Tai Chi improves non-motor symptoms of Parkinson's disease: One-year randomized controlled study with the investigation of mechanisms.

BACKGROUND: Tai Chi was found to improve motor symptoms in Parkinson's disease (PD). Whether long-term Tai Chi training could improve non-motor symptoms (NMS) and the related mechanisms were unknown. OBJECTIVE: To investigate Tai Chi's impact on non-motor symptoms in PD and related mechanisms. METHODS: 95 early-stage PD patients were recruited and randomly divided into Tai Chi (N = 32), brisk walking (N = 31), and no-exercise groups (N = 32). All subjects were evaluated at baseline, 6 months, and 12 months within one-year intervention. Non-motor symptoms (including cognition, sleep, autonomic symptoms, anxiety/depression, and quality of life) were investigated by rating scales. fMRI, plasma cytokines and metabolomics, and blood Huntingtin interaction protein 2 (HIP2) mRNA levels were detected to observe changes in brain networks and plasma biomarkers. RESULTS: Sixty-six patients completed the study. Non-motor functions assessed by rating scales, e.g. PD cognitive rating scale (PDCRS) and Epworth Sleepiness scale (ESS), were significantly improved in the Tai Chi group than the control group. Besides, Tai Chi had advantages in improving NMS-Quest and ESS than brisk walking. Improved brain function was seen in the somatomotor network, correlating with improved PDCRS (p = 0.003, respectively). Downregulation of eotaxin and upregulation of BDNF demonstrated a positive correlation with improvement of PDCRS and PDCRS-frontal lobe scores (p ≤ 0.037). Improvement of energy and immune-related metabolomics (p ≤ 0.043), and elevation of HIP2 mRNA levels (p = 0.003) were also found associated with the improvement of PDCRS. CONCLUSIONS: Tai Chi improved non-motor symptoms in PD, especially in cognition and sleep. Enhanced brain network function, downregulation of inflammation, and enhanced energy metabolism were observed after Tai Chi training.

Relationships Between Rapid Eye Movement Sleep Behavior Disorder and Parkinson's Disease: Indication from Gut Microbiota Alterations.

Rapid eye movement sleep behavior disorder (RBD) has a close relationship with Parkinson's disease (PD) and was even regarded as the most reliable hallmark of prodromal PD. RBD might have similar changes in gut dysbiosis to PD, but the relationship between RBD and PD in gut microbial alterations is rarely studied. In this study, we aim to investigate whether there were consistent changes between RBD and PD in gut microbiota, and found some specific biomarkers in RBD that might indicate phenoconversion to PD. Alpha-diversity showed no remarkable difference and beta-diversity showed significant differences based on the unweighted (R = 0.035, P = 0.037) and weighted (R = 0.0045, P = 0.008) UniFrac analysis among idiopathic RBD (iRBD), PD with RBD, PD without RBD and normal controls (NC). Enterotype distribution indicated iRBD, PD with RBD and PD without RBD were Ruminococcus-dominant while NC were Bacteroides-dominant. 7 genera (4 increased: Aerococcus, Eubacterium, Gordonibacter and Stenotrophomonas, 3 decreased: Butyricicoccus, Faecalibacterium and Haemophilus) were consistently changed in iRBD and PD with RBD. Among them, 4 genera (Aerococcus, Eubacterium, Butyricicoccus, Faecalibacterium) remained distinctive in the comparison between PD with RBD and PD without RBD. Through clinical correlation analysis, Butyricicoccus and Faecalibacterium were found negatively correlated with the severity of RBD (RBD-HK). Functional analysis showed iRBD had similarly increased staurosporine biosynthesis to PD with RBD. Our study indicates that RBD had similar gut microbial changes to PD. Decreased Butyricicoccus and Faecalibacterium might be potential hallmarks of phenoconversion of RBD to PD.

Effect of long-term Tai Chi training on Parkinson's disease: a 3.5-year follow-up cohort study.

BACKGROUND: Tai Chi has shown beneficial effects on the motor and non-motor symptoms of Parkinson's disease (PD), but no study has reported the effect of long-term Tai Chi training. OBJECTIVE: To examine whether long-term Tai Chi training can maintain improvement in patients with PD. METHODS: Cohorts of patients with PD with Tai Chi training (n=143) and patients with PD without exercise as a control group (n=187) were built from January 2016. All subjects were assessed at baseline and in November 2019, October 2020 and June 2021. A logarithmic linear model was used to analyse rating scales for motor and non-motor symptoms. The need to increase antiparkinsonian therapies was presented as a Kaplan-Meier plot and as a box plot. The bootstrap method was used to resample for statistical estimation. RESULTS: Tai Chi training reduced the annual changes in the deterioration of the Unified Parkinson's Disease Rating Scale and delayed the need for increasing antiparkinsonian therapies. The annual increase in the levodopa equivalent daily dosage was significantly lower in the Tai Chi group. Moreover, patients benefited from Tai Chi training in motor symptoms, non-motor symptoms and complications. CONCLUSION: Tai Chi training has a long-term beneficial effect on PD, with an improvement in motor and non-motor symptoms and reduced complications. TRIAL REGISTRATION NUMBER: NCT05447975.

A Thermal-Ball-Valve Structure Separator for Highly Safe Lithium-Ion Batteries.

The separator located between the positive and negative electrodes not only provides a lithium-ion transmission channel but also prevents short circuits for direct contact of electrodes. The inferior dimension thermostability of commercial polyolefin separators intensifies the thermal runaway of batteries under abuse such as short circuits, overcharge, and so on. a polyvinylidene fluoride/polyether imide (PVDF/PEI) separator with high thermal stability in which the high thermostable PEI microspheres are evenly dispersed in the PVDF film matrix and also located in the micro holes of the PVDF film is developed. They not only function as strong skeleton that enables the rare shrink of the separator at 200 °C avoiding short circuit but also act as ball valve that blocks the lithium ion transmission channel at 150 °C interrupting the further heat aggregation. Thus, the LiNi0.6 Co0.2 Mn0.2 O2 /Li batteries exhibit high cycle stability of 96.5% capacity retention after 100 cycles at 0.2C and 80°C. Further, the LiNi0.6 Co0.2 Mn0.2 O2 /graphite pouch cells are constructed and deliver good safety performance without smoke release and catching fire after the nail penetration test.

Clinical safety and efficacy of allogenic human adipose mesenchymal stromal cells-derived exosomes in patients with mild to moderate Alzheimer's disease: a phase I/II clinical trial.

Background: There have been no effective treatments for slowing or reversing Alzheimer's disease (AD) until now. Growing preclinical evidence, including this study, suggests that mesenchymal stem cells-secreted exosomes (MSCs-Exos) have the potential to cure AD. Aims: The first three-arm, drug-intervention, phase I/II clinical trial was conducted to explore the safety and efficacy of allogenic human adipose MSCs-Exos (ahaMSCs-Exos) in patients with mild to moderate AD. Methods: The eligible subjects were assigned to one of three dosage groups, intranasally administrated with ahaMSCs-Exos two times per week for 12 weeks, and underwent follow-up visits at weeks 16, 24, 36 and 48. Results: No adverse events were reported. In the medium-dose arm, Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-cog) scores decreased by 2.33 (1.19) and the basic version of Montreal Cognitive Assessment scores increased by 2.38 (0.58) at week 12 compared with baseline levels, indicating improved cognitive function. Moreover, the ADAS-cog scores in the medium-dose arm decreased continuously by 3.98 points until week 36. There were no significant differences in altered amyloid or tau deposition among the three arms, but hippocampal volume shrank less in the medium-dose arm to some extent. Conclusions: Intranasal administration of ahaMSCs-Exos was safe and well tolerated, and a dose of at least 4×108 particles could be selected for further clinical trials. Trial registration number: NCT04388982.

Predicting the Prognosis of Multiple System Atrophy Using Cluster and Principal Component Analysis.

BACKGROUND: Multiple system atrophy (MSA) is an intractable neurodegenerative disorder with poorly understanding of prognostic factors. OBJECTIVE: The purpose of this retrospective longitudinal study was to explore the main predictors of survival of MSA patients with new clinical subtypes based on cluster analysis. METHODS: A total of 153 Chinese MSA patients were recruited in our study. The basic demographic data and motor and nonmotor symptoms were assessed. Cluster and principal component analysis (PCA) were used to eliminate collinearity and search for new clinical subtypes. The multivariable Cox regression was used to find factors associated with survival in MSA patients. RESULTS: The median survival time from symptom onset to death (estimated using data from all patients by Kaplan-Meier analysis) was 6.3 (95% CI = 6.1-6.7) years. The survival model showed that a shorter survival time was associated with motor principal component (PC)1 (HR = 1.71, 95% CI: 1.26-2.30, p < 0.001) and nonmotor PC3 (HR = 1.68, 95% CI: 1.31-2.10, p < 0.001) through PCA. Four clusters were identified: Cluster 1 (mild), Cluster 2 (mood disorder-dominant), Cluster 3 (axial symptoms and cognitive impairment-dominant), and Cluster 4 (autonomic failure-dominant). Multivariate Cox regression indicated that Cluster 3 (HR = 4.15, 95% CI: 1.73-9.90, p = 0.001) and Cluster 4 (HR = 4.18, 95% CI: 1.73-10.1, p = 0.002) were independently associated with shorter survival time. CONCLUSION: More serious motor symptoms, axial symptoms such as falls and dysphagia, orthostatic hypotension, and cognitive impairment were associated with poor survival in MSA via PCA and cluster analysis.

Meta-analysis of the association between dietary inflammatory index and cognitive health.

Background: Some studies have shown that a pro-inflammatory diet may be associated with cognitive function, but their conclusions have varied considerably. We here present a meta-analysis of the current published literature on DII score and its association with cognitive health. Methods: In this meta-analysis, the PubMed, Embase, Web of Science, and Cochrane databases were searched in September 2022. The reported indexes, specifically OR, RR, and ß, were extracted and analyzed using R version 3.1.0. Results: A total of 636 studies in databases were identified, and 12 were included in the meta-analysis. Higher DII was associated with an increased risk of AD and MCI (OR = 1.34; 95% CI = 1.21-1.49). Meanwhile, it may also cause global function impairment (categorical: OR = 1.63; 95% CI = 1.36-1.96) and verbal fluency impairment (continuous: OR = 0.18; 95% IC = 0.08-0.42). But there was no significant association between DII and executive function (categorical: OR = 1.12; 95% IC = 0.84-1.49; continuous: OR = 0.48; 95% IC = 0.19-1.21) or episodic memory (continuous: OR = 0.56; 95% IC = 0.30-1.03). Conclusion: A pro-inflammatory diet is related to AD, MCI, and the functions of some cognitive domains (specifically global function and verbal fluency). However, the current evidence on the role of diet-induced inflammation in different cognitive domains should be supported by further studies in the future.

Sex difference in biological change and mechanism of Alzheimer's disease: From macro- to micro-landscape.

Alzheimer's disease (AD) is the most common form of dementia and numerous studies reported a higher prevalence and incidence of AD among women. Although women have longer lifetime, longevity does not wholly explain the higher frequency and lifetime risk in women. It is important to understand sex differences in AD pathophysiology and pathogenesis, which could provide foundation for future clinical AD research. Here, we reviewed the most recent and relevant literature on sex differences in biological change of AD from macroscopical neuroimaging to microscopical pathologic change (neuronal degeneration, synaptic dysfunction, amyloid-beta and tau accumulation). We also discussed sex differences in cellular mechanisms related to AD (neuroinflammation, mitochondria dysfunction, oxygen stress, apoptosis, autophagy, blood-brain-barrier dysfunction, gut microbiome alteration, bulk and single cell/nucleus omics) and possible causes underlying these differences including sex-chromosome, sex hormone and hypothalamic-pituitary- adrenal (HPA) axis effects.

MAO-B Polymorphism Associated with Progression in a Chinese Parkinson's Disease Cohort but Not in the PPMI Cohort.

Introduction: Genetic factors play an important role in Parkinson's disease (PD) risk. However, the genetic contribution to progression in Chinese PD patients has rarely been studied. This study investigated genetic associations with progression based on 30 PD risk loci common in a longitudinal cohort of Chinese PD patients and the Parkinson's Progression Markers Initiative (PPMI) cohort. Methods: PD patients from the true world (TW) Chinese PD longitudinal cohort and the PPMI cohort with demographic information and assessment scales were assessed. A panel containing 30 PD risk single nucleotide polymorphisms was tested. Progression rates of each scale were derived from random-effect slope values of mixed-effects regression models. Progression rates of multiple assessments were combined by using principal component analysis (PCA) to derive scores for composite, motor, and nonmotor progression. The association of genetic polymorphism and separate scales or PCA progression was analysed via linear regression. Results: In the Chinese PD cohort, MAOB rs1799836 was associated with progression based on the Montreal Cognitive Assessment, the top 3 principal components (PCs) of nonmotor PCA and PC1 of the composite PCA. In the PPMI cohort, both MDS-Unified Parkinson's Disease Rating Scale II and motor PC1 progression were associated with RIT2 rs12456492. The PARK16 haplotype was associated with Geriatric Depression Scale and the State-Trait Anxiety Inventory for Adults progression, and the SNCA haplotype was associated with the Hoehn-Yahr staging progression and motor PC1 progression. Ethnicity-stratified analysis showed that the association between MAOB rs1799836 and PD progression may be specific to Asian or Chinese patients. Conclusion: MAOB rs1799836 was associated with the progression of nonmotor symptoms, especially cognitive impairment, and the composite progression of motor and nonmotor symptoms within our Chinese PD cohort. The RIT2 rs12456492 and SNCA haplotypes were associated with motor function decline, and the PARK16 haplotype was associated with progression in mood in the PPMI cohort.

Specific gut microbiota alterations in essential tremor and its difference from Parkinson's disease.

Essential tremor (ET) is the most common movement disorder and share overlapping symptoms with Parkinson's disease (PD), making differential diagnosis challenging. Gut dysbiosis is regarded crucial in the pathogenesis of PD. Since ET patients also has comorbidity in gastrointestinal disorders, the relationship between gut microbiota and ET really worth investigating and may help distinguishing ET from PD. Fecal samples from 54 ET, 67 de novo PD and 54 normal controls (NC) were collected for 16S ribosomal RNA gene sequencing and quantitative real-time PCR. ET showed lower species richness (Chao1 index) than NC and PD. ET was with Bacteroides-dominant enterotype, while PD was with Ruminococcus-dominant enterotype. Compared with NC, 7 genera were significantly reduced in ET, 4 of which (Ruminococcus, Romboutsia, Mucispirillum, and Aeromonas) were identified to be distinctive with an area under the curve (AUC) of 0.705. Compared to PD, 26 genera were found significantly different from ET, 4 of which (Bacteroides, Fusobacterium, Phascolarctobacterium, and Lachnospira) were found distinguishable with an AUC of 0.756. Clinical association results indicated that Proteus was associated with disease severity (TETRAS) of ET, while Klebsiella was linked to depression and anxiety in ET. Functional predictions revealed that 4 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were altered in ET. This study reveals gut dysbiosis in ET and it provides new insight into the pathogenesis of ET and helps distinguishing ET from PD.

The China Alzheimer Report 2022.

China's population has rapidly aged over the recent decades of social and economic development as neurodegenerative disorders have proliferated, especially Alzheimer's disease (AD) and related dementias (ADRD). AD's incidence rate, morbidity, and mortality have steadily increased to make it presently the fifth leading cause of death among urban and rural residents in China and magnify the resulting financial burdens on individuals, families and society. The 'Healthy China Action' plan of 2019-2030 promotes the transition from disease treatment to health maintenance for this expanding population with ADRD. This report describes related epidemiological trends, evaluates the economic burden of the disease, outlines current clinical diagnosis and treatment status and delineates existing available public health resources. More specifically, it examines the public health impact of ADRD, including prevalence, mortality, costs, usage of care, and the overall effect on caregivers and society. In addition, this special report presents technical guidance and supports for the prevention and treatment of AD, provides expertise to guide relevant governmental healthcare policy development and suggests an information platform for international exchange and cooperation.

Mechanisms of motor symptom improvement by long-term Tai Chi training in Parkinson's disease patients.

BACKGROUND: Tai Chi has been shown to improve motor symptoms in Parkinson's disease (PD), but its long-term effects and the related mechanisms remain to be elucidated. In this study, we investigated the effects of long-term Tai Chi training on motor symptoms in PD and the underlying mechanisms. METHODS: Ninety-five early-stage PD patients were enrolled and randomly divided into Tai Chi (n = 32), brisk walking (n = 31) and no-exercise (n = 32) groups. At baseline, 6 months and 12 months during one-year intervention, all participants underwent motor symptom evaluation by Berg balance scale (BBS), Unified PD rating-scale (UPDRS), Timed Up and Go test (TUG) and 3D gait analysis, functional magnetic resonance imaging (fMRI), plasma cytokine and metabolomics analysis, and blood Huntingtin interaction protein 2 (HIP2) mRNA level analysis. Longitudinal self-changes were calculated using repeated measures ANOVA. GEE (generalized estimating equations) was used to assess factors associated with the longitudinal data of rating scales. Switch rates were used for fMRI analysis. False discovery rate correction was used for multiple correction. RESULTS: Participants in the Tai Chi group had better performance in BBS, UPDRS, TUG and step width. Besides, Tai Chi was advantageous over brisk walking in improving BBS and step width. The improved BBS was correlated with enhanced visual network function and downregulation of interleukin-1ß. The improvements in UPDRS were associated with enhanced default mode network function, decreased L-malic acid and 3-phosphoglyceric acid, and increased adenosine and HIP2 mRNA levels. In addition, arginine biosynthesis, urea cycle, tricarboxylic acid cycle and beta oxidation of very-long-chain fatty acids were also improved by Tai Chi training. CONCLUSIONS: Long-term Tai Chi training improves motor function, especially gait and balance, in PD. The underlying mechanisms may include enhanced brain network function, reduced inflammation, improved amino acid metabolism, energy metabolism and neurotransmitter metabolism, and decreased vulnerability to dopaminergic degeneration. Trial registration This study has been registered at Chinese Clinical Trial Registry (Registration number: ChiCTR2000036036; Registration date: August 22, 2020).

Associations between the use of ß-adrenoceptor acting drugs and the risk of dementia in older population.

Objective: Age-related decline within the noradrenergic system is associated with reduced cognition. The ß-adrenoceptors are widely expressed in the brain as well as in the peripheral. Medications targeting ß-adrenoceptor activity have been widely used in older adults. The aim of this study was to explore the associations between ß-adrenoceptor acting drugs and the risk of dementia in the older population. Methods: The subjects' information was collected from the electronic medical record (EMR) database. A propensity score matching strategy was conducted to select control participants for users of ß2-agonists or ß-antagonists. Logistic regression analysis was performed to estimate the risk of dementia with the use of ß2-agonists or ß-antagonists. Results: A total of 1,429 participants in the EMR database were included in the study. The use of ß2-agonists was strongly associated with a decreased risk of dementia [OR = 0.324, 95% confidence interval (CI): 0.149-0.707, P = 0.005]. This decreased risk showed a statistically significant inverse time-dependent pattern (P trend = 0.014). However, the use of non-selective ß-antagonists significantly correlated with an increased dementia risk (OR = 1.961, 95% CI: 1.144-3.359, P = 0.014), although no time-dependent manner was found (P trend = 0.220). There was no association between selective ß1-antagonists usage and dementia risk (OR = 1.114, P = 0.625). Conclusion: The use of ß-adrenoceptor acting drugs seems to be associated with the risk of dementia. Pharmacological interventions modulating ß2-adrenoceptor activity might be a potential target in therapeutics for dementia.

Sex effects on clinical features in LRRK2 G2385R carriers and non-carriers in Parkinson's disease.

BACKGROUND: Differences of genotypes between male and female have been studied in Parkinson's disease (PD), but limited research has focused on the comparison between sexes with LRRK2 G2385 variant. OBJECTIVE: The aim of this study was to explore sex effects in the same genetic subtype and role of leucine-rich repeat kinase 2 (LRRK2) G2385R variants in the same sex in PD. METHODS: 613 PD patients were recruited from the Movement Disorders Clinic in Ruijin Hospital. We did not include healthy controls in this study. The data collected includes demographic information, disease history, scores of motor and non-motor symptoms scales, midbrain transcranial sonography and DNA. Binary logistic regression analysis was performed to evaluate the association between clinical features and sex in LRRK2 G2385R carriers and non-carriers, as well as the association between the clinical features and LRRK2 G2385R variants in male and female sex. RESULTS: Sex distribution is similar in LRRK2 G2385R carriers and non-carriers. In male sex, LRRK2 G2385R carriers showed lower risk in cognitive impairment compared with non-carriers (OR = 0.301, p = 0.003, 95%CI 0.135-0.668). In female sex, LRRK2 G2385R carriers showed lower risk in autonomic dysfunction compared with non-carrier (OR = 0.401, p = 0.040, 95%CI 0.167-0.960). In LRRK2 G2385R non-carriers, female sex showed lower risk of impairment in activity of daily living (OR = 0.610, p = 0.021, 95%CI 0.400-0.928), excessive daytime sleepiness (OR = 0.555, p = 0.007, 95%CI 0.361-0.853), substantia nigra hyperechogenicity (OR = 0.448, p = 0.019, 95%CI 0.228-0.878), autonomic dysfunction frequency (OR = 0.626, p = 0.016, 95%CI 0.428-0.917) and higher risk in mood disorders (OR = 1.691, p = 0.022, 95%CI 1.078-2.654) compared with male. In LRRK2 G2385R carriers, female sex showed a lower risk of autonomic dysfunction (OR = 0.294, p = 0.024, 95%CI 0.102-0.849) compared with male. CONCLUSION: In contrast to male PD patients, a more benign disease course was observed in female in both LRRK2 G2385R carriers and non-carriers. However, sex differences were less notable in PD with LRRK2 G2385R variants.

The Association Analysis of GPNMB rs156429 With Clinical Manifestations in Chinese Population With Parkinson's Disease.

Background: The mechanisms of Parkinson's disease (PD) include complicated genetic factors. The roles of newly found risk genes need to be further verified among different ethnicities. In a two-stage meta-analysis, single nucleotide polymorphism (SNP) of rs156429 in glycoprotein non-metastatic melanoma protein B (GPNMB) was reported to be associated with PD. So far clinical studies have focused on association between rs156429 and PD onset, however there is little evidence linking rs156429 with PD symptoms. Objective: This study aimed to investigate the possible association of GPNMB rs156429 with PD manifestations among southeastern Chinese people. Methods: Demographic variables, disease-related factors, and motor and non-motor assessments of 511 PD patients were collected. Polymerase chain reaction (PCR) and SNaPshot technique were used to detect GPNMB rs156429. The associations of rs156429 with PD rating scales and clinical manifestations were analyzed by Kruskal-Wallis test and logistic regression model separately. Results: Kruskal-Wallis test and logistic regression model failed to reveal an association between GPNMB rs156429 and scores from Montreal Cognitive Assessment (MoCA) (p = 0.037; p = 1.000 after correction), and pain symptoms of 511 PD patients (p = 0.008, OR = 0.59, 95% CI = 0.40-0.87, overdominant model after adjustment; p = 0.168 after correction, overdominant model after adjustment). However, further analysis based on genders showed that GPNMB rs156429 might have a trend for being associated with cognitive dysfunction (Mini-Mental State Examination (MMSE), p = 0.064 after correction; MoCA, p = 0.064 after correction) and pain symptoms (p = 0.063 after correction, overdominant model after adjustment) in female PD patients but not male patients. Conclusions: This study revealed that GPNMB rs156429 might have a trend for being associated with cognitive dysfunction and pain symptoms of female PD patients in the southeastern Chinese population. Further studies from a larger sample size are needed to confirm these findings.

Midbrain/pons area ratio and clinical features predict the prognosis of progressive Supranuclear palsy.

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare movement disorder with poor prognosis. This retrospective study aimed to characterize the natural history of PSP and to find predictors of shorter survival and faster decline of activity of daily living. METHOD: All patients recruited fulfilled the movement disorder society (MDS) clinical diagnostic criteria for PSP (MDS-PSP criteria) for probable and possible PSP with median 12 years. Data were obtained including age, sex, date of onset, age at onset (AAO), symptoms reported at first visit and follow-up, date of death and date of institutionalization. Magnetic resonance imaging was collected at the first visit. Endpoints were death and institutionalization. Kaplan-Meier method and Cox proportional hazard model were used to explore factors associated with early death and institutionalization. RESULTS: Fifty-nine patients fulfilling MDS-PSP criteria were enrolled in our study. Nineteen patients (32.2%) had died and 31 patients (52.5%) were institutionalized by the end of the follow-up. Predictors associated with poorer survival were late-onset PSP and decreased M/P area ratio. Predictors associated with earlier institutionalization were older AAO and decreased M/P area ratio. CONCLUSION: Older AAO and decreased M/P area ratio were predictors for earlier dearth and institutionalization in PSP. The neuroimaging biomarker M/P area ratio was a predictor for prognosis in PSP.

Validation of Revised Chinese Version of PD-CRS in Parkinson's Disease Patients.

There is a high prevalence of mild cognitive impairment (MCI) and dementia in Parkinson's disease (PD) patients, but a Chinese version of cognitive rating scale that is specific and sensitive to PD patients is still lacking. The aims of this study are to test the reliability and validity of a Chinese version of Parkinson's disease-cognitive rating scale (PD-CRS), establish cutoff scores for diagnosis of Parkinson's disease dementia (PDD) and PD with mild cognitive impairment (PD-MCI), explore cognitive profiles of PD-MCI and PDD, and find cognitive deficits suggesting a transition from PD-MCI to PDD. PD-CRS was revised based on the culture background of Chinese people. Ninety-two PD patients were recruited in three PD centers and were classified into PD with normal cognitive function (PD-NC), PD-MCI, and PDD subgroups according to the cognitive rating scale (CDR). Those PD patients underwent PD-CRS blind assessment by a separate neurologist. The PD-CRS showed a high internal consistency (Cronbach's Alpha = 0.840). Intraclass Correlation coefficient (ICC) of test-retest reliability reached 0.906 (95% CI 0.860-0.935, p < 0.001). ICC of inter-rater reliability was 0.899 (95% CI 0.848-0.933, p < 0.001). PD-CRS had fair concurrent validity with MDRS (ICC = 0.731, 95% CI 0.602-0.816). All the frontal-subcortical items showed significant decrease in PD-MCI compared with the PD-NC group (p ≤ 0.001), but the instrument cortical items did not (confrontation naming p=0.717, copying a clock p=0.620). All the frontal-subcortical and instrumental-cortical functions showed significant decline in PDD compared with the PD-NC group (p ≤ 0.001). The cutoff value for diagnosis of PD-MCI is 80.5 with the sensitivity of 75.7% and the specificity of 75.0%, and for diagnosis of PDD is 73.5 with the sensitivity of 89.2% and the specificity of 98.9%. Revised Chinese version of PD-CRS is a reliable, acceptable, valid, and useful neuropsychological battery for assessing cognition in PD patients.

Parkinson's disease in China: a forty-year growing track of bedside work.

The number and health burden of Parkinson's disease increase rapidly in China. It is estimated that China will have nearly half of the Parkinson's disease population in the world in 2030. In this review, we present an overview of epidemiology and health economics status of Parkinson's disease across China and discuss the risk factors of Parkinson's disease and related complications. From the view of clinical research, we also discuss the current status of clinical trials, diagnostic biomarkers, treatment of Parkinson's disease, tertiary network and post-occupation education in Chinese Parkinson's disease clinics.

Fecal and Blood Microbial 16s rRNA Gene Alterations in Chinese Patients with Multiple System Atrophy and Its Subtypes.

BACKGROUND AND OBJECTIVE: To explore the alterations of microbial 16s ribosomal (rRNA) gene in the feces and blood of Chinese patients with multiple system atrophy (MSA) and its relationships with clinical features. METHODS: 40 MSA patients (MSA-P/MSA-C: 23/17) and their healthy spouses were recruited. Fecal and blood microbiota were investigated by high-throughput IllUmina Miseq sequencing targeted on the V3-V4 functional region of 16s rRNA gene. The relationships between microbiota and clinical characteristics were analyzed. RESULTS: The abundances of Lactobacillus, Gordonibacter, Phascolarctobacterium, and Haemophilus in feces and abundances of Leucobacter, and Bacteroides in blood were different between MSA patients and healthy controls (HC). Combining the taxa from feces and blood, six genera were identified to be predictive of MSA, achieving an area under the curve (AUC) of 0.853. The abundances of Phascolarctobacterium and Ruminococcus in feces were lower in MSA-P than those in MSA-C. The abundances of Blastococcus, Bacillus, and Acinetobacter in blood were different between MSA subtypes. These five genera differentiated MSA subtypes with an AUC of 0.898. Functional predictions indicated that gene functions involving biosynthetic metabolism and bacterial secretion systems were significantly different between the MSA and HC. The differential genera were associated with disease duration, anxiety, and autonomic dysfunctions. CONCLUSIONS: We confirmed the alterations of microbial 16s rRNA gene in the feces and blood occurs in Chinese patients with MSA. Microbiota dysbiosis was related to MSA clinical manifestations. Elucidating these differences in microbiomes will be helpful to improve our knowledge of the microbiota in the pathogenesis of MSA.

IL1B polymorphism is associated with essential tremor in Chinese population.

BACKGROUND: The aim of the study was to investigate the genetic risk factors of essential tremor (ET) in Chinese Population. METHODS: A total of 225 ET patients (25 ET patients also had restless legs syndrome (RLS) and were excluded from final analysis) and 229 controls were recruited. The diagnosis of ET was based on the Consensus Statement of the Movement Disorders Society on tremor. Polymerase chain reaction (PCR) and sequencing were used to detect 12 single nucleotide polymorphisms (SNPs) in seven candidate genes for RLS (HMOX1, HMOX2, VDR, IL17A, IL1B, NOS1 and ADH1B). RESULTS: We found that one SNP was associated with the risk of ET in Chinese population after adjusting for age and gender: rs1143633 of IL1B (odds ratio [OR] =2.57, p = 0.003, recessive model), and the statistical result remained significant after Bonferroni correction. Then, we performed a query in Genotype-tissue Expression (GTEx), Brain eQTL Almanac (Braineac) databases and Blood expression quantitative trait loci (eQTL) browser. The significant association was only found between genotype at rs1143633 and IL1B expression level of putamen and white matter in Braineac database, which was more prominent with homozygous (GG) carriers. CONCLUSIONS: Our study firstly reported the association of IL1B polymorphism with the risk of ET in Chinese population. However, the association might only suggest a marker of IL1B SNP associated with ET instead of the casual variant. Further studies are needed to confirm our finding.