Oxidative stress predicts cognitive decline with aging in healthy adults: an observational study

• Type of Material: Article
• Authors: Ihab M. Hajjar, Emory University; Salim S. Hayek, Emory University; Felicia Goldstein, Emory University; Greg Martin, Emory University; Dean P Jones, Emory University; Arshed Ali Quyyumi, Emory University
• Language: English
• Date: 2018-01-16
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s12974-017-1026-z
• Title of Journal or Parent Work: Journal of Neuroinflammation
• ISSN: 1742-2094
• Volume: 15
• Issue: 1
• Start Page: 17
• End Page: 17
• Grant/Funding Information: Dr. Jones is supported by NIH grants P20HL113451, ES023485, ES025632, ES026560, HD075784, P30ES019776, AG038746, HL095479, EY022618, HL086773, CA188038, MMH107205, HHSN272201200031C, Henry M. Jackson Foundation HT9404-13-0030, and a California Breast Cancer Research Program Grant.; The Predictive Health Institute is supported by Emory University and the National Center for Advancing Translational Sciences of the National Institutes of Health (UL1 TR000454).; This analysis was funded by grants R01AG042127 to Ihab Hajjar.; Dr. Quyyumi is supported by NIH grants 5P01HL101398-02, 1P20HL113451-01, 1R56HL126558-01, 1RF1AG051633-01, R01 NS064162-01, R01 HL89650-01, HL095479-01, 1U10HL110302-01, 1DP3DK094346-01, 2P01HL086773, and American Heart Association Grant no. 0000031288.
• Keywords: Cognition; Neurosciences; BRAIN; NEURODEGENERATION; Cysteine; Life Sciences & Biomedicine; Oxidation; Neurosciences & Neurology; GSH TRANSPORTER; ALZHEIMERS-DISEASE; Inflammation; PARKINSONS-DISEASE; Science & Technology; PROTEIN OXIDATION; GLUTATHIONE LEVELS; Glutathione; Immunology; ASTROGLIAL CELLS; GAMMA-GLUTAMYL-TRANSPEPTIDASE; CULTURED ASTROCYTES; Aging
• Research Categories: Gerontology; Health Sciences, Immunology; Biology, Neuroscience

Abstract

Background: Redox signaling, which can be assessed by circulating aminothiols, reflects oxidative stress (OS) status and has been linked to clinical cardiovascular disease and its risk factors. These, in turn, are related to executive function decline. OS may precede the pro-inflammatory state seen in vascular disease. The objective of this study is to investigate the association between aminothiol markers of OS and inflammation in cognitive decline, especially in the executive cognitive domain which is highly susceptible to cardiovascular risk factors and is an important predictor of cognitive disability. Methods: The study design is that of a longitudinal cohort study within the setting of a large academic institution with participants being university employees (n=511), mean age 49years, 68% women, and 23% African-American. These participants were followed for four consecutive years with a yearly cognitive assessment conducted using computerized versions of 15 cognitive tests. Peripheral cystine, glutathione, their disulfide derivatives, and C-reactive protein (CRP) were measured. Results: Lower levels of glutathione at baseline was associated with a decline in the executive domain over 4years (covariate-adjusted relative risk (RR) for glutathione = 1.70 (95% CI=1.02-2.85), p=0.04). Furthermore, a longitudinal decline in glutathione level was associated with a faster decline in the executive domain (p=0.03). None of the other OS markers or CRP were linked to cognitive decline over 4years. Conclusion: Increased OS reflected by decreased glutathione was associated with a decline in executive function in a healthy population. In contrast, inflammation was not linked to cognitive decline. OS may be an earlier biomarker that precedes the inflammatory phase of executive decline with aging.