Increased frontal [¹²³I]FP-CIT binding in Parkinson's disease patients with self-reported REM sleep behavior disorder

Rapid eye movement (REM) sleep behavior disorder (RBD) is a frequent non-motor symptom of Parkinson's disease (PD) and a potential early marker of synucleinopathy-related neurodegeneration. While striatal dopaminergic dysfunction in PD-RBD has been extensively studied, the role of extrastriatal monoaminergic alterations -particularly those involving serotonin - remains poorly understood. In this study, 155 PD patients underwent [¹²³I]FP-CIT SPECT imaging to assess striatal and extrastriatal tracer binding, reflecting dopaminergic and broader monoaminergic function, respectively. Probable RBD was identified using a validated single-question screening tool with high sensitivity and specificity. Patients with probable RBD (RBD + , n = 44) were compared to those without (RBD - , n = 111) using voxel-wise and region-of-interest analyses, controlling for age, sex, disease duration, motor and non-motor symptom severity, and cognitive function. No significant differences were observed in striatal dopamine transporter binding. However, RBD+ patients showed significantly higher extrastriatal binding in the prefrontal cortex (pFWE < 0.05), suggesting a potential role for altered extrastriatal monoaminergic neurotransmission, possibly involving serotonergic pathways, in PD-RBD pathophysiology. These findings should be interpreted with caution due to the non-selective binding profile of the radiotracer.