Edited magnetic resonance spectroscopy detects an age-related decline in brain GABA levels

Abstract

Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain. Although measurements of GABA levels in vivo in the human brain using edited proton magnetic resonance spectroscopy ((1)H-MRS) have been established for some time, it is has not been established how regional GABA levels vary with age in the normal human brain. In this study, 49 healthy men and 51 healthy women aged between 20 and 76 years were recruited and J-difference edited spectra were recorded at 3T to determine the effect of age on GABA levels, and to investigate whether there are regional and gender differences in GABA in mesial frontal and parietal regions. Because the signal detected at 3.02 ppm using these experimental parameters is also expected to contain contributions from both macromolecules (MM) and homocarnosine, in this study the signal is labeled GABA+ rather than GABA. Significant negative correlations were observed between age and GABA+ in both regions studied (GABA+/Cr: frontal region, r=-0.68, p<0.001, parietal region, r=-0.54, p<0.001; GABA+/NAA: frontal region, r=-0.58, p<0.001, parietal region, r=-0.49, p<0.001). The decrease in GABA+ with age in the frontal region was more rapid in women than men. Evidence of a measureable decline in GABA is important in considering the neurochemical basis of the cognitive decline that is associated with normal aging.

Fig.1

The VOIs position in the frontal region (a) and parietal region (b) for spectroscopic measurement using a MEGA-PRESS sequence. The white box represents the location of the VOI (3 × 3 × 3 cm³) in the sagittal and axial images. (c) The 3D T1-weighted brain images (left) were segmented as gray matter (GM), white matter (WM), or cerebrospinal fluid (CSF) using the FAST (FMRIB’s automated segmentation tool) of the “FSL” software package (right) and the VOIs were re-created using the “Re-creation of VOI” Matlab tool.

Fig.2

The mean (plus/minus standard deviation) GABA-edited spectra from the MEGA-PRESS sequence for each decade in the frontal region and parietal region.

Fig.3

Age-related decreases in GABA+/Cr ratio in the frontal region (a) and parietal region (b) from all the subjects. (c) Age-related decreases in GABA+/Cr ratio in the men and women in the frontal region (men: r = -0.56, p < 0.001; women: r = -0.78, p < 0.001). P value of interaction in gender-by-age is 0.025.

Fig.4

Relationship between GM fraction and age in the frontal region (a) and parietal region (b) from all the subjects. Relationship between GABA+/Cr ratio and GM fraction in the frontal region (c) and parietal region (d) from all the subjects.