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Introduction: Freezing of gait is a common complaint in patients with Parkinson's disease (PD). However, the neural bases of freezing of gait in PD remain uncertain. Existing studies on PD patients with freezing of gait (PD-FOG+) have reported damage of the corpus callosum, the largest commissural bundle of the brain. Thus, in this study we explored homotopic connectivity to investigate FOG-related interehemispheric alterations METHODS: A total of 21 PD-FOG + patients, 33 PD patients without freezing of gait (PD-FOG-), and 24 matched healthy controls were recruited. All PD patients were evaluated via the FOG questionnaire (FOGQ) and all subjects had a resting state functional magnetic resonance imaging (rs-fMRI) scan. The pattern of the homotopic connectivity was measured with the voxel-mirrored homotopic connectivity (VMHC) approach.Result: The PD-FOG + patients showed decreased VMHC values in the inferior parietal lobe (IPL) compared to both PD-FOG-patients and healthy controls. In PD-FOG + patients, the mean VMHC values in the IPL were negatively correlated with the FOGQ scores. Receiver operating characteristic curves analyses revealed that the VMHC in the IPL had discriminatory function distinguishing PD-FOG + patients from PD-FOG-patients or healthy controls.Conclusion: Decreased VMHC values of PD-FOG + patients relative to PD-FOG- and healthy controls in IPL maybe a unique feature for PD-FOG+ and it may have the ability to separate PD-FOG + patients from PD-FOG- and healthy controls. [ABSTRACT FROM AUTHOR]

Abstract: Previous studies on the association between glycogen synthase kinase 3 beta (GSK3-β) polymorphisms (rs334558 and rs6438552) and Parkinson's disease (PD) susceptibility remained inconsistent. Thus, the goal of this study was to re-examine their exact association by a meta-analysis. All eligible studies were identified by a systematic literature search of multiple databases. Six studies (3105 cases and 4387 controls) on rs334558 and six studies (2579 cases and 4091 controls) on rs6438552 were included. The quality of these studies was generally good according to the Newcastle–Ottawa Scale (NOS). The meta-analysis showed null association between the two variants and PD susceptibility in all genetic models from the overall or Caucasian population. However, the analysis of rs334558 revealed that the risk of PD decreased in heterozygote, dominant or additive models (OR=0.60, 95% CI: 0.48, 0.74; OR=0.63, 95% CI: 0.51, 0.78; OR=0.82, 95% CI: 0.71, 0.94, respectively) from the Eastern Asian population. Moreover, the analysis on the homozygote, heterozygote, dominant or additive models suggested that rs6438552 also reduced the PD risk (OR=0.45, 95% CI: 0.24, 0.84; OR=0.62, 95% CI: 0.39, 0.97; OR=0.57, 95% CI: 0.37, 0.87; OR=0.66, 95% CI: 0.49, 0.88, respectively) in the Eastern Asian population. Together, the findings suggest that the two variants both reduced the risk of PD in the Eastern Asian subgroup but not in the overall and Caucasian populations, which should be cautiously interpreted because of limited number of included studies. [Copyright &y& Elsevier]

Object To detect the cerebral metabolic bases of Parkinson’s disease (PD) patients with anxiety. Methods Totally 28 idiopathic PD patients without depression (17-item Hamilton Depression Rating Scale, HAMD score <14) were enrolled in our study. All subjects were classified into PD with anxiety (PD-A) (n = 13) and PD without anxiety (PD-NA) (n = 15) by cutoff score of 11 according to Hamilton Anxiety Rating Scale (HAMA). Besides, age- and gender- matched healthy controls (HCs) (n = 15) were selected. A resting-state F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scan was applied to estimate cerebral metabolic activity. All statistical analyses were performed using IBM SPSS Statistics V20.0.0 software, while statistical parametric mapping software (SPM) was used to analyze the FDG-PET images. Results PD-A showed decreased glucose metabolism in the bilateral orbitofrontal cortex (OFC, BA10 and BA11) when compared with PD-NA. Significant decrease of cerebral glucose metabolism in the bilateral OFC, bilateral supplementary motor area (SMA, BA6), bilateral dorsal anterior cingulate cortex (dACC, BA32), right dorsolateral prefrontal cortex (dlPFC, BA9), right ventrolateral prefrontal cortex (vlPFC, BA44), right putamen and left caudatum was detected in PD-A compared with HCs. There was significant reduced glucose metabolism of the bilateral SMA in PD-NA when compared with HCs (uncorrected p < 0.005). Conclusion The anxiety of PD was associated with the metabolic reductions of PFC and striatal areas. OFC, part of PFC, could be taken as a characteristic feature for anxiety in PD. This metabolic pattern suggested that deficits of prefrontostriatal pathways might affect anxiety mood in PD. [ABSTRACT FROM AUTHOR]

