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MOVE-IT MRS: Linking glutathione and cognitive response: a pilot phase 2a study of N-acetylcysteine in vascular cognitive impairment, no dementia

This study is a part of the larger MOVE-IT TRIAL (hyperlink to the introduction page of MOVE-IT).

As an add-on study to the MOVE-IT trial, MOVE-IT MRS will use MRI, magnetic resonance spectroscopy (MRS) and positron emission tomography (PET) technology to study the effect of an antioxidant on central brain glutathione levels.

While the antioxidant defense molecule glutathione (GSH) serves as the primary antioxidant in the brain, GSH depletion plays an important role in oxidative stress-mediated neuronal death, leading to neurodegeneration and neurodegenerative disease. Recent research has found that brain GSH concentrations were lower in mild cognitive impairment and Alzheimer’s disease, but no studies have assessed the GSH concentration in patients with coronary artery disease (CAD) and early memory problems, or mild vascular cognitive impairment (VCI).

The MOVE-IT study explores whether the antioxidant supplement N-acetylcysteine (NAC) is a safe and effective therapy to improve cognition in mild VCI. Patients will be randomized to receive antioxidant NAC supplements or a placebo for 24 weeks while participating in a supervised exercise program.

For MOVE-IT MRS, 30 participants with mild VCI from the MOVE-IT trial will undergo MRI and MRS scans at the beginning and end of NAC/placebo supplementation to determine whether the antioxidant supplement increases central GSH levels in the brain. Thirty participants from the CAD control group who are matched by sex and age will also undergo MRI and MRS scans to compare baseline GSH levels. A PET scan of the brain will also be done on all 30 mild VCI patients to explore the relationships between amyloid-beta status, cognitive outcomes and blood biomarkers.

Our results will help answer the question of whether NAC, a safe and widely available health supplement, can influence GSH levels in the brain and delay the onset of dementia.