Is Higher Antioxidant Capacity an Important Determinant of Cognitive Performance? Editorial Highlight on “Brain Glutathione Levels Associate With Cognitive Performance in Older Adults” by Lee et al.

Glutathione is a major component of the cellular antioxidant system, providing a means of controlling redox homeostasis and affording protection against oxidative damage. Proton magnetic resonance spectroscopy (MRS) offers insights into brain metabolism by enabling the noninvasive quantification of metabolites. Previous studies have demonstrated that the neurotransmitters glutamate and GABA detected by MRS show activity-dependent concentration changes and correlate with cognitive performance. Yet how MRS detected antioxidant capacity, particularly glutathione levels, relates to cognition remains unclear. In this issue, Lee et al. report that higher cortical glutathione levels are associated with better cognitive outcomes in older adults. These findings might contribute to understanding whether glutathione levels index resilience or degeneration. However, observations reported across the literature remain inconsistent, and the observed discrepancies underscore the need for further research using harmonized MRS acquisitions, deeper metabolic and cognitive phenotyping, and longitudinal study designs to clarify the role of cortical glutathione in cognitive trajectories.