Objective: The aim of this study was to use single voxel Proton Nuclear Magnetic Resonance Spectroscopy (1H-NMRS) in vulnerable brain areas, such as hippocampus and cingulate gyrus, to distinguish subjects with Mild Cognitive Impairment (MCI) from those with mild probable AD (MPRAD) and normal, healthy, age, sex and education matched controls.
Design: This is a cross sectional study comparing three groups of subjects: MCI, MPRAD and Control. They were all scanned once at the University of Chicago, Dept of Radiology with the identical protocol by the PI, and three brain areas were identified for study: right hippocampus, left hippocampus and posterior cingulate gyrus. Data from the scan was collected at the time of the study and analyzed by either student's t test or repeated measures analysis of variance.
Materials and Methods: All subjects were recruited from the University of Chicago Memory Center or the Northwestern Alzheimer's Disease Center and were diagnosed by consensus after extensive neuropsychological testing and neurological exam. All NMRS scans were performed on a 3T GE whole body system with appropriate head coil. The scans took about 45 minutes. We acquired single voxel proton data in 3 regions of interest(ROI): right hippocampus, left hippocampus and posterior cingulate gyrus, after a obtaining a structural MRI. ROI's were determined by visual placement and voxel size was 2X2x1 cm. MRS data is expressed as ratios of NAA, (N-acetyl aspartate), CHO (Choline) and MI (myoinositol) to CR (creatine). We studied 8 MCI, 6 MPRAD and 17 Control subjects.
Results: Mean MMSE for the three groups were: 29.2 for Control, 28.5 for MCI and 22.8 for MPRAD. There was no significant difference between any of the groups for age, sex or education. Mean MMSE of the MPRAD group was significantly different from Control and MCI groups but the latter two did not differ from each other .We found a significant decrease (p<.003) of NAA/CR in the right hippocampus in subjects with MCI and MPRAD compared to Controls. Left hippocampal NAA/Cr ratios were also decreased in the MCI and MPRAD groups compared to Controls but were not as significant. CHO/CR ratios in both hippocampi were decreased in the MPRAD group but not the MCI group. No difference was found in the posterior cingulate gyrus for any metabolite in any of the groups.
Conclusion: Since NAA is considered a marker of neuronal loss or integrity, our findings suggest that the the right hippocampus may be affected quite early in the disease process, at the MCI stage, and needs to be evaluated along with the left hippocampus in future NMRS studies of AD. 1H-NMRS may be a useful adjunct to the structural MRI in the diagnostic work-up of patients with very mild cognitive impairments.
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