Title: Non-motor symptoms and striatal dopamine transporter binding in early Parkinson's disease.
Authors: Liu, Rui; Umbach, David M; Tröster, Alexander I; Huang, Xuemei; Chen, Honglei
Published In Parkinsonism Relat Disord, (2020 03)
Abstract: Non-motor symptoms (NMS) are common in Parkinson's disease (PD), but their relationships to nigrostriatal degeneration remain largely unexplored.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.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: βAVG = -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 (βAVG=0.055, SE = 0.022; p = 0.01) and visuospatial (βAVG=0.044, SE = 0.020; p = 0.03) cognitive domains, and negatively for total anxiety (βAVG= -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.Multiple NMS, RBD symptoms in particular, are associated with nigrostriatal dopaminergic changes in early PD.
PubMed ID: 32092703
MeSH Terms: Aged; Anxiety*/diagnostic imaging; Anxiety*/metabolism; Anxiety*/physiopathology; Autonomic Nervous System Diseases/diagnostic imaging; Autonomic Nervous System Diseases/etiology; Autonomic Nervous System Diseases/metabolism; Autonomic Nervous System Diseases/physiopathology; Cognitive Dysfunction*/diagnostic imaging; Cognitive Dysfunction*/etiology; Cognitive Dysfunction*/metabolism; Cognitive Dysfunction*/physiopathology; Depression/diagnostic imaging; Depression/etiology; Depression/metabolism; Depression/physiopathology; Disruptive, Impulse Control, and Conduct Disorders/diagnostic imaging; Disruptive, Impulse Control, and Conduct Disorders/etiology; Disruptive, Impulse Control, and Conduct Disorders/metabolism; Disruptive, Impulse Control, and Conduct Disorders/physiopathology; Dopamine Plasma Membrane Transport Proteins/pharmacokinetics*; Female; Humans; Longitudinal Studies; Male; Middle Aged; Neostriatum/diagnostic imaging; Neostriatum/metabolism*; Olfaction Disorders/diagnostic imaging; Olfaction Disorders/etiology; Olfaction Disorders/metabolism; Olfaction Disorders/physiopathology; Parkinson Disease*/complications; Parkinson Disease*/diagnostic imaging; Parkinson Disease*/metabolism; Parkinson Disease*/physiopathology; REM Sleep Behavior Disorder*/diagnostic imaging; REM Sleep Behavior Disorder*/etiology; REM Sleep Behavior Disorder*/metabolism; REM Sleep Behavior Disorder*/physiopathology; Substantia Nigra/diagnostic imaging; Substantia Nigra/metabolism*; Tomography, Emission-Computed, Single-Photon