Efficacy and safety of N-acetylcysteine in patients with mild cognitive impairment undergoing exercise-based cardiac rehabilitation program: a randomized controlled trial

Oxidative stress is implicated in the etiology of mild cognitive impairment. We hypothesized that oral supplementation with N-acetylcysteine, a precursor to the antioxidant glutathione, would improve cognitive outcomes among individuals with mild cognitive impairment. n this 24-week randomized, double-blind, placebo-controlled trial, participants enrolled in an exercise-based cardiac rehabilitation program with possible vascular mild cognitive impairment were randomized to receive either oral N-acetylcysteine (2400 mg/day) or placebo. Cognition was assessed using a neuropsychological battery, with a standardized executive function composite score as the primary outcome. Secondary outcomes included verbal memory, working memory, non-verbal memory, attention and global cognition. Data were analyzed using linear mixed-effects models, adjusting for relevant covariates. A total of 59 participants [mean (SD) age = 67.6 (7.7), male (%) = 69.5%, mean (SD) Montreal Cognitive Assessment = 22.5 (3.2)] were randomized. The executive function composite score improved over time (B = 0.31, 95% CI = [0.14, 0.48], p < 0.001), with no significant differences between N-acetylcysteine and placebo (B = -0.04, 95% CI = -0.28 to 0.20, p = 0.8) or in other cognitive domains. N-acetylcysteine was generally well-tolerated, with adverse events comparable between groups. N-acetylcysteine supplementation did not provide additional cognitive benefits beyond that of cardiac rehabilitation alone among patients with vascular mild cognitive impairment. This study was registered with ClinicalTrials.gov on August 31, 2017 (NCT03306979).