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N-Acetylcysteine is associated with changes in functional connectivity in patients with Parkinson's disease.

  • 2026-03
  • Parkinsonism & related disorders 144
    • Daniel A Monti
    • George Zabrecky
    • Daniel Kremens
    • Tsao-Wei Liang
    • Nancy A Wintering
    • Faezeh Vedaei
    • Emily Navarreto
    • Monisha Gupta
    • Alicia Steinmetz
    • Anthony J Bazzan
    • Feroze Mohammed
    • Andrew B Newberg

Study Design

Type
Randomized Controlled Trial (RCT)
Population
44 patients with Parkinson's disease
Methods
randomized to either weekly intravenous infusions of NAC (50 mg/kg) plus oral doses (500 mg twice per day) for six months plus standard of care, or standard of care only
Blinding
Open-label
Duration
six months
Funding
Unclear

Introduction

This study assessed the changes in functional connectivity from resting functional magnetic resonance imaging (fMRI) in patients with Parkinson's disease (PD) given N-Acetylcysteine (NAC), the prodrug to L-cysteine and a precursor to the natural biological antioxidant glutathione (GSH). The aim of this study was to determine whether NAC is associated with changes in functional connectivity, particularly in the basal ganglia, and improvements in Parkinson's symptoms.

Methods

Forty-four patients with PD were randomized to either weekly intravenous infusions of NAC (50 mg/kg) plus oral doses (500 mg twice per day) for six months plus standard of care, or standard of care only. Participants received pre and post brain imaging with resting Blood Oxygen Level Dependent (BOLD) MRI to measure functional connectivity between key brain regions involved with PD. These findings were compared to changes in PD symptoms as measured by the Unified Parkinson's Disease Rating Scale (UPDRS).

Results

There were significant differences in the NAC group compared to the control group in functional connectivity measures after NAC. Specifically, there was significantly different functional connectivity between basal ganglia structures and the precuneus, precentral gyrus, postcentral gyrus, and particularly the Rolandic operculum. Changes in the precuneus also correlated with changes in UPDRS scores.

Conclusion

The results suggest that NAC may positively affect brain functional connectivity in PD patients, with corresponding positive clinical effects. Larger scale studies are warranted.

Research Insights

  • N-Acetyl Cysteine→Changed Functional Connectivity

    There were significant differences in the NAC group compared to the control group in functional connectivity measures after NAC. Specifically, there was significantly different functional connectivity between basal ganglia structures and the precuneus, precentral gyrus, postcentral gyrus, and particularly the Rolandic operculum.

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    50 mg/kg weekly IV + 500 mg twice per day oral
  • N-Acetyl Cysteine→Improved Parkinson's Disease Symptoms

    Changes in the precuneus also correlated with changes in UPDRS scores.

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    50 mg/kg weekly IV + 500 mg twice per day oral
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