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1.
Mov Disord ; 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32392383

RESUMO

BACKGROUND: Paroxysmal kinesigenic dyskinesia is a spectrum of involuntary dyskinetic disorders with high clinical and genetic heterogeneity. Mutations in proline-rich transmembrane protein 2 have been identified as the major pathogenic factor. OBJECTIVES: We analyzed 600 paroxysmal kinesigenic dyskinesia patients nationwide who were identified by the China Paroxysmal Dyskinesia Collaborative Group to summarize the clinical phenotypes and genetic features of paroxysmal kinesigenic dyskinesia in China and to provide new thoughts on diagnosis and therapy. METHODS: The China Paroxysmal Dyskinesia Collaborative Group was composed of departments of neurology from 22 hospitals. Clinical manifestations and proline-rich transmembrane protein 2 screening results were recorded using unified paroxysmal kinesigenic dyskinesia registration forms. Genotype-phenotype correlation analyses were conducted in patients with and without proline-rich transmembrane protein 2 mutations. High-knee exercises were applied in partial patients as a new diagnostic test to induce attacks. RESULTS: Kinesigenic triggers, male predilection, dystonic attacks, aura, complicated forms of paroxysmal kinesigenic dyskinesia, clustering in patients with family history, and dramatic responses to antiepileptic treatment were the prominent features in this multicenter study. Clinical analysis showed that proline-rich transmembrane protein 2 mutation carriers were prone to present at a younger age and have longer attack duration, bilateral limb involvement, choreic attacks, a complicated form of paroxysmal kinesigenic dyskinesia, family history, and more forms of dyskinesia. The new high-knee-exercise test efficiently induced attacks and could assist in diagnosis. CONCLUSIONS: We propose recommendations regarding diagnostic criteria for paroxysmal kinesigenic dyskinesia based on this large clinical study of paroxysmal kinesigenic dyskinesia. The findings offered some new insights into the diagnosis and treatment of paroxysmal kinesigenic dyskinesia and might help in building standardized paroxysmal kinesigenic dyskinesia clinical evaluations and therapies. © 2020 International Parkinson and Movement Disorder Society.

2.
J Alzheimers Dis ; 75(1): 211-221, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32250297

RESUMO

BACKGROUND: Language dysfunction is a frequently reported symptom in Alzheimer's disease (AD). However, computer-assisted analysis of spontaneous speech in AD and mild cognitive impairment (MCI) is rarely used to date. OBJECTIVE: To characterize the language impairment in AD and amnestic MCI (aMCI) with computer-based automatic analysis via the "Automatic Speech Recognition (ASR) software for cognitive impairment V1.3". METHODS: A total of 64 subjects, including 20 AD patients, 20 aMCI patients, and 24 healthy controls were recruited. All subjects underwent neuropsychological tests, and spontaneous speech samples were recorded through the description of the "Cookie-Theft Picture" and then analyzed by the computerized software. Subsequently, we compared the speech parameters between the subjects and the controls. RESULTS: We identified seven spontaneous speech parameters (percentage of silence duration, average duration of phrasal segments, average duration of silence segments, number of speech segments, number of long pauses, ratio of hesitation/speech counts and ratio of short pause/speech counts) demonstrating significant differences between the three groups (p < 0.05). All seven speech parameters significantly correlated with cognitive performance, with average duration of silence segments demonstrating the best correlation to cognitive performance on stepwise multiple linear regression analysis. CONCLUSION: Computer-assisted automated analysis of speech/silence segments demonstrated the potential to reflect the intrinsic linguistic impairment associated with MCI and AD. It has a promising prospect in the early detection of AD and assessment of disease severity.

3.
BMC Neurol ; 20(1): 114, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228519

RESUMO

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.

