Lower Brain Glutamate Is Associated With Cognitive Deficits in HIV Patients: A New Mechanism for HIV-Associated Neurocognitive Disorder

Purpose: To determine whether subjects with human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) show altered concentrations of brain glutamate (GLU), and whether lower GLU levels correlate with cognitive deficits. Materials and Methods: GLU concentrations were measured in the basal ganglia, frontal gray and white matter, and parietal gray matter of 45 HIV-positive and 46 age-and-education-matched HIV-negative subjects using echo-time averaged proton magnetic resonance spectroscopy (H-1 MRS). Results: Compared to controls, HIV subjects with cognitive deficits had lower GLU in the parietal gray matter, while those without cognitive deficits tended to show higher basal ganglia GLU. Lower parietal and frontal gray matter GLU were associated with a greater number of nucleoside reverse transcriptase inhibitors, and were predictive of poorer cognitive performance. Correlations between GLU and cognitive performance, but not the other findings, remained significant after correction for multiple comparisons. Conclusion: Parietal gray matter GLU is lower in HIV subjects with cognitive deficits. This reduction might result from reduced astrocytic reuptake of GLU, secondary excitotoxicity. and mitochondrial toxicity from antiretroviral treatments. The glutarnatergic system may play an important role in the pathophysiology of HAND, and brain GLU on H-1 MRS may provide an early surrogate marker for monitoring disease severity and treatment effects.