Purpose: The aim of the study was to determine if changes in the hippocampal glutamate and glutamine (GLX) levels in patients with mild cognitive impairment (MCI) can be detected non invasively using proton magnetic resonance spectroscopy (1H-MRS). The glutamate neurotransmitter system is well known to be altered in Alzheimer's disease (AD). However, less is known about changes of the glutamate system in MCI. Due to advances in magnetic resonance technology both glutamate and glutamine spectra can be measured in vivo with 1H-MRS. We now studied whether changes of the GLX components can be detected non invasively in subjects with MC
Methods and Materials: MCI was defined as: 1) a history (subjective or caregiver complaint) of impaired cognition, 2) an objective cognitive deficit, 3) in a patient with normal activities of daily living and 4) no signs of dementia. Operationally a Mini Mental State Examination (MMSE) score between 27 and 24 was required for inclusion in the MCI group. After informed consent 6 patients with MCI and 8 normal subjects were included in the study. 1H-MRS was performed at 1.5 Tesla clinical scanner (Magnetom Vision, Siemens, FRG) using a stimulated echo acquisition mode (STEAM)-sequence in the left hippocampus and the left parietal cortex (volume of interest 8 ml, TR = 3000 ms, TE = 20 ms) located on T2w axial images. Fully automated spectra analysis was performed using the LCModel program. Metabolite concentrations were normalized to the creatine (CR) signal and expressed in ratio
Results: Reduced ratios for both N-acetylaspartate (NAA) and GLX were found in hippocampus but not in parietal cortex in patients with MCI when compared with normal subjects. Statistical group comparisons (Student's t-test) were significant for NAA/CR (P<0.001) and GLX/CR (P<0.007). No significant changes were found for choline and myo-inositol measurements.
Conclusion: The glutamate system may play a crucial role in MCI and the early stages of AD. The finding of decreased GLX in MCI measured with 1H-MRS could be of great diagnostic value in detecting early stages of neurodegeneration. Furthermore, it potentially offers new aspects for therapeutic intervention and its monitoring.
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