4.
Ann Clin Transl Neurol ; 7(2): 200-209, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32023010

RESUMO

OBJECTIVE: To describe the clinical and genetic features of two patients with different phenotypes due to various Dynactin 1 (DCTN1) gene mutations and further explore the phenotype-genotype relationship. METHODS: Patient 1 is a 23-year-old man with congenital foot deformity and life-long distal muscle weakness and atrophy. Patient 2 is a 48-year-old woman with adult-onset progressive weakness, lower limbs atrophy, and pyramid bundle signs. Electrophysiology test showed normal nerve conduction velocity of both patients and neurogenic changes in needle electromyography. Open sural nerve biopsy for Patient 1 showed slight loss of myelinated nerve fibers. Both patients were performed with whole-exome sequencing followed by functional study of identified variants. RESULTS: Two mutations in DCTN1 gene were identified in Patient 1 (c.626dupC) and Patient 2 (c.3823C>T), respectively. In vitro, the wild type mostly located in cytoplasm and colocalized with α-tubulin. However, c.626dupC tended to be trapped into nuclear and the c.3823C>T formed cytoplasmic aggregates, both losing colocalization with α-tubulin. Western blotting showed a truncated mutant with less molecular weight of c.626dupC was expressed. INTERPRETATION: We identify two novel DCTN1 mutations causing different phenotypes: (1) early-onset distal hereditary motor neuropathy plus congenital foot malformation and (2) amyotrophic lateral sclerosis, respectively. We provide the initial evidence that foot developmental deficiency probably arises from subcellular localizing abnormality of Dynactin 1, revealing DCTN1-related spectrum is still expanding.

5.
Transl Neurodegener ; 8: 32, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827782

RESUMO

Background: CSF1R-related leukoencephalopathy, also known as hereditary diffuse leukoencephalopathy with spheroids (HDLS), is a rare white-matter encephalopathy characterized by motor and neuropsychiatric symptoms due to colony-stimulating factor 1 receptor (CSF1R) gene mutation. Few of CSF1R mutations have been functionally testified and the pathogenesis remains unknown. Methods: In order to investigate clinical and pathological characteristics of patients with CSF1R-related leukoencephalopathy and explore the potential impact of CSF1R mutations, we analyzed clinical manifestations of 15 patients from 10 unrelated families and performed brain biopsy in 2 cases. Next generation sequencing was conducted for 10 probands to confirm the diagnosis. Sanger sequencing, segregation analysis and phenotypic reevaluation were utilized to substantiate findings. Functional examination of identified mutations was further explored. Results: Clinical and neuroimaging characteristics were summarized. The average age at onset was 35.9 ± 6.4 years (range 24-46 years old). Younger age of onset was observed in female than male (34.2 vs. 39.2 years). The most common initial symptoms were speech dysfunction, cognitive decline and parkinsonian symptoms. One patient also had marked peripheral neuropathy. Brain biopsy of two cases showed typical pathological changes, including myelin loss, axonal spheroids, phosphorylated neurofilament and activated macrophages. Electron microscopy disclosed increased mitochondrial vacuolation and disorganized neurofilaments in ballooned axons. A total of 7 pathogenic variants (4 novel, 3 documented) were identified with autophosphorylation deficiency, among which c.2342C > T remained partial function of autophosphorylation. Western blotting disclosed the significantly lower level of c.2026C > T (p.R676*) than wild type. The level of microtubule associated protein 1 light chain 3-II (LC3-II), a classical marker of autophagy, was significantly lower in mutants expressed cells than wild type group by western blotting and immunofluorescence staining. Conclusions: Our findings support the loss-of-function and haploinsufficiency hypothesis in pathogenesis. Autophagy abnormality may play a role in the disease. Repairing or promoting the phosphorylation level of mutant CSF1R may shed light on therapeutic targets in the future. However, whether peripheral polyneuropathy potentially belongs to CSF1R-related spectrum deserves further study with longer follow-up and more patients enrolled. Trial registration: ChiCTR, ChiCTR1800015295. Registered 21 March 2018.

