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Background: First-line rehabilitative strategies to improve motor deficits are based on functional training (physical or occupational therapy), which has been demonstrated to facilitate neural reorganisation. Accumulating evidence suggests that non-invasive brain stimulation techniques, such as repetitive TMS (rTMS), may enhance neuroplasticity, thereby facilitating neural reorganisation and recovery from Parkinson's disease. Evidence also shows that intermittent theta-burst stimulation (iTBS) can improve motor function and quality of life in patients by promoting the excitability and neural remodelling of cerebral cortex. We aimed to combine iTBS stimulation with physiotherapy to improve the rehabilitation effect compared to physiotherapy alone in patients with Parkinson's disease., Methods: This randomised, double-blind clinical trial will enrol 50 Parkinson's disease patients aged 45-70 years with Hoehn and Yahr scale scores of 1-3. Patients are randomly assigned to either the iTBS + physiotherapy or sham-iTBS + physiotherapy group. The trial consists of a 2-week double-blind treatment period and a 24-week follow-up period. iTBS and sham-iTBS will be administered twice daily for 10 days based on physiotherapy. The primary outcome will be the third part of Movement Disorders-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) from the baseline to the first 2 days following completion hospitalised intervention. The secondary outcome will be 39-item Parkinson's Disease Questionnaire (PDQ-39) at 4 weeks, 12 weeks and 24 weeks after intervention. Tertiary outcomes are clinical evaluations and mechanism study outcomes such as NMSS, 6MWD, 10MT, TUG, BBS, MRI, and EEG, the length of time between the drug needs to be adjusted when symptoms fluctuate., Discussion: The aim of this study is to demonstrate that iTBS can promote overall function and quality of life in Parkinson's disease patients using physiotherapy and that this efficacy may be associated with altered neuroplasticity in exercise-related brain regions. The iTBS combined with physiotherapy training model will be evaluated during a 6-month follow-up period. With significant improvement in quality of life and motor function, iTBS combined with physiotherapy can be considered as a first-line rehabilitation option for Parkinson's disease. The potential of iTBS to enhance neuroplasticity in the brain should have a more positive impact in increasing the generality and efficiency of physiotherapy, improving the quality of life and overall functional status of patients with Parkinson's disease., Trial Registration: Chinese Clinical Trial Registry ChiCTR2200056581. Registered on 8 February 2022., (© 2023. The Author(s).)

Introduction: Numerous studies have been carried out to explore the potential association between neurologic deficits and variable clinical manifestations of Parkinson's disease (PD). The aim of our study was to investigate the association between cognitive performance and motor dysfunction in Chinese patients with PD., Methods: Data from 96 patients with PD were obtained from the Parkinson's disease patient cohort database of Huashan Hospital. All participants underwent a comprehensive neuropsychological evaluation to assess cognitive status, that included scoring on the Mini-mental state examination (MMSE), followed by more detailed cognitive assessment on five main cognitive domains (verbal memory, nonverbal memory, visuospatial function, language and attention/executive function). Correlations between cognitive and motor scores were investigated after controlling for age, disease duration, education, and gender., Results: We report a significant correlation between subdomains of cognitive impairment and motor dysfunction using analyses of the multiple linear regression. Notably, executive function and attention was significantly associated with bradykinesia and rigidity, while visuospatial function was associated with bradykinesia and tremor., Conclusions: The association between motor dysfunction and cognitive decline in PD might highlight deficits represented by a shared neurochemical pathway.

Background: Olfactory identification was reported to be better among PD (Parkinson disease) patients with Parkin mutations, but previous studies didn't eliminate the interference of other PD related genes on olfaction, and whether olfaction of Parkin mutations patients was better in Chinese population was still unknown., Objective: To assess olfaction function among PD patients with Parkin mutations in Chinese population., Materials and Methods: A total of 226 PD patients with a positive family history or an early-onset age (<50 years) were enrolled for genetic testing of PD related genes by target sequencing and multiple ligation-dependent probe amplification. The clinical data including olfactory function test were investigated. Linear regression was performed to adjust for the covariates between all groups., Results: There were 68 patients found having a negative result in PD genetic testing and 43 patients carrying homozygous or compound heterozygous Parkin mutations. Among them, 49 PD panel negative patients and 33 PD- Parkin patients had results of olfactory assessment. PD -Parkin patients performed significantly better on the Sniffin' Sticks tests than panel negative patients (8.0 ± 1.7 vs. 5.7 ± 1.9, p  <   .001), but still worse compared to healthy controls (9.4 ± 1.5, p  =   .003). These differences persisted after adjusting for confounders., Conclusions: Among Chinese population, PD -Parkin patients had relatively preserved olfaction compared to PD panel negative patients after eliminating the interference of other PD related genes, but were still worse than healthy controls.

Background: Leucine-rich repeat kinase 2 gene (LRRK2) was recognized associated with both familial and sporadic Parkinson Disease (PD). Seven missense mutations (G2019S, R1441C, R1441G, R1441H, Y1699C, I2020T, N1437H) of it have been confirmed disease- causing. They were common among Caucasian PD patients, but rarely reported in Asian, especially in Chinese Han population., Objectives: We aimed to identify the frequencies of these seven mutations of LRRK2 in Chinese early-onset PD (EOPD) patients and analyze the phenotypes., Methods: One hundred and thirty seven EOPD patients were enrolled for genetic testing. The seven disease-causing mutations of LRRK2 were carried out by target sequencing using Illumina HiSeq 2000 Sequencer. The identified variants were further confirmed by Sanger sequence. The clinical materials were investigated retrospectively., Results: Only one patient (0.73%) was found carrying pathogenetic LRRK2 mutation of R1441C. The age at onset of the female patient was 44. She manifested typical motor symptoms of PD and responded well to levodopa therapy. Longitudinal evaluation showed progression of motor symptoms and depression but no cognitive impairment. The dopamine transporter (DAT) imaging via [11C]-2β-carbomethoxy-3β-(4-fluorophenyl) tropan (CFT) and Positron emission computed tomography (PET) revealed typical dopamine transporter uptake reduction., Conclusions: The LRRK2 R1441C mutation was found in a Chinese EOPD patient for the first time. The manifestations of LRRK2-R1441C carriers were indistinguishable from sporadic PD patients., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Olfactory dysfunction is common in Parkinson's disease (PD) and idiopathic rapid eye movement sleep behavior disorder (iRBD), which is a risk factor in the development of PD. However, a few studies have conflicting results when comparing dysosmia in the patients with iRBD and PD. There is no study investigating the olfactory function in Chinese patients with iRBD. Additionally, the Sniffin' Sticks screening 12 test (SS-12) contains several odors that are not familiar to people in different cultures., Methods: Odor identification was evaluated in iRBD patients (n = 54), PD patients (n = 54) and healthy controls (n = 54). With the identification data, a brief odor identification test was established and then validated in other subjects., Results: Odor identification scores in iRBD patients were significantly higher than those in PD patients (P<0.001) but lower than those in controls (P<0.001). At the cut-off value of 7.5, the Sniffin' Sticks clearly differentiated iRBD and PD patients from the controls, and the brief test could increase the specificity in diagnosing PD. Neither the Sniffin' Sticks nor the brief test could clearly differentiate PD and iRBD patients from each other., Conclusions: Olfaction is more impaired in PD patients than in iRBD patients, possibly due to the heterogeneity of iRBD patients. The Sniffin' Sticks could be a useful tool for differentiating iRBD patients from the healthy population, and it could be useful for screening people at high-risk of PD in China, especially when combined with polysomnography. To reduce the expense and time required for the Sniffin' Sticks test, this study shows that a brief test is feasible.

Purpose: The young-onset subtype of Parkinson's disease (YOPD) differs from the late-onset subtype (LOPD) in drug responsiveness, incidence of motor complications, and prognosis. The pathophysiology underlying these differences remains largely unknown. This study investigated whether the two subtypes differ in the pattern of dysfunction in striatal (caudate and putamen) dopaminergic system and if the dopamine transporter (DAT) imaging patterns are associated with the clinical features of corresponding PD subtype., Methods: We assessed the spatial pattern of striatal dopaminergic dysfunction in 40 YOPD and 47 LOPD with early to mid-stage PD with DAT imaging by positron emission tomography. Two sub-regional parameters (caudate/putamen ratio and asymmetry index) were calculated to measure the spatial pattern of striatal dopaminergic dysfunction., Results: The caudate/anterior putamen ratios were significantly higher in YOPD than that in the LOPD (P = 0.03 contralateral to the most affected side of the body and P = 0.004 ipsilateral), which was supported by significantly inverse correlations between age of onset and caudate/anterior putamen ratios (r = -0.428, P < 0.001 for the contralateral and r = -0.576, P < 0.001 for the ipsilateral). Sub-regional DAT binding in caudate ipsilateral to affected limbs was significantly correlated with age, while DAT bindings in putamen were significantly inversely correlated with disease duration and UPDRS motor scores., Conclusion: The YOPD subtype suffers from an uneven pattern of dopaminergic dysfunction: more sparing of the caudate compared with the putamen, while the LOPD patients is with a relatively uniform pattern., (Copyright © 2015 Elsevier Ltd. All rights reserved.)