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

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.