Background and Purpose HIV-associated dementia (HAD) has been extensively studied using magnetic resonance spectroscopy (MRS) at field strengths of 1.5 Tesla (T). Higher magnetic field strengths (such as 3T) allow for more reliable determination of certain compounds, such as glutamate (Glu) and glutamine (Gln). The current study was undertaken to investigate the utility of 3T MRS for evaluating HIV+ patients with different levels of cognitive impairment with emphasis on the measurement of Glu and Glx (the sum of Glu and Gln). Methods Eighty six HIV+ subjects were evaluated at 3T using quantitative short echo time single voxel MRS of frontal white matter (FWM) and basal ganglia (BG). Subjects were divided into 3 groups according to the Memorial Sloan Kettering (MSK) HIV dementia stage: 21 had normal cognition (NC) (MSK 0), 31 had mild cognitive impairment (MCI) without dementia, (clinical MSK stage = 0.5) and 34 had dementia (HAD) (MSK > 1). HIV+ subjects had also undergone standardized cognitive testing covering the domains of executive function, verbal memory, attention, information processing speed, and motor and psychomotor speed. Between group differences in metabolite levels in FWM and BG were evaluated using ANOVA. Pearson correlation coefficients were used to explore the associations between the Glu and Glx metabolites and neurocognitive (NP) results. Results FWM Glx (combined Glu and Gln) was lower in HAD (8.1±2.1 mM) compared to both the MCI (9.17±2.1 mM) and NC groups (10.0±1.6 mM), (P = 0.006). FWM myo-inositol (mI) was higher in HAD (4.15±0.75 mM) compared to both MCI (3.86±0.85 mM) and NC status (3.4±0.67 mM), (P = 0.006). FWM Glx/Creatine (Cr) was lower and FWM mI/Cr significantly higher in the HAD compared to MCI and NC groups (P = 0.01) and (P = 0.004) respectively. BG NAA was lower in the HAD group (6.79±1.53 mM), compared to the MCI (7.5±1.06 mM), and NC groups (7.6±1.01 mM), (P = 0.036). Significant negative correlations were observed between Glu, Glx, and NAA concentrations with Trail-making test B (P= 0.006, 0.0001, and 0.007 respectively) and significant positive correlation was found with Digit symbol test (P= 0.02, 0.002, and 0.008 respectively). FWM Glx and NAA concentrations showed negative correlation with Grooved pegboard non-dominant hand (P= 0.02 and 0.04 respectively). Conclusion Patients with HAD have lower levels of Glx concentrations and Glx/Cr ratio in FWM, which was associated with impaired performance in specific cognitive domains, including executive functioning, fine motor, attention and working memory performance. 3T MRS measurements of Glx may be a useful indicator of neuronal loss/dysfunction in patients with HIV infection.

A B S T R A C T A reduction in the release of substrate amino acids from skeletal muscle largely explains the decrease in gluconeogenesis characterizing prolonged starvation. Brief starvation is associated with an increase in gluconeogenesis, suggesting increased release of amino acids from muscle. In the present studies, accelerated amino acid release from skeletal muscle induced by brief starvation was sought to account for the accompanying augmentation of gluconeogenesis. To do this amino acid balance across forearm muscles was quantified in 15 postabsorptive (overnight fasted) subjects and in 7 subjects fasted for 60 h.Fasting significantly reduced basal insulin (11.3-7.5 /AU/ml) and increased glucagon (116-134 pg/ml).Muscle release of the principal glycogenic amino acids increased. Alanine release increased 59.4%. The increase in release for all amino acids averaged 69.4% and was statistically significant for threonine, serine, glycine, alanine, a-aminobutyrate, methionine, tyrosine, and lysine. Thus, with brief starvation, muscle release of glycogenic amino acids increases strikingly. This contrasts with the reduction in amino acid release characterizing prolonged starvation. The adaptation of peripheral tissue metabolism to brief starvation is best explained by the decrease in insulin.

The objectives of this study are to compare the results of newer performance-based functional assessments in the study of HIV-associated neurocognitive disorders (HAND) and to correlate these functional assessments with specific levels of severity of HAND. One hundred fourteen HIV+ subjects in an existing cohort were evaluated with a medical history, neurological exam, neuropsychological test battery as well as subjective and novel objective measures of functional abilities. Self-reported measures of functional performance included the Karnofsky Performance Scale, a questionnaire for instrumental activities of daily living, and a questionnaire for physical quality of life measures. The newer objective functional performance assessments in cluded the Columbia Medication Management and the San Diego Finances tests. These newer performance-based measures of function were assessed for their ability to predict level of HAND. The two objective measures of functional performance, The Columbia Medication Management Scale and the San Diego Finances Test, were both associated with levels of severity of HAND. The Karnofsky Performance Scale and the questionnaires for role and physical quality of life were subjective measures that were also associated with specific levels of HAND. Newer measures of functional performance can be used to objectively evaluate functional impairment in HAND and validate different levels of HAND.