Frontal Gamma-Aminobutyric Acid Concentrations Are Associated With Cognitive Performance in Older Adults

Abstract

Background: Gamma-aminobutyric acid (GABA), the brain's principal inhibitory neurotransmitter, has been associated with perceptual and attentional functioning. Recent application of magnetic resonance spectroscopy (MRS) provides in vivo evidence for decreasing GABA concentrations during adulthood. It is unclear, however, how age-related decrements in cerebral GABA concentrations contribute to cognitive decline, or whether previously reported declines in cerebral GABA concentrations persist during healthy aging. We hypothesized that participants with higher GABA concentrations in the frontal cortex would exhibit superior cognitive function and that previously reported age-related decreases in cortical GABA concentrations continue into old age.

Methods: We measured GABA concentrations in frontal and posterior midline cerebral regions using a Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) ¹H-MRS approach in 94 older adults without history or clinical evidence of mild cognitive impairment or dementia (mean age, 73 years). We administered the Montreal Cognitive Assessment to assess cognitive functioning.

Results: Greater frontal GABA concentrations were associated with superior cognitive performance. This relation remained significant after controlling for age, years of education, and brain atrophy. GABA concentrations in both frontal and posterior regions decreased as a function of age.

Conclusions: These novel findings from a large, healthy, older population indicate that cognitive function is sensitive to cerebral GABA concentrations in the frontal cortex, and GABA concentration in frontal and posterior regions continue to decline in later age. These effects suggest that proton MRS may provide a clinically useful method for the assessment of normal and abnormal age-related cognitive changes and the associated physiological contributors.

Keywords: Aging; Cognition; GABA; MEGA-PRESS; MRS; γ-Aminobutyric.

Figure 1

(A) Voxel locations in the frontal and posterior regions of the brain. The gray box represents the location of the 3 × 3 × 3 cm voxel collected using Mescher-Garwood point-resolved spectroscopy. (B) Edited spectra from the frontal and posterior voxels for all subjects. Gamma-aminobutyric acid (GABA) peak is at 3.02 ppm. (C) Representative Gannet GABA model fit. (D) Stacked dot plot demonstrating greater GABA concentrations in the posterior voxel. I.U., institutional unit.

Figure 2

Confidence intervals are 95% for the regression line. (A) Plot demonstrating greater participant age associated with lower performance on the Montreal Cognitive Assessment (MoCA). (B) Plot demonstrating the age-related decrease in frontal gamma-aminobutyric acid (GABA) concentrations. (C) Plot demonstrating the age-related decrease in posterior GABA concentrations. (D) Plot demonstrating the relation between frontal GABA concentrations and MoCA scores. The relation remains significant when the two highest GABA data points are removed. CSF, cerebrospinal fluid.