Non-motor symptoms and striatal dopamine transporter binding in early Parkinson's disease

Background: Non-motor symptoms (NMS) are common in Parkinson's disease (PD), but their relationships to nigrostriatal degeneration remain largely unexplored. Methods: We evaluated 18 NMS scores covering 5 major domains in relation to concurrent and future dopamine transporter (DAT) imaging in 344 PD patients from the Parkinson's Progression and Markers Initiative (PPMI). We standardized NMS assessments into z-scores for side-by-side comparisons. Patients underwent sequential DaTSCAN imaging at enrollment and at months 12, 24, and 48. Specific binding ratios (SBR) were calculated using the occipital lobe reference region. We evaluated the association of striatal DAT binding at the four time points with each baseline NMS using mixed-effects regression models. Results: Multiple baseline NMS were significantly associated with DAT binding at baseline and at follow-up scans. REM sleep behavior disorder (RBD) symptoms showed the strongest association – mean striatal SBR declined with increasing RBD symptom z-score (average of time-point-specific slopes per unit change in z-score: β_AVG = −0.083, SE = 0.017; p < 0.0001). In addition, striatal DAT binding was linearly associated with increasing baseline z-scores: positively for the memory (β_AVG=0.055, SE = 0.022; p = 0.01) and visuospatial (β_AVG=0.044, SE = 0.020; p = 0.03) cognitive domains, and negatively for total anxiety (β_AVG= −0.059, SE = 0.018; p = 0.001). Striatal DAT binding showed curvilinear associations with odor identification, verbal discrimination recognition, and autonomic dysfunction z-scores (p = 0.001, p = 0.0009, and p = 0.0002, respectively). Other NMS were not associated with DAT binding. Conclusions: Multiple NMS, RBD symptoms in particular, are associated with nigrostriatal dopaminergic changes in early PD.