Background Accumulating evidence suggests that serotonergic system may be implicated in the pathophysiology of Parkinson's disease (PD), and particularly in nonmotor symptoms such as depression, fatigue, sleep disorders, sensory and autonomic dysfunction. This study aimed to evaluate plasma levels of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in PD patients, and investigate their associations with nonmotor symptoms. Methods Eighty-two PD patients and sixty-four controls underwent a series of clinical assessments, including Hamilton Depression Scale, Fatigue Severity Scale, Pittsburgh Sleep Quality Index, Visual Analog Scale for Pain, and Scale for Outcomes in PD for Autonomic Symptoms. Plasma 5-HT and 5-HIAA levels were measured by HPLC-ECD. Results PD patients exhibited worse performance on nonmotor symptom scales (all P -values <0.001) and presented lower plasma levels of 5-HT ( P < 0.001) and 5-HIAA ( P < 0.001) than control individuals. Within the PD group, decreased concentrations of plasma 5-HT and 5-HIAA were correlated with more severe depression (r = −0.447, P < 0.001; r = −0.407, P < 0.001, respectively) and pain (r = −0.485, P < 0.001; r = −0.416, P < 0.001, respectively). After performing multiple linear regression, plasma 5-HT ( P = 0.01) and 5-HIAA ( P = 0.006) remained significantly associated with depression. Conclusions Our results suggest that serotonergic dysfunction might exist in PD, and specifically correlated with depression and pain in PD. Plasma levels of 5-HT and 5-HIAA may be considered as peripheral markers for depression in PD. [ABSTRACT FROM AUTHOR]

Objectives: In this study, the alterations of structural topological properties in Parkinson's disease (PD) patients with levodopa-induced dyskinesias (LIDs) were explored using white matter structural network connectome derived from diffusion tensor imaging (DTI).Methods: 21 dyskinetic PD patients, 21 non-dyskinetic PD patients and 25 healthy controls were studied in global and nodal topological properties of structural networks after controlling age, gender and education. Afterwards, post hoc analyses were performed to explore further differences. Finally, multiple linear regression analysis was employed to test the associations between significant different properties and the severity of dyskinesias in PD.Results: Dyskinetic PD patients exhibited significant increased global efficiency, local efficiency, clustering coefficient, but decreased shortest path length compared with the non-dyskinetic. Additionally, increased nodal efficiency in bilateral inferior frontal gyrus (IFG), right putamen, right thalamus, and decreased nodal shortest path length in bilateral IFG and right thalamus, were discovered in dyskinetic PD in comparison with non-dyskinetic PD. Notably, a negative correlation between the Abnormal Involuntary Movement Scale (AIMS) scores and shortest path length of whole-brain network was found in PD with LIDs.Conclusions: Our results indicated excessively optimized topological organization of whole-brain structural connectome in PD patients with LIDs. These findings also illustrated that excessively strengthened basal ganglia-thalamocortical nodal structural connections played an important role in the presence of LIDs. [ABSTRACT FROM AUTHOR]

Object Anxiety disorders are very common in Parkinson’s disease (PD), but neural mechanisms underlying these symptoms still remain elusive. In the present study, we aim to investigate the neural substrates in anxiety disorders in PD. Methods The present study comprised 48 PD patients and 19 healthy subjects. According to a Hamilton Anxiety Rating Scale cutoff score of 12, we divided PD patients into PD with anxiety groups (n = 15) and PD without anxiety groups (n = 33). Patients with apparent depressive symptoms and cognitive decline were excluded. All subjects were evaluated for demographic and clinical characteristics and performed 3.0 T MRI scans. The alterations of neural activity were examined utilizing resting-state fMRI (rs-fMRI) combined with the amplitude of low-frequency fluctuations (ALFF) approach. Results Results of the analysis of covariance indicated that PD patients with anxiety displayed increased ALFF mainly in right cerebellar posterior lobe (CPL), bilateral brainstem and right orbitofrontal gyrus (OFG). Subsequently, the Spearman correlation demonstrated negative correlation between ALFF values in right cerebellum_9 and the Hamilton Anxiety Rating Scale scores. Conclusion Our findings demonstrated that anxiety disorders in PD were associated with increased activities in anxiety-related brain regions, including OFG, brainstem and CPL, using the ALFF approach. [ABSTRACT FROM AUTHOR]

• DFC in state IV differed between PD-pRBD and PD-npRBD. • FC among DMN, VIS and BG had abnormalities in pRBD. • Temporal metrics altered in RBD. Rapid eye movement (REM) sleep behavior disorder (RBD) is one of the common nonmotor symptoms of Parkinson's disease (PD), characterized by frequently occurring REM sleep without muscle atonia. Our aim was to explore dynamic network connection changes in PD patients with RBD. On the basis of RBD screening questionnaire (RBDSQ), 126 PD patients were classified into those with probable RBD symptoms (PD-pRBD) and without probable RBD (PD-npRBD). We applied independent component analysis, sliding window approach and k-means clustering methods to clarify dynamic functional connectivity alterations. In contrast to PD-npRBD, PD-pRBD patients were liable to engage in a brain pattern mainly marked by weaker positive couplings between visual network (VIS) and default mode network (DMN), DMN and basal ganglia network (BG), and within DMN (State IV). In addition, we discovered that both PD patients with or without pRBD had shorter dwell time and fewer occurrences in State III, characterized by positive correlations between VIS and DMN, BG and DMN, and positive within-network coupling of sensorimotor network (SMN), relative to healthy controls. Our study suggested that the weaker positive couplings between VIS and DMN, DMN and BG, and within DMN in State IV could be involved in the pathogenesis of PD patients with probable RBD on an overall level. [ABSTRACT FROM AUTHOR]

[Display omitted] • Peripheral sensory nerve was impaired in PD, MSA and PSP. • p-α-syn and p-tau in sural nerve may serve as novel biomarkers for differential diagnosis of PD, MSA and PSP. • Schwann cells might perform an important role in peripheral pathophysiological processes of PD, MSA and PSP. Differential diagnosis of Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear paralysis (PSP) is challenging. This study aimed to investigate the expression of phosphorylated α-synuclein (p-α-syn) and phosphorylated tau-protein (p-tau) in sural nerves from patients with PD, MSA and PSP to find biomarkers for differential diagnosis. Clinical evaluations and sural nerve biopsies were performed on 8 PD patients, 8 MSA patients, 6 PSP patients and 8 controls (CTRs). Toluidine blue staining was used to observe morphological changes in sural nerves. The deposition of p-α-syn and p-tau was detected by immunohistochemistry with semiquantitative evaluation. Locations of p-α-syn and p-tau were identified by double immunofluorescent staining. In case groups, the density of nerve fibres decreased with swollen or fragmented Schwann cells (SCs). All cases (22/22) but no CTRs (0/8) presented p-α-syn immunoreactivity with gradually decreasing semiquantitative levels among the PD (6.00 ± 2.07), MSA (5.00 ± 2.33) and PSP (3.50 ± 1.52) groups. p-tau aggregates were found in 7/8 MSA (1.88 ± 1.46) and 6/6 PSP (1.67 ± 0.52) patients but not in PD patients or CTRs. There were different expression patterns of p-α-syn and p-tau in PD, MSA and PSP patients. These findings suggest that peripheral sensory nerve injury exists in PD, MSA and PSP patients. With a different expression pattern and level, p-α-syn and p-tau in sural nerves may serve as novel biomarkers for differential diagnosis of PD, MSA and PSP. [ABSTRACT FROM AUTHOR]