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

**Authors:** Geraldine Rodríguez-Nieto, David F. Alvarez-Anacona, Mark Mikkelsen, Hong Li, Stephan P. Swinnen

PMC · DOI: 10.3389/fnagi.2026.1729015 · 2026-02-27

## TL;DR

This study explores how glutathione levels in the brain relate to cognitive performance and effort in young and older adults.

## Contribution

The study reveals age- and region-dependent relationships between glutathione and cognition, including cognitive endurance and brain chemistry.

## Key findings

- Glutathione in the IPL showed opposite relationships with memory tasks in young and older adults.
- Glutathione levels in both brain regions changed with sustained cognitive effort, depending on age and region.
- Glutathione modulation was linked to better cognitive performance in young adults and to GABA levels in a region- and age-dependent manner.

## Abstract

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.

## Linked entities

- **Chemicals:** glutathione (PubChem CID 124886), GABA+ (PubChem CID 119)

## Full-text entities

- **Chemicals:** GABA (MESH:D005680), GSH (MESH:D005978)

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12982376/full.md

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Source: https://tomesphere.com/paper/PMC12982376