6.
Ann Clin Transl Neurol ; 6(6): 1062-1071, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31211170

RESUMO

Objective: GDP-mannose pyrophosphorylase B (GMPPB) related phenotype spectrum ranges widely from congenital myasthenic syndrome (CMS), limb-girdle muscular dystrophy type 2T (LGMD 2T) to severe congenital muscle-eye-brain syndrome. Our study investigates the clinicopathologic features of a patient with novel GMPPB mutations and explores the pathogenetic mechanism. Methods: The patient was a 22-year-old woman with chronic proximal limb weakness for 9 years without cognitive deterioration. Weakness became worse after fatigue. Elevated serum creatine kinase and decrements on repetitive nerve stimulation test were recorded. MRI showed fatty infiltration in muscles of lower limbs and shoulder girdle on T1 sequence. Open muscle biopsy and genetic analysis were performed. Results: Muscle biopsy showed myogenic changes. Two missense mutations in GMPPB gene (c.803T>C and c.1060G>A) were identified in the patient. Western blotting and immunostaining showed GMPPB and α-dystroglycan deficiency in the patient's muscle. In vitro, mutant GMPPB forming cytoplasmic aggregates completely colocalized with microtubule-associated protein 1 light chain 3-II (LC3-II), a classical marker of autophagosome. Degradation of GMPPB was accompanied by an upregulation of LC3-II, which could be restored by lysosomal inhibitor leupeptin. Interpretation: We identified two novel GMPPB mutations causing overlap phenotype between LGMD 2T and CMS. We provided the initial evidence that mutant GMPPB colocalizes with autophagosome at subcellular level. GMPPB mutants degraded by autophagy-lysosome pathway is associated with LGMD 2T. This study shed the light into the enzyme replacement which could become one of the therapeutic targets in the future study.

7.
Neurobiol Aging ; 77: 154-157, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30822634

RESUMO

Causative mutations in the genes encoding amyloid precursor protein (APP), presenilin 1 (PSEN1), or presenilin 2 (PSEN2) account for a majority of cases of familial Alzheimer disease (FAD) inherited in an autosomal-dominant pattern. For the sake of characterizing mutations, index patients from 148 families with FAD were enrolled from mainland China. Sanger sequencing of the genes APP, PSEN1, and PSEN2 was performed to characterize the mutation spectrum of the Chinese population. Thirteen of 148 (8.8%) individuals had possible pathogenic APP, PSEN1, or PSEN2 variants, including 2 (15.4%) APP variants, 8 (61.5%) PSEN1 variants, and 3 (23.1%) PSEN2 variants. PSEN1 variants represented the largest proportion in Chinese FAD, and PSEN2 variants are responsible for late-onset FAD in China. Analysis of genetic-clinical correlations permitted the conclusion that FAD phenotypes were mainly influenced by specific genetic defects.


Assuntos
Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Mutação , Presenilina-1/genética , Presenilina-2/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Genes Dominantes , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo
8.
Neuroimage Clin ; 22: 101691, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30708349

RESUMO

BACKGROUND: Computerized multi-model training has been widely studied for its effect on delaying cognitive decline. In this study, we designed the first Chinese-version computer-based multi-model cognitive training for mild cognitive impairment (MCI) patients. Neuropsychological effects and neural activity changes assessed by functional MRI were both evaluated. METHOD: MCI patients in the training group were asked to take training 3-4 times per week for 6 months. Neuropsychological and resting-state fMRI assessment were performed at baseline and at 6 months. Patients in both groups were continuously followed up for another 12 months and assessed by neuropsychological tests again. RESULTS: 78 patients in the training group and 63 patients in the control group accomplished 6-month follow-up. Training group improved 0.23 standard deviation (SD) of mini-mental state examination, while control group had 0.5 SD decline. Addenbrooke's cognitive examination-revised scores in attention (p = 0.002) and memory (p = 0.006), as well as stroop color-word test interference index (p = 0.038) and complex figure test-copy score (p = 0.035) were also in favor of the training effect. Difference between the changes of two groups after training was not statistically significant. The fMRI showed increased regional activity at bilateral temporal poles, insular cortices and hippocampus. However, difference between the changes of two groups after another 12 months was not statistically significant. CONCLUSIONS: Multi-model cognitive training help MCI patients to gained cognition benefit, especially in memory, attention and executive function. Functional neuroimaging provided consistent neural activation evidence. Nevertheless, after one-year follow up after last training, training effects were not significant. The study provided new evidence of beneficial effect of multi-model cognitive training.


