title: A lipid storage-like disorder contributes to cognitive decline in HIV-infected subjects.
abstract: OBJECTIVE
  In this multicenter cohort study, we sought to identify prognostic and associative metabolic indicators for HIV-associated neurocognitive disorders (HAND).
  
  
  METHODS
  A quantitative lipidomic analysis was conducted on 524 longitudinal CSF samples collected from 7 different performance sites across the mainland United States, Hawaii, and Puerto Rico. Subjects included HIV-infected individuals with longitudinal clinical and cognitive testing data and cognitively normal HIV-negative healthy controls.
  
  
  RESULTS
  At baseline, HIV+ subjects could be differentiated from HIV- controls by reductions in a single ceramide species and increases in multiple forms of cholesterol. Perturbations in cholesterol metabolism and ceramide were influenced by combined antiretroviral therapy (cART) use. There were no cross-sectional baseline differences in any lipid metabolite when HIV+ subjects were grouped according to cognitive status. However, a single sphingolipid metabolite and reduced levels of esterified cholesterols were prognostic indicators of incident cognitive decline. Longitudinal patterns of these disturbances in sphingolipid and sterol metabolism suggest that a progressive disorder of lipid metabolism that is similar to disorders of lipid storage may contribute to the pathogenesis of HAND.
  
  
  CONCLUSIONS
  These findings suggest that HIV infection and cART are independently associated with a CNS metabolic disturbance, identify surrogate markers that are prognostic for cognitive decline, and implicate a lipid storage-like disorder in the progression of HAND.
authors.affiliation: From the Department of Neurology, Division of Neuroimmunology and Neurological Infections (V.V.R.B., N.S., J.C.M., C.P., P.C., N.J.H.), and the Department of Psychiatry (N.J.H.), The Johns Hopkins University, School of Medicine, Baltimore, MD; the Department of Health Sciences Research (M.M.M.), Division of Epidemiology, The Mayo Clinic, Rochester, MN; HIV Neurobehavioral Research Program and Department of Psychiatry (I.G., S.L.), School of Medicine, University of California, San Diego, La Jolla; the Department of Psychiatry (L.C., S.M.), University of Hawaii, John A. Burns School of Medicine, Honolulu; and the Department of Neurology (V.W.), Specialized Neurosciences Research Program, University of Puerto Rico Medical Sciences Campus, San Juan.
authors.forename: Veera Venkata Ratnam
authors.initials: VV
authors.lastname: Bandaru
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Mielke
authors.forename: Ned
authors.initials: N
authors.lastname: Sacktor
authors.forename: Justin C
authors.initials: JC
authors.lastname: McArthur
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
authors.forename: Scott
authors.initials: S
authors.lastname: Letendre
authors.forename: Linda
authors.initials: L
authors.lastname: Chang
authors.forename: Valerie
authors.initials: V
authors.lastname: Wojna
authors.forename: Carlos
authors.initials: C
authors.lastname: Pardo
authors.forename: Peter
authors.initials: P
authors.lastname: Calabresi
authors.forename: Sody
authors.initials: S
authors.lastname: Munsaka
authors.forename: Norman J
authors.initials: NJ
authors.lastname: Haughey
mesh_terms: D015526:AIDS Dementia Complex / Q000134:cerebrospinal fluid* / Q000209:etiology / Q000503:physiopathology; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002518:Ceramides / Q000134:cerebrospinal fluid; D002784:Cholesterol / Q000134:cerebrospinal fluid; D005260:Female; D015658:HIV Infections / Q000134:cerebrospinal fluid* / Q000150:complications / Q000188:drug therapy; D006801:Humans; D052439:Lipid Metabolism Disorders / Q000134:cerebrospinal fluid* / Q000150:complications / Q000209:etiology; D008137:Longitudinal Studies; D008297:Male; D011237:Predictive Value of Tests; D013107:Sphingolipids / Q000134:cerebrospinal fluid
chemical_list: D015415:Biomarkers; D002518:Ceramides; D013107:Sphingolipids; D002784:Cholesterol
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