Reduced hippocampal glutamate in Alzheimer disease

Altered neurometabolic profiles have been detected in Alzheimer disease (AD) using 1H magnetic resonance spectroscopy (MRS), but no definitive biomarker of mild cognitive impairment (MCI) or AD has been established. This study used MRS to compare hippocampal metabolite levels between normal elderly controls (NEC) and subjects with MCI and AD. Short echo-time (TE = 46 ms) 1H spectra were acquired at 4 T from the right hippocampus of 23 subjects with AD, 12 subjects with MCI and 15 NEC. Absolute metabolite levels and metabolite ratios were compared between groups using a multivariate analysis of covariance (covariates: age, sex) followed by post hoc Tukey's test (p < 0.05 significant). Subjects with AD had decreased glutamate (Glu) as well as decreased Glu/creatine (Cr), Glu/myo-inositol (mI), Glu/N-acetylaspartate (NAA), and NAA/Cr ratios compared to NEC. Subjects with AD also had decreased Glu/mI ratio compared to MCI. There were no differences between subjects with MCI and NEC. Therefore, in addition to NAA/Cr, decreased hippocampal Glu may be an indicator of AD.