-positive subjects with worse cognitive performance. MATERIALS AND METHODS: Forty-five HIV-positive patients (mean age, 58.9 ± 5.3 years; 33 men) underwent detailed neuropsychological testing and brain MR spectroscopy at 7T. Twenty-four subjects were classified as having asymptomatic cognitive impairment, and 21 were classified as having symptomatic cognitive impairment. Single-voxel proton MR spectra were acquired from 5 brain regions and quantified using LCModel software. Brain metabolites and neuropsychological test results were compared using nonparametric statistics and Pearson correlation coefficients. RESULTS: Differences in brain metabolites were found between symptomatic and asymptomatic subjects, with the main findings being lower measures of N-acetylaspartate in the frontal white matter, posterior cingulate cortex, and precuneus. In the precuneus, glutamate was also lower in the symptomatic group. In the frontal white matter, precuneus, and posterior cingulate cortex, NAA and glutamate measurements showed significant positive correlation with better performance on neuropsychological tests. CONCLUSIONS: Compared with asymptomatic subjects, symptomatic HIV-positive subjects had lower levels of NAA and glutamate, most notably in the frontal white matter, which also correlated with performance on neuropsychological tests. High-field MR spectroscopy offers insight into the pathophysiology associated with cognitive impairment in HIV and may be useful as a quantitative outcome measure in future treatment trials.
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