Grant: Project Grant

Despite promising leads, to date clinical trials of medications to halt or reverse dementia have failed. Consequently, treatment interventions for dementia are now focusing on those with cognitive problems who are at high risk of progressing, to intervene before there is irreversible damage to the brain. Cognitive problems are common in patients with heart disease and those who experience cognitive difficulties are more likely to develop dementia. While exercise can help many people maintain cognition, many people do not achieve cognitive benefits. Our research has provided the first evidence that oxidative stress may limit the benefits of exercise on brain function and cognition. Recent research suggests that reducing oxidative damage in the brain may possibly be an effective way to prevent the brain changes that lead to the cognitive deficits and functional impairment in dementia. N-acetylcysteine (NAC), a widely available and safe supplement, has powerful antioxidant effects, which may be beneficial to boost cognition. This study will test whether the antioxidant supplement NAC is safe and effective to improve cognition in patients with heart disease who show early memory problems, known as vascular cognitive impairment-no dementia (VCIND). In the current study, patients will be randomized to NAC supplements or placebo orally for 24 weeks while participating in a supervised exercise program. Standardized neuropsychological testing will be used to compare cognitive performance between the placebo and NAC groups. We will use new techniques to accurately measure the amount of oxidative stress damage in blood and evaluate whether the treatment is more efficacious in individuals with certain brain characteristics on MRI scans. If positive, these results will be important for the design of a longer term trial to investigate whether NAC can delay the onset of dementia.