Gender-specific effect of uric acid on resting-state functional networks in de novo Parkinson's disease

Introduction: The pattern of resting-state networks is influenced by several factors besides the underlying pathological changes of Parkinson's disease (PD). Uric acid (UA), as an antioxidant, has a neuroprotective property against PD-related microenvironment; however, this effect would be gender-specific. We aimed to evaluate a gender-sensitive resting-state networks (RSN) according to the UA level in drug naïve de novo patients with PD to elucidate the role of antioxidant in cortical functional networks of PD. Methods: This study enrolled 135 de novo patients with PD underwent functional magnetic resonance imaging (MRI). Based on the distribution, the serum UA level was stratified into tertiles in the PD patients by gender. With a seed-based approach, we investigated the pattern of RSN within the dorsal attention network (DAN), executive control network (ECN), and default mode network (DMN). Results: Interaction analysis showed a significant interaction between the lowest (PD-L-UA) and the highest UA level (PD-H-UA) groups according to gender within the DAN, ECN, and DMN. Compared to the control subjects, male patients with PD-H-UA had higher cortical functional connectivity (FC), while female patients had lower cortical FC regardless of UA level within all seeds. In a direct comparison, male patients with PD-H-UA had increased FC than did those with PD-L-UA. However, there was no significant difference in FC between PD-L-UA and PD-H-UA in female PD patients. Conclusions: These data suggest that RSN might be closely and gender-specifically associated with the status of serum UA in de novo PD patients.