Objective:We aimed to study the relationship between glutathione (GSH), a key molecule of the anti-oxidant defense system in the blood, and glutathione reductase (GR), which reduces oxidized GSSG to GSH and maintains redox balance, with the prevalence of Alzheimer’s dementia and cognitive decline.Methods:20 with normal cognition and 20 with Alzheimer's dementia who completed the 3rd f/u clinical evaluation over 6 years were selected by matching age and gender. Plasma glutathione (GSH) and glutathione reductase (GR) concentrations were independent variables. Clinical diagnosis and neurocognitive test scores were used as dependent variables indicating cognitive status.Results:The higher the GR, the greater the possibility of normal cognition rather than Alzheimer's dementia. Also, the higher the GR, the higher the neurocognitive score. However, this association was not significant in GSH in any way. After 6 years, the conversion rate from normal cognition to cognitive impairment was significantly higher in the lower 50th percentile of the GR group than in the upper 50th percentile.Conclusion:According to the result of this study, the higher the GR, the lower the prevalence of Alzheimer's dementia and incidence of cognitive impairment, and the higher the cognitive outcome. Therefore, GR can be regarded as a protective biomarker for Alzheimer’s dementia and cognitive decline.