GABA levels decline with age: A longitudinal study

Abstract

Abstract One factor that might contribute to functional deterioration in healthy older adults is a decline in the brain’s major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). Previous studies have reported mixed results regarding whether GABA declines in healthy aging. These previous studies were cross-sectional and therefore cannot provide insight into GABA changes over time within aging individuals. Furthermore, aging is associated with gray and white matter atrophy that may confound age-related differences in GABA. In the present study, we utilized a repeated-measures, longitudinal design and MR spectroscopy to measure GABA levels in bilateral auditory, sensorimotor, and ventrovisual voxels of interest (VOI) in 30 healthy older adults at two time points a few years apart. Furthermore, we applied two of the most common tissue correction strategies to control for the effects of tissue composition on GABA estimates. Results from mixed-effects models showed that longitudinal change in age is a significant predictor of tissue-corrected longitudinal change in GABA levels: as age increases, GABA declines. In contrast, there was no cross-sectional effect of age on GABA in our sample (e.g., the oldest old did not have lower GABA levels than the youngest old). In conclusion, results from this study provide support for within-person, age-related declines in GABA over time, even after controlling for tissue composition.