Alzheimer's Research & Therapy · Apr 27, 2026

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

By Gallagher D, Kang Y, Herrmann N et al.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: N-acetylcysteine supplementation did not provide additional cognitive benefits beyond that of cardiac rehabilitation alone among patients with vascular mild cognitive impairment. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov on August 31, 2017 (NCT03306979).

doi.org/10.1186/s13195-026-02062-z Open access PubMed 42045982 Interventions