Plasma GSH levels and Alzheimer's disease. A prospective approach.: Results from the HELIAD study

Free Radic Biol Med. 2021 Jan:162:274-282. doi: 10.1016/j.freeradbiomed.2020.10.027. Epub 2020 Oct 21.


Background: Potential links between oxidative stress and the pathophysiology of Alzheimer's disease (AD) have been reported in the existing literature. Biological markers of oxidative stress, such as the reduced form of glutathione (GSH), may have a potential role as predictive biomarkers for AD development. The aim of the present study was to explore the longitudinal associations between plasma GSH and the risk of developing AD or cognitive decline, in a sample of community-dwelling, non-demented older adults.

Methods: Participants from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) were included in the present prospective study. The sample used in the analyses consisted of 391 non-demented individuals over the age of 64 (mean age = 73.85 years; SD = 5.06), with available baseline GSH measurements and longitudinal follow-up. Plasma GSH was treated both as a continuous variable and as tertiles in our analyses. Cox proportional hazards models were used to evaluate the hazard ratio (HR) for AD incidence as a function of baseline plasma GSH. Generalized estimating equations (GEE) models were deployed to explore the associations between baseline plasma GSH and the rate of change of performance scores on individual cognitive domains over time. Models were adjusted for age, years of education and sex. Supplementary exploratory models were also adjusted for mild cognitive impairment (MCI) at baseline, risk for malnutrition, physical activity and adherence to the Mediterranean dietary pattern.

Results: A total of 24 incident AD cases occurred during a mean (SD) of 2.99 (0.92) years of follow-up. Individuals in the highest GSH tertile group (highest baseline plasma GSH values) had a 70.1% lower risk for development of AD, compared to those in the lowest one [HR = 0.299 (0.093-0.959); p = 0.042], and also demonstrated a slower rate of decline of their executive functioning over time (5.2% of a standard deviation less decline in the executive composite score for each additional year of follow-up; p = 0.028). The test for trend was also significant suggesting a potential dose-response relationship.

Conclusion: In the present study, higher baseline plasma GSH levels were associated with a decreased risk of developing AD and with a better preservation of executive functioning longitudinally.

Keywords: Aging; Alzheimer's disease; Cognition; Dementia; Glutathione; Redox biomarkers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging
  • Alzheimer Disease* / epidemiology
  • Cognitive Dysfunction* / epidemiology
  • Diet
  • Glutathione
  • Humans
  • Longitudinal Studies
  • Prospective Studies


  • Glutathione