PROTON MRS OF PATS W/ AIDS DEMENTIA COMPLEX: MULTICENTER ACTG 301 DRUG EVAL

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This study concerns itself with patients suffering from the AIDS dementia complex who were enrolled in a double-blind, placebo-controlled study of memantine as a treatment for this disorder. The aim is to examine the pattern and extent of cerebral injury noninvasively using proton magnetic resonance spectroscopy (MRS). The University of PA is one of eleven centers involved in this combined treatment study and MRS research effort. The project uses the FDA-approved method of MRS referred to as PROBE, which is an automated method of acquiring and analyzing proton spectra. We select voxels (8 cc) from the basal ganglia (deep gray matter), the midline of the posterior parietal lobes (gray matter) and the mid-frontal centrum semiovale (white matter). Currently, twelve patients have undergone neuropsychological testing as well as the MRS protocol prior to drug/placebo treatment. The MRS protocol has been repeated in nine of these patients after sixteen weeks of therapy. The PROBE method only reports on the levels of three metabolites, giving the ratios of NAA, Cho, and mI to Cr. We are developing routines, fitting within the time domain, that will permit us to determine those areas of resonance which are attributable to all metabolites, especially the amino acids in macromolecule proteins. The study will likely reveal relationships between HIV-associated brain metabolic abnormalities, cellular injury and the neurobehavioral patterns of the AIDS dementia complex. This work should also affirm the suitability of proton MRS to studying, noninvasively and in vivo, the pathogenetic events in brains of patients infected with HIV. Finally, through such work we can gauge the effectiveness of novel CNS therapies.