Five-Year Longitudinal Trajectories of Non-Motor Symptoms in Relation to Baseline Dopaminergic Decline in Parkinson’S Disease Publisher



Mozafar M ; Mirhosseini H ; Farahani S ; Harandi H ; Garousi S ; Samadian F ; Rezaei A ; Hamidi H ; Jameie M ; Rezaei S ; Mottahedi M ; Mayeli M
Source: Brain Disorders Published:2025

Abstract

Introduction While Non-motor symptoms (NMS) in Parkinson’s disease (PD) substantially affect quality of life, their association with dopaminergic dysfunction remains unclear. This study examined longitudinal associations between NMS and striatal dopamine transporter single-photon emission computed tomography (DaT-SPECT) measures over five years in PD patients. Methods We studied 258 PD patients from the Parkinson’s Progression Markers Initiative (PPMI). The associations between the baseline DaT-SPECT-derived specific binding ratios (SBR) in the caudate, putamen, and striatum and longitudinal NMS, including rapid eye movement sleep behavior disorder (RBD), Epworth Sleepiness Scale, impulsivity, depression, anxiety, cognition, and olfaction were investigated. Results Greater caudate SBR asymmetry at baseline was associated with poorer visuospatial reasoning at year 2 (p < 0.001). Lower initial putamen and striatal SBR correlated with impaired verbal memory retention at year 3 (p < 0.001). Reduced baseline bilateral putamen SBR were linked to deficits in working memory and executive function at year 4 (p < 0.001). Decreased baseline putamen uptake was associated with higher anxiety five years after diagnosis (p < 0.001). Lower baseline caudate and striatal uptake was noted in PD patients who manifested depression 4–5 years later, whereas diminished baseline caudate, putamen, and striatal SBR was detected in those who exhibited RBD five years post-diagnosis (p < 0.05). Predictive modeling indicated modest diagnostic accuracy, with olfactory dysfunction best distinguished using the asymmetry index (AUC > 0.6). Conclusion Reduced striatal dopamine uptake, particularly in the caudate and putamen, was associated with progression of NMS including anxiety, depression, memory loss, visuospatial impairment, and RBD. Baseline DaT-SPECT may serve as a useful tool for anticipating NMS trajectories in PD. © 2025 Elsevier B.V., All rights reserved.