MRS demonstrates elevated brain glutathione in vascular mild cognitive impairment compared to cognitively normal coronary artery disease controls

INTRODUCTION: Oxidative stress (OS) is implicated in dementia. While elevated peripheral OS biomarkers were observed in vascular mild cognitive impairment (vMCI), the role of central antioxidants remains unclear. We assessed levels of the major brain antioxidant glutathione (GSH) in vMCI compared to cognitively normal coronary artery disease (CAD) controls (CN). METHODS: In vivo tissue-corrected GSH in the anterior cingulate cortex (ACC) and occipital cortex (OC) were quantified in persons with vMCI and CN using MEscher-GArwood Point RESolved magnetic resonance Spectroscopy. RESULTS: Among participants (vMCI, n = 22, age [mean ± SD] = 67.4 ± 7.3; CN, n = 21, age = 66.7 ± 7.8), ACC-GSH (i.u. ± SD) was higher in vMCI (4.42 ± 0.59) versus CN (3.72 ± 1.01) (Z = -2.5, p = .01), even after controlling for age and sex (B [SE] = 0.74 [0.26], p = .007). Increased ACC-GSH correlated with poorer executive function (EF) (B [SE] = -0.31 [0.14], p = .04). OC-GSH showed no effect. DISCUSSION: Higher ACC-GSH in vMCI may reflect a compensatory response to OS. ACC-GSH was negatively correlated with EF, suggesting a linkage between regional brain antioxidants and disease-relevant cognitive domains. HIGHLIGHTS: Brain GSH was measured in vascular MCI and matched controls using MEGA-PRESS. In contrast to GSH deficits in AD, anterior cingulate GSH was elevated in vMCI. Brain GSH was correlated with disease-relevant cognitive domains in vMCI. The GSH antioxidant system may be etiologically implicated in vMCI.