Reorganization of intrinsic functional connectivity in early-stage Parkinson's disease patients with probable REM sleep behavior disorder.

REM sleep behavior disorder (RBD) symptoms in Parkinson's disease (PD) suggest both a clinically and pathologically malignant subtype. However, whether RBD symptoms are associated with alterations in the organization of whole-brain intrinsic functional networks in PD, especially at early disease stages, remains unclear. Here we use resting-state functional MRI, coupled with graph-theoretical approaches and network-based statistics analyses, and validated with large-scale network analyses, to characterize functional brain networks and their relationship with clinical measures in early PD patients with probable RBD (PD+pRBD), early PD patients without probable RBD (PD-pRBD) and healthy controls. Thirty-six PD+pRBD, 57 PD-pRBD and 71 healthy controls were included in the final analyses. The PD+pRBD group demonstrated decreased global efficiency (t = -2.036, P = 0.0432) compared to PD-pRBD, and decreased network efficiency, as well as comprehensively disrupted nodal efficiency and whole-brain networks (all eight networks, but especially in the sensorimotor, default mode and visual networks) compared to healthy controls. The PD-pRBD group showed decreased nodal degree in right ventral frontal cortex and more affected edges in the frontoparietal and ventral attention networks compared to healthy controls. Furthermore, the assortativity coefficient was negatively correlated with Montreal cognitive assessment scores in the PD+pRBD group (r = -0.365, P = 0.026, d = 0.154). The observation of altered whole-brain functional networks and its correlation with cognitive function in PD+pRBD suggest reorganization of the intrinsic functional connectivity to maintain the brain function in the early stage of the disease. Future longitudinal studies following these alterations along disease progression are warranted.

High-frequency rTMS over the supplementary motor area improves freezing of gait in Parkinson's disease: a randomized controlled trial.

INTRODUCTION: Freezing of gait (FOG) contributes to falls in Parkinson's disease (PD), but robust, effective treatments remain elusive. There is evidence indicating that the supplementary motor area (SMA) plays an important role in the pathogenesis of FOG and may therefore be a potential neuromodulation target. The present study explored the clinical efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the SMA on FOG in PD patients. METHODS: A group of 30 PD patients with FOG were enrolled in a randomized, double-blind, sham-controlled trial. Patients were randomly allocated 2:1 to receive ten sessions of either real (N = 20) or sham (N = 10) 10 Hz rTMS over SMA. The patients were assessed at baseline (T0), after the 5th (T1) and 10th (T2) sessions, and then 2 weeks (T3) and 4 weeks (T4) after the last session. The primary clinical outcome was the Freezing of Gait Questionnaire score (FOGQ), with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor scores (MDS-UPDRS III) and Timed Up and Go test as secondary clinical outcomes. All the assessments were carried out at the "ON" state. RESULTS: With a four week's follow-up, there were significant interaction effects in the FOGQ (effect of group*time, p = 0.04), MDS-UPDRS III (p = 0.02) and several gait variables (total duration, p < 0.01; cadence, p = 0.04; turn duration, p = 0.01; and turn to sit duration, p = 0.02). Post-hoc analyses revealed a significantly decreased FOGQ score at T2 and T4, and significant improvements of MDS-UPDRS III and gait variables at T1, T2, T3 and T4 in the rTMS group. No significant improvements were found in the sham group. CONCLUSION: High-frequency rTMS over SMA may ultimately serve as an add-on therapy for alleviating FOG in PD patients.

Olfactory Dysfunction in Parkinson's Disease Patients with the LRRK2 G2385R Variant.

Olfactory dysfunction has been reported in Parkinson's disease (PD) patients carrying the LRRK2 G2019S variant in Caucasians but rarely in those with the LRRK2 G2385R variant. In this study, we performed genotyping for the LRRK2 G2385R variant in PD patients recruited from the Movement Disorder Clinic of Xuanwu Hospital in Beijing and in healthy controls randomly selected from the Beijing Longitudinal Study on Aging cohort. The "five-odor olfactory detection array", an olfactory threshold test, was used to assess olfactory function. One hundred and eighty-six participants were enrolled, comprising 43 PD patients without (iPD) and 25 with (LRRK2-PD) the LRRK2 G2385R variant, and 118 healthy controls. Our results showed that the threshold of olfactory identification was significantly worse in PD patients than in controls, but not significantly different between the iPD and LRRK2-PD groups. These findings suggested that although olfactory function in LRRK2-PD patients is impaired, it is similar to that in iPD patients.