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N-acetylcysteine (NAC) did not improve executive function in vascular mild cognitive impairment (vMCI) overall. However, specific patient subgroups, identified by clinical factors, showed significant cognitive benefits from NAC treatment.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Gerontology

Background:

  • Oxidative stress (OS) is implicated in vascular mild cognitive impairment (vMCI).
  • N-acetylcysteine (NAC), an antioxidant, was investigated for its potential to mitigate cognitive decline in vMCI.
  • A prior randomized clinical trial showed no significant overall effect of NAC on executive function in vMCI patients.

Purpose of the Study:

  • To identify clinical predictors of response to N-acetylcysteine (NAC) in patients with vascular mild cognitive impairment (vMCI).
  • To explore heterogeneity in treatment effects of NAC on executive function in vMCI.
  • To inform personalized therapeutic strategies for vMCI targeting oxidative stress.

Main Methods:

  • A 24-week randomized clinical trial involving vMCI patients.
  • Baseline clinical variables were assessed for their impact on executive function changes with NAC versus placebo.
  • Multivariate regression and quartile-based analysis were used to identify predictors and stratify treatment effects.

Main Results:

  • Younger age, higher BMI, non-APOE4 status, lower apathy scores, elevated homocysteine, and ACE inhibitor use predicted better executive function improvement with NAC.
  • Treatment effects varied significantly across quartiles of predicted response (p<0.001).
  • Response rates in the highest quartile of predicted benefit reached 100%.

Conclusions:

  • Significant variability exists in NAC response among vMCI patients.
  • Certain subgroups demonstrate more substantial benefits from NAC, suggesting potential for personalized treatment.
  • These findings underscore the need for tailored approaches to managing oxidative stress in vMCI.