GABA outperforms iron and neuromelanin in detecting nigrostriatal alterations in early-stage Parkinson’s disease with RBD

This study aimed to examine variations in iron deposition, neuromelanin (NM) content, gamma-aminobutyric acid (GABA) and glutamate-glutamine complex (Glx) levels within the nigrostriatal pathway in early-stage Parkinson’s disease (PD) patients with and without Rapid Eye Movement Sleep Behavior Disorder (RBD). Twenty-two early-stage PD patients with RBD (PD-RBD), 33 without RBD (PD-nRBD), and 36 healthy controls (HC) were prospectively recruited and underwent 3 T MRI and 1H-MRS scans. GABA levels in the left basal ganglia were elevated in PD-nRBD versus HC (P = 0.014), whereas they were decreased in the PD-RBD relative to the PD-nRBD (P = 0.018). Iron deposition and NM content in the bilateral substantia nigra (SN) showed no differences between PD subgroups. Despite similar SN iron and NM content, the GABAergic system alteration provides novel insights into the pathophysiology of RBD in PD.