title: Cerebrospinal fluid metabolomics implicate bioenergetic adaptation as a neural mechanism regulating shifts in cognitive states of HIV-infected patients.
abstract: OBJECTIVE
  To identify prognostic surrogate markers for change in cognitive states of HIV-infected patients.
  
  
  METHODS
  Longitudinal cerebrospinal fluid (CSF) samples were collected from 98 HIV-infected patients identified by temporal change in cognitive states classified as normal, stably impaired, improving and worsening.
  
  
  METHODS
  The metabolic composition of CSF was analysed using H nuclear magnetic resonance (H NMR) spectroscopy that focused on energy metabolites. Metabolic biomarkers for cognitive states were identified using multivariate partial least squares regression modelling of the acquired spectra, combined with nonparametric analyses of metabolites with clinical features.
  
  
  RESULTS
  Multivariate modelling and cross-validated recursive partitioning identified several energy metabolites that, when combined with clinical variables, classified patients based on change in neurocognitive states. Prognostic identification for worsening was achieved with four features that included no change in a detectable plasma viral load, elevated citrate and acetate; decreased creatine, to produce a model with a predictive accuracy of 92%, sensitivity of 88% and 96% specificity. Prognosis for improvement contained seven features that included first visit age less than 47 years, new or continued use of antiretrovirals, elevated glutamine and glucose; decreased myo-inositol, β-glucose and creatinine to generate a model with a predictive accuracy of 92%, sensitivity of 100% and specificity of 84%.
  
  
  CONCLUSIONS
  These CSF metabolic results suggest that worsening cognitive status in HIV-infected patients is associated with increased aerobic glycolysis, and improvements in cognitive status are associated with a shift to anaerobic glycolysis. Dietary, lifestyle and pharmacologic interventions that promote anaerobic glycolysis could protect the brain in setting of HIV infection with combined antiretroviral therapy.
authors.affiliation: aDepartment of Pharmacology, University of Oxford, Oxford, UK bDepartment of Neurology cPsychiatry, Johns Hopkins University, Baltimore, Maryland dHIV Neurobehavioral Research Program and Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla, California eDivision of Epidemiology, Department of Health Sciences Research and Department of Neurology College of Medicine, Mayo Clinic, Rochester, Minnesota, USA fDepartment of Chemistry, University of Oxford, UK.
authors.forename: Alex M
authors.initials: AM
authors.lastname: Dickens
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Anthony
authors.forename: Reena
authors.initials: R
authors.lastname: Deutsch
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Mielke
authors.forename: Timothy D W
authors.initials: TD
authors.lastname: Claridge
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
authors.forename: Donald
authors.initials: D
authors.lastname: Franklin
authors.forename: Debra
authors.initials: D
authors.lastname: Rosario
authors.forename: Thomas
authors.initials: T
authors.lastname: Marcotte
authors.forename: Scott
authors.initials: S
authors.lastname: Letendre
authors.forename: Justin C
authors.initials: JC
authors.lastname: McArthur
authors.forename: Norman J
authors.initials: NJ
authors.lastname: Haughey
mesh_terms: D015526:AIDS Dementia Complex / Q000175:diagnosis* / Q000473:pathology*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D004734:Energy Metabolism; D006019:Glycolysis; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008137:Longitudinal Studies; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome; D011379:Prognosis
chemical_list: D015415:Biomarkers