Proton MRS and neuropsychological correlates in AIDS dementia complex: Evidence of subcortical specificity

Few studies have described the metabolic substrates underlying neuropsychological performance in HIV infection or examined the specificity of these relationships. The authors performed magnetic resonance spectroscopic and neuropsychological evaluations on 61 patients with AIDS dementia complex (stages 1-3) and 39 HIV-positive neurologically asymptomatic individuals. N-acetylaspartate, a marker of mature neurons, choline and myoinositol, both markers of gliosis, and creatine, a reference marker, were measured in the basal ganglia, frontal white matter, and parietal cortex. The neuropsychological evaluation consisted of tests that measured gross and fine motor skills, psychomotor function, information processing speed, and verbal memory. The authors examined performance on individual subtests and an aggregate Z score based on eight subtests (NPZ-8), adjusted for age and education. The NPZ-8 was significantly higher in subjects with greater N-acetylaspartate/creatine in the frontal white matter and was lower in subjects with higher myoinositol/creatine in the basal ganglia. Particularly strong associations were found between measures of gross and fine motor function, which correlated positively with N-acetylaspartate/creatine in the frontal white matter and negatively with myoinositol/creatine in the basal ganglia. Similarly, cognitive processing speed was negatively correlated with myoinositol/creatine in the basal ganglia. In contrast, there were no statistically significant relationships between brain metabolite levels in the parietal cortex and neuropsychological function. This study provides convincing evidence that neuropsychological impairment is associated with reduced markers of mature neurons and increased markers of gliosis in the basal ganglia and frontal white matter. Neural changes as reflected by these metabolite levels may prove useful in identifying individuals at risk for neuropsychological impairment. Prospective studies are needed to elucidate the evolution of these changes in the setting of antiretroviral therapy.