A new study suggests that diminishing levels of GABA — the primary inhibitory neurotransmitter in the brain — may play a role in cognitive decline as we get older.
The research, published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, shows an association between higher concentrations of GABA (gamma-aminobutyric acid) in the frontal lobe, a brain region important for complex cognitive functioning, and high performance on a cognitive test in healthy older adults.
The study was led by Professor Ronald Cohen, Director for the Center on Cognitive Aging at the University of Florida (UF), and McKnight Brain Institute. The findings help researchers understand the potential role of age-related GABA decline in cognitive problems and suggest that lower levels of frontal GABA concentrations may help predict neurodegenerative disease.
“These results are an important step towards personalized approaches to age-related cognitive interventions,” said first author Dr. Eric Porges of the University of Florida department of clinical and health psychology in the College of Public Health and Health Professions, and a member of UF’s Center for Cognitive Aging and McKnight Brain Institute.
The cause of the relationship is still unknown, and the cognitive test used in the study is unable to distinguish which specific cognitive domains — such as attention or memory — might be affected by declining GABA concentrations. However, the relationship suggests a very promising target for new treatments.
“Interventions that increase GABA levels (such as exercise) could potentially offset these changes, and this paper opens up a pathway for investigating this exciting possibility,” said Dr. Cameron Carter, editor of the journal.
For the study, 94 healthy older adults (average age of 73 years) completed the Montreal Cognitive Assessment (MoCA), which measures several domains of cognition. The researchers also measured GABA concentrations in the frontal and posterior cortices of each participant to target regions that are important for high level cognitive functioning.
The analysis supports previous research showing that GABA levels may decrease in adulthood and that GABA concentrations continue to diminish in both regions into advanced age. The research also shows a link between reduced GABA concentrations in the frontal lobe and poor test scores. This association remained even after adjusting for age-related changes in cognitive function and tissue atrophy.
“To find that, independent of age and tissue atrophy, GABA levels predict individual differences in cognitive outcome is a provocative finding that may provide insight into physiological mechanisms of age-related cognitive decline,” said Porges.
No link was found between GABA concentrations and the MoCA score in the posterior region, suggesting that the effect on cognition is specific to reductions in the frontal lobe rather than brain-wide changes in GABA concentrations.