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

Detcheverry, F. E.; Senthil, S.; Motue, W. L.; Hosein, C.; Arnaoutelis, R.; Araujo, D.; Fetco, D.; Assemlal, H.-E.; Antel, S.; Arnold, D. L.; Near, J.; Schipper, H. M.; Badhwar, A.; Narayanan, S.

2024-09-26 neurology
10.1101/2024.09.24.24313962 medRxiv
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INTRODUCTIONOxidative stress may contribute to brain injury in Alzheimer disease (AD) continuum. The antioxidant glutathione (GSH) can be assessed with magnetic resonance spectroscopy (MRS). Since the relationship between GSH and vascular-brain injury is unknown in the AD continuum, we address this gap in mild cognitive impairment (MCI). METHODS3T 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. RESULTSSignificant associations were reported in FWM between GSH/total creatine (tCr) and tNAA/tCr, and between GSH and both WMH and NBV. tNAA, GSH/tCr, and tNAA/tCr were higher in PCC than FWM. DISCUSSIONOur results suggest that oxidative stress contributes to vascular-brain injury in MCI.

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