Does the pattern of striatal dopamine depletion contribute to non-motor symptoms in Parkinson's disease?

Abstract

Background : Non-motor symptoms (NMS) has been recognized as a key determinant factor for quality of life in Parkinson’s disease (PD), but the mechanism underlying NMS in PD has not yet been elucidated well. To investigate whether the pattern of striatal dopamine depletion contributes to NMS in PD, we hypothesized that PD patients with greater NMS might have a different pattern of striatal dopamine depletion, particularly the areas other than the posterior putamen, compared to those with less NMS.

Methods : We conducted a survey of the degree of NMS (using non-motor symptoms scale, NMSS) in 151 PD patients who had been initially diagnosed at our hospital by dopamine transporter (DAT) scanning, using a [18F] N-(3-Fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane (FP-CIT) PET scan (from March 2009 to June 2013).

Results : Patients with a high NMSS score (above the median) had an older age of PD onset (64.9 ± 9.1 vs 61.5 ± 10.1 years, p = 0.034), a higher initial part III of the Unified Parkinson Disease rating scale (UPDRS-motor, assessed in drug-na？ve state) (26.9 ± 11.7 vs 20.9 ± 10.3, p = 0.003), a higher levodopa- equivalent dose (636.3 ± 293.0 vs 524.4 ± 196.2, p = 0.007), and a greater Beck Depression Inventory (BDI) score (14.7 ± 8.1 vs 11.5 ± 7.5, p = 0.013), compared to those with a low NMSS score. A general linear model showed that patients with a high NMSS score had significantly higher UPDRS-motor score than those with a low score after controlling for onset age, gender, symptom duration, BDI score, and DAT activity in the posterior putamen (p = 0.034). However, DAT activities in 6 striatal subregions and inter-subregional ratios (ISRs) were comparable between the two groups. There were no correlations between subregional DAT activities and NMSS scores (either total or each domain scores), except for the mood/cognition domain score, which was negatively correlated to the anterior putamen/posterior putamen ISR (r = -0.175, p = 0.032).

Conclusion : This study demonstrates that the pattern of striatal dopamine depletion does not contribute to the degree of NMS in early PD, although some clinical features are different between the patients with greater NMS and those with less NMS. This study also suggests that patients with less NMS may have a benign course of motor symptom progression, compared to those with more NMS. NMS in PD may be more likely associated with extra-striatal lesions accompanied in PD than striatal dopaminergic deficits.