Age-related glutamate and glutamine concentration changes in normal human brain: 1H MR spectroscopy study at 4 T

Abstract

Proton magnetic resonance spectroscopy was performed at 4 T to determine effects of age, region and gender on glutamate and glutamine in the normal human brain. Furthermore, glutamate and glutamine alterations with age were tested for correlations with other cerebral metabolites. Two 8 cm3 volumes were selected in corona radiata and mesial motor cortex in normal subjects (N = 24) between 24 and 68 years old. Older subjects had lower glutamate concentration in the motor cortex compared to younger subjects (p < 0.001). In corona radiata, older subjects demonstrated a trend in higher glutamine compared to younger subjects (p = 0.05). Glutamate in the motor cortex was positively correlated with glutamine, N-acetyl aspartate and creatine. Reduced glutamate and N-acetyl aspartate in the motor cortex is consistent with neuronal loss/shrinkage with age. In conclusion, different patterns in association with normal aging in these brain regions were detected in this study.

Fig. 1

Representative T₁-weighted MR image used for the placement of the two regions of interest (8 mL)-mesial motor cortex and corona radiata. (A) Simulated ¹H MR spectrum used as a prior knowledge for fitting experimental spectra. (B) Top-representative experimental ¹H MR spectrum from mesial motor cortex (thin line) and computed baseline (thick line). Bottom, baseline corrected experimental spectrum from the same region (thin line) with superimposed fitted spectrum (thick line). (C) Top-representative experimental ¹H MR spectrum from corona radiata (thin line) and computed baseline (thick line). Bottom, baseline corrected experimental spectrum from the corona radiata (thin line) with superimposed fitted spectrum (thick line).

Fig. 2

Concentrations of glutamate (A) and glutamine (B) as a function of age in corona radiata and mesial motor cortex areas. (A) Glutamate concentration as a function of age. (B) Glutamine concentration as a function of age. (C) The intensity ratio Glu/Gln is calculated directly from the ratio of the respective metabolites areas in the MR spectrum and is shown here as a function of age.

Fig. 3

Correlations between Glu and other metabolites in the mesial motor cortex area (A) Glu vs. Gln (r = 0.52, p < 0.01), (B) Glu vs. NAA (r = 0.86, p < 0.001), (C) Glu vs. Cr (r = 0.78, p < 0.001).