title: Relationships among brain metabolites, cognitive function, and viral loads in antiretroviral-naïve HIV patients.
abstract: This study aims to determine the relationship among cerebral metabolite concentrations (on proton magnetic resonance spectroscopy or (1)H MRS), cognitive function, and clinical variables (CD4, plasma and CSF viral loads, and lipids) in antiretroviral medication-nai;ve HIV patients. We hypothesized that the probable glial markers myo-inositol [MI] and choline compounds [CHO] would correlate with cognitive function, CD4 count, and viral loads, but not with serum lipids. Forty-five antiretroviral-drug-nai;ve HIV patients and 25 control subjects were evaluated. Frontal lobe [MI], [CHO], and total creatine [CR] were elevated, while basal ganglia [CR] were decreased, with increasing dementia severity. As a group, HIV patients showed slowing on fine motor (Grooved Pegboard) and psychomotor function (Trails A & B), and deficits on executive function (Stroop tasks). Lower CD4 counts and elevated plasma viral loads were associated with elevated frontal white matter [MI], which in turn correlated with the Stroop tasks. These findings suggest that systemic factors (resulting from suppressed immune function and higher plasma viral load) may lead to glial proliferation (elevated [MI], [CHO], and [CR]) in the frontal white matter, which in turn may contribute to deficits on executive function in HIV. Studying antiretroviral-nai;ve patients minimized the confounding effects of antiretroviral treatment on the clinical, MRS, and neuropsychological variables, and allowed for a more accurate assessment of the relationships among these measurements. Metabolite concentrations, rather than metabolite ratios, should be measured since [CR], a commonly used reference for metabolite ratios, varies with disease severity in both frontal lobe and basal ganglia.
authors.affiliation: Medical Department, Brookhaven National Laboratory, Upton, New York 11973-5000, USA. ChangL@bnl.gov
authors.forename: Linda
authors.initials: L
authors.lastname: Chang
authors.forename: Thomas
authors.initials: T
authors.lastname: Ernst
authors.forename: Mallory D
authors.initials: MD
authors.lastname: Witt
authors.forename: Nina
authors.initials: N
authors.lastname: Ames
authors.forename: Megan
authors.initials: M
authors.lastname: Gaiefsky
authors.forename: Eric
authors.initials: E
authors.lastname: Miller
mesh_terms: D015526:AIDS Dementia Complex / Q000175:diagnosis* / Q000503:physiopathology; D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001479:Basal Ganglia / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D018791:CD4 Lymphocyte Count; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007294:Inositol / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009483:Neuropsychological Tests; D019562:Viral Load / Q000145:classification
chemical_list: D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline