Skip to main content
Evidence-Based Supplement Research
Evidence-Based Supplement Research
Pillser
Search
Sign UpLog In

Frontal white matter hyperintensity burden predicts cognitive response to N-acetylcysteine and exercise in vascular mild cognitive impairment.

  • 2026-05
  • Neurobiology of aging 161
    • Ethan Mah
    • Damien Gallagher
    • Fuqiang Gao
    • Joel Ramirez
    • Jennifer S Rabin
    • Kate Survilla
    • Danielle Vieira
    • Jinghan Jenny Chen
    • Yejin Kang
    • Ana Andreazza
    • Nathan Herrmann
    • Alex Kiss
    • Susan Marzolini
    • Paul Oh
    • Walter Swardfager
    • Sandra E Black
    • Krista L Lanctôt

Study Design

Type
Randomized Controlled Trial (RCT)
Population
58 individuals with vaMCI
Methods
randomized to NAC or placebo; both groups received exercise therapy; WMH volumes measured from baseline MRI; linear mixed models
Duration
6 months
Vascular mild cognitive impairment (vaMCI) is a prodromal stage of dementia defined by cognitive deficits due to cerebrovascular disease. Increased white matter hyperintensity (WMH) volume has been associated with reduced executive function (EF). We explored whether lower baseline frontal and global WMH volume predicted an improvement in EF in vaMCI participants treated with N-acetylcysteine (NAC) and exercise as compared to placebo and exercise. Fifty-eight individuals with vaMCI received exercise therapy and were randomized to NAC or placebo. EF was assessed using the Trail Making Test Part B (TMT-B), Digit Symbol-Coding Test (DSCT), and a test of phonemic fluency, at baseline, 3 months, and 6 months. WMH volumes were measured from baseline magnetic resonance imaging scans. Linear mixed models were used. All participants improved on TMT-B (β = -0.185, SE = 0.046, p < 0.001) and phonemic fluency (β = 4.440, SE = 0.911, p < 0.001) over 6 months. A significant three-way interaction between baseline frontal WMH volume, treatment group, and timepoint predicted TMT-B performance at 3 months (β = 0.160, SE = 0.076, p = 0.039), but not at 6 months. No significant interactions were found for DSCT or phonemic fluency. Global WMH did not predict treatment response. Participants demonstrated improvement in EF regardless of treatment group and WMH volume. Lower frontal WMH volume predicted a greater improvement in TMT-B performance at 3 months in those treated with NAC versus placebo. These findings underscore the importance of considering participant heterogeneity in trials for vaMCI.

Research Insights

Back to top