Early rise of glutamate-glutamine levels in mild cognitive impairment: Evidence for emerging excitotoxicity

Background: Use proton magnetic resonance spectroscopy (1H-MRS) non invasive technique to assess the modifications of glutamate-glutamine (Glx) and gammaaminobutyric acid (GABA) brain levels in patients reporting a cognitive complain METHODS: Posterior cingular cortex 1H-MRS spectra of 46 patients (19 male, 27 female) aged 57 to 87 years (mean : 73.32 ± 7.33 years) with a cognitive complaint were examined with a MEGA PRESS sequence at 3T, and compounds Glutamateglutamine (Glx), GABA, Creatine (Cr) and NAA were measured. From this data the metabolite ratios Glx/Cr, GABA/Cr and NAA/Cr were calculated. In addition, all patient performed the Mini Mental State Evaluation (MMSE) and 2 groups were realized with the clinical threshold of 24.

Results: 16 patients with MMSE 〈 24 and 30 patients with MMSE 〉 24. Significant increase of Glx/Cr in PCC of patients with MMSE 〈 24 compared to patients with MMSE 〉 24. Moreover, GABA/Cr ratio exhibited a trend for a decrease in PCC between the two groups, while they showed a significant decrease NAA/Cr ratio.

Conclusion: Our results concerning Glx are in agreement with a physiopathological hypothesis involving a biphasic variation of glutamate levels associated with excitotoxicity, correlated with the clinical evolution of the disease. These observations suggest that MRS assessment of glutamate levels could be helpful for both diagnosis and classification of cognitive impairment in stage.