title: Factor analysis of proton MR spectroscopic imaging data in HIV infection: metabolite-derived factors help identify infection and dementia.
abstract: OBJECTIVE
  To develop a relevant pathophysiologic model of human immunodeficiency virus (HIV)-associated dementia by studying regional variations in metabolite levels measured with magnetic resonance (MR) spectroscopic imaging and their relationship to immunologic measures and cognitive dysfunction.
  
  
  METHODS
  This was a HIPAA-compliant, institutional review board-approved study involving written informed consent. Distributions of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) concentrations in 94 subjects (20 seronegative controls and 74 HIV-positive subjects; 34 of the HIV-positive subjects having HIV-associated dementia; 63 men, 31 women; mean age, 40 years) were determined with proton (hydrogen 1 [(1)H]) MR spectroscopic imaging. HIV-positive subjects underwent neuropsychological testing and blood and cerebrospinal fluid (CSF) analysis. Factor analysis was utilized to determine associations between metabolites across regions. Analysis of variance and t tests were used to isolate differences between cohorts.
  
  
  RESULTS
  A "Cho factor" differentiated seronegative controls from HIV-infected cohorts, indicating elevated Cho levels across deep gray and white matter regions of HIV-positive individuals. An "NAA factor" differentiated those with dementia from those without and correlated best with psychomotor and executive function tests. A "Cr factor" indicated Cr elevations correlated with CSF monocyte chemoattractant protein-1 levels. NAA and Cr factor scores were strongly weighted to metabolite changes in white matter regions.
  
  
  CONCLUSIONS
  These results highlight the importance of white matter involvement in HIV-associated dementia and support the current pathogenesis model of glial cell proliferation in HIV infection, denoted by regional Cho elevations, and neuronal dysfunction and/or death, denoted by NAA decreases, associated with dementia. Factor analysis of MR spectroscopic imaging data is a useful method for determining regional metabolic variations in HIV infection and its neuropsychological correlates.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, 1550 Orleans St, 492 CRB II, Baltimore, MD 21231, USA.
authors.forename: Mona A
authors.initials: MA
authors.lastname: Mohamed
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Lentz
authors.forename: Vallent
authors.initials: V
authors.lastname: Lee
authors.forename: Elkan F
authors.initials: EF
authors.lastname: Halpern
authors.forename: Ned
authors.initials: N
authors.lastname: Sacktor
authors.forename: Ola
authors.initials: O
authors.lastname: Selnes
authors.forename: Peter B
authors.initials: PB
authors.lastname: Barker
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
mesh_terms: D015526:AIDS Dementia Complex / Q000378:metabolism*; D000328:Adult; D000704:Analysis of Variance; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D005163:Factor Analysis, Statistical; D005260:Female; D015658:HIV Infections / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009483:Neuropsychological Tests
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline