7T Brain MRS in HIV Infection: Correlation with Cognitive Impairment and Performance on Neuropsychological Tests

Abstract

Background and Purpose 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 MRS measurements related to neuronal health and function (particularly N-acetylaspartate (NAA) and glutamate (Glu)) would be lower in HIV+ subjects with worse cognitive performance. Materials and Methods 45 HIV+ patients [58.9 ± 5.3 years; 33 male] underwent detailed neuropsychological (NP) testing and brain MRS at 7 Tesla. 24 subjects were classified as having asymptomatic cognitive impairment and 21 were classified as symptomatic cognitive impairment. Single voxel proton MR spectra were acquired from 5 brain regions and quantified using ‘LCModel’ software. Brain metabolites and NP test results were compared using non-parametric statistics and Pearson correlation coefficients. Results Significant differences in brain metabolites were found between symptomatic and asymptomatic subjects, with the main findings being lower measures of N-acetyl aspartate (NAA) in the frontal white matter (FWM), posterior cingulate cortex (PCC), and precuneus (PC). In the PC, glutamate (Glu) was also lower in the symptomatic group. In the FWM, PC and PCC, NAA and Glu measurements showed significant positive correlation with better performance on NP tests. Conclusion Compared to asymptomatic, symptomatic HIV+ subjects had lower levels of NAA and Glu, most notably in frontal white matter, which also correlated with performance on neuropsychological tests. High field MRS offers insights into the pathophysiology associated with cognitive impairment in HIV, and may be useful as a quantitative outcome measure in future treatment trials.

Meta-analysis of brain metabolite differences in HIV infection

“…Better understanding the relationship of metabolite differences to cognitive function in HIV infection might provide insight into the mechanisms of associated cognitive impairment. Lower tNAA/tCr levels are associated with poorer neuropsychological performance in HIV infected individuals ( Mohamed et al, 2018 , Laubenberger et al, 1996 ). Lower WM tNAA/tCr has been associated with worse performance on measures of executive function, fine motor, and psychomotor speed ( Mohamed et al, 2018 ).…”

“…Lower tNAA/tCr levels are associated with poorer neuropsychological performance in HIV infected individuals ( Mohamed et al, 2018 , Laubenberger et al, 1996 ). Lower WM tNAA/tCr has been associated with worse performance on measures of executive function, fine motor, and psychomotor speed ( Mohamed et al, 2018 ). Lower tNAA/tCr in the posterior cingulate cortex was associated with poorer performance on tests of psychomotor speed and lower precuneus tNAA/tCr was associated with worse performance on the Stroop Test, a test of processing speed and attention ( Mohamed et al, 2018 ).…”

“…Lower WM tNAA/tCr has been associated with worse performance on measures of executive function, fine motor, and psychomotor speed ( Mohamed et al, 2018 ). Lower tNAA/tCr in the posterior cingulate cortex was associated with poorer performance on tests of psychomotor speed and lower precuneus tNAA/tCr was associated with worse performance on the Stroop Test, a test of processing speed and attention ( Mohamed et al, 2018 ). tNAA reductions have also correlated with poorer cognition in other neurological diseases such as vascular cognitive impairment ( Gasparovic et al, 2013 ) and Alzheimer’s disease ( Godbolt et al, 2006 ).…”

Use of Neuroimaging to Inform Optimal Neurocognitive Criteria for Detecting HIV-Associated Brain Abnormalities

“…Magnetic resonance spectroscopy (MRS) studies demonstrate cerebral metabolic abnormalities indicative of neuroinflammation (e.g., elevated choline and myo-inositol) and neuronal loss (e.g., reduced N-acetyl-aspartate and glutamate) across cortical and subcortical tissues (Chang et al, 2004;Cysique et al, 2013;Ernst, Jiang, Nakama, Buchthal, & Chang, 2010;Harezlak et al, 2011;Paul et al, 2008). PLWH with the greatest evidence of neuroinflammation and neuronal loss are at higher risk for HAND, with decrements executive function, working memory, learning, recall, and complex motor skills (Ernst et al, 2010;Mohamed, Barker, Skolasky, & Sacktor, 2018;Paul et al, 2008). Given these findings, some authors have advocated for the inclusion of neuroimaging biomarkers in HAND diagnostic decision-making (Ances & Hammoud, 2014;Masters & Ances, 2014;Saloner & Cysique, 2017).…”

Distinguishing Brain Impact of Aging and HIV Severity in Chronic HIV Using Multiparametric MR Imaging and MR Spectroscopy

“…In work by Mohamed et al, HIV+ participants were treated but had persistent viremia [ 14 ] and nearly half had HIV-associated dementia. In more recent studies, creatine alterations have been seen in individuals who have recently started therapy [ 16 ]. In contrast, our population had had effective viral suppression for a year or more.…”