Factor analysis of proton MR spectroscopic imaging data in HIV infection: metabolite-derived factors help identify infection and dementia.
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.
Mohamed
Mona A
MA
Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, 1550 Orleans St, 492 CRB II, Baltimore, MD 21231, USA.
Lentz
Margaret R
MR
Lee
Vallent
V
Halpern
Elkan F
EF
Sacktor
Ned
N
Selnes
Ola
O
Barker
Peter B
PB
Pomper
Martin G
MG
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
D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline