Decreased Glutamate Levels in Patients with Amnestic Mild Cognitive Impairment: An sLASER Proton MR Spectroscopy and PiB-PET Study

BACKGROUND AND PURPOSE: Glutamate levels may be informative about the declining neuronal health in the central nervous system. We used an advanced proton MR spectroscopy (¹H-MRS) protocol composed of semi-localization by adiabatic selective refocusing (sLASER) localization and FAST(EST)MAP shimming for detection of alterations in brain glutamate concentrations in patients with amnestic mild cognitive impairment. METHODS: Participants with amnestic mild cognitive impairment (n = 14; median age = 80) and age- and sex-matched clinically normal controls (n = 32; median age = 79) from the population-based Mayo Clinic Study of Aging were recruited prospectively to the 3T single-voxel ¹H-MRS study that examined metabolite changes in the posterior cingulate gyri. To be included, controls had to have low β-amyloid load on [¹¹C] Pittsburgh Compound B (PiB)-PET (standard uptake value ratio; SUVr < 1.42) and patients with amnestic mild cognitive impairment had to have high β-amyloid load (SUVr ≥ 1.42). RESULTS: Glutamate concentration and the glutamate/myo-inositol ratio were lower in patients with amnestic mild cognitive impairment than clinically normal controls (P <.05). Higher global cortical PiB-PET SUVr correlated with lower glutamate/myo-inositol (r = –.3, P =.04). CONCLUSIONS: The advanced sLASER with FAST(EST)MAP shimming is a promising protocol for identifying glutamate alterations. Advanced ¹H-MRS protocols may add to the understanding of early Alzheimer's disease pathophysiology through detection of glutamate concentration in posterior cingulate gyri of individuals with amnestic mild cognitive impairment.