Brain Glutathione Levels Associate With Cognitive Performance in Older Adults

Glutathione (GSH), the brain's primary endogenous antioxidant, is integral to the cerebral antioxidant defense system and essential for maintaining redox homeostasis and neuronal health. Brain GSH levels naturally decrease with age, potentially contributing to cognitive vulnerability through diminished antioxidant capacity. Currently, the relationship between brain GSH and cognitive function in humans remains poorly understood. Using multiple quantum chemical shift imaging, we measured brain GSH levels in 206 cognitively unimpaired older adults (mean age 69.8 ± 3.9 years) and assessed cognitive performance across five core domains: working memory, episodic memory, visuospatial processing, executive function/attentional control, and processing speed. We hypothesized that higher GSH would be associated with better cognitive performance across all five domains, reflecting the putative role of antioxidant capacity in cognitive function. Using multiple regression with age, sex, years of education, and study site as covariates in the model, we found that higher regional brain GSH levels, including frontal and parietal regions, were associated with better working memory (p = 0.008), episodic memory (p = 0.040), and visuospatial processing (p = 0.001), but not with executive function/attentional control or processing speed. These findings highlight the critical neuroprotective role of GSH within the cerebral antioxidant defense system in supporting cognitive health in late adulthood.