Investigating the oxidative stress–vascular brain injury axis in mild cognitive impairment of the Alzheimer type

Oxidative stress, an imbalance between production and neutralization of reactive oxygen species, can damage brain cells and contribute to cognitive decline in Alzheimer disease (AD) continuum. Levels of glutathione (GSH), the most prevalent endogenous brain antioxidant, can be assessed with magnetic resonance spectroscopy (MRS) and serves as a brain-oxidative stress index. Since the relationship between GSH and vascular-brain injury is unknown in the AD continuum, we address this gap in mild cognitive impairment (MCI) of the AD type. 3T MRI/MRS data were obtained from 31 MCI participants. GSH and total N-acetylaspartate (tNAA; neuroaxonal integrity marker) were measured in posterior cingulate cortex (PCC) and frontal white matter (FWM). Cerebrovascular injury was assessed using white matter hyperintensity (WMH) volume. Global and regional brain tissue integrity were assessed using normalized brain (NBV) and hippocampal volumes, respectively. Levels of tNAA, GSH/total creatine (tCr), and tNAA/tCr were higher in PCC than FWM. Significant associations were reported in FWM between GSH/tCr and tNAA/tCr, and between GSH and both WMH and NBV. Our results suggest that oxidative stress contributes to vascular-brain injury in MCI of the AD type.