The role of glutathione in cognition, cognitive effort, and cognitive endurance in young and older adults

Glutathione (GSH) is an abundant antioxidant that protects against endogenous and exogenous toxic agents. The evidence over the relationship between GSH and cognitive integrity during aging is still scarce. In this study we investigated the relationship between GSH and cognitive integrity, cognitive effort and sustained cognitive effort. Second, we explored whether GSH modulation is related to other physiological properties such as blood oxygenation (BOLD response) and to brain excitability (measured by GABA+ and Glx levels). We measured GSH levels through magnetic resonance spectroscopy (HERMES) at baseline and during cognitive task performance in 40 young (18-35 years; 26 female) and 40 older (60-85 years; 21 female) adults in two higher-order processing areas in the brain: the inferior frontal and the inferior parietal cortices (IFC and IPL). GSH in IPL related in opposite directions to distinct memory tasks in young and older adults. GSH levels in both regions showed a modulation as a result of sustained cognitive performance; the direction of this modulation was age- and region-dependent. Furthermore, GSH modulation positively related to cognitive performance in young adults. Finally, GSH showed a relationship with GABA that was region, age and state dependent. These results highlight the heterogeneity of GSH physiology, while its relation with cognition is dependent on age and brain region.