Assuntos
Córtex Cerebral/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/reabilitação , Remediação Cognitiva/métodos , Terapia Assistida por Computador/métodos , Idoso , Córtex Cerebral/diagnóstico por imagem , China , Disfunção Cognitiva/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Resultado do Tratamento
9.
Neuromuscul Disord ; 29(4): 282-289, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30737079

RESUMO

The congenital disorders of glycosylation are a group of clinically and biochemically heterogeneous diseases characterized by multisystem involvement due to glycosylation defect of protein and lipid. Here we report a 49-year-old man with exercise-induced fatigue and pain of muscle, tachypnea, cleft palate and bifid uvula. Exercise induced elevation of serum creatine kinase (CK), ammonia and lactic acid was recorded. The abnormal levels of myoglobin, CK-MB and LDH as well as S-T elevation in electrocardiogram were observed in repeated hospitalization recordings. Electromyography showed myopathic damage. Repetitive nerve stimulation test of low rates showed decrement in the left deltoid muscle. He was identified with a novel homozygous frameshift variant in Phosphoglucomutase type 1 gene (c.405delT p.N135Kfs*9) by whole exome sequencing. Muscle biopsy exhibited minimal variation in fiber size without abnormal glycogen accumulation. Compared with controls', the patient's sample showed no signal at ∼61 kDa using N- or C-terminus antibody of Phosphoglucomutase type 1 in western blotting. A signal at ∼20 kDa was detected in patient using N-terminus antibody. Immunofluorescence revealed trace expression of C-terminus and a much lower expression of N-terminus on the sarcolemma than normal. Our findings indicate that c.405delT encodes a truncated protein with abnormal distribution and expression in skeletal muscle. In conclusion, genes associated with congenital disorders of glycosylation should be analyzed in patients with maxillofacial dysplasia, exertional weakness, cardiac involvement and exercise-induced-ammoniemia, without glycogen storage in skeletal muscle.

10.
Front Aging Neurosci ; 11: 4, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30760995

RESUMO

[This corrects the article DOI: 10.3389/fnagi.2018.00156.].

11.
Front Aging Neurosci ; 11: 18, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30804778

RESUMO

Background: Hyposmia is one of the most important clinical markers of Parkinson's disease (PD) with a prevalence ranging from 50 to 96% of PD patients. A significant association was found between hyposmia and cognitive impairment of PD. However, there were no reports of event-related potentials (ERP) performance in PD patients with and without hyposmia for cognitive functions assessment. Purpose: The aim of our study was to compare ERP performance and its association with cognitive domains between PD with and without hyposmia. Methods: Olfactory functions were assessed by Sniffin' Sticks test-16 (SS-16). Twenty-four subjects were included in PD with hyposmia group and nineteen were in PD without hyposmia group. ERP measures were recorded during a delayed match to sample (DMS) task with Chinese characters. The parameters of ERP components including N1, N2, P1, P2, and P3 in retrieval epoch were compared between the two groups and the correlation between ERP results and MOCA item score was also analyzed. Results: No significant difference was found in ERP performance between PD with and without hyposmia. Among all participants, N1 latency was significantly negatively related to visuospatial-executive item score of Montreal Cognitive Assessment (MOCA) (r s = -0.381, P = 0.012) and P1 amplitude was positively associated with language item score of MOCA (r s = 0.302, P = 0.049). Within the normosmic group, a significant association was found between N1 latency and visuospatial-executive item score (r s = -0.619, P = 0.005) and there was also a correlation between language score and P1 amplitude (r s = 0.537, P = 0.018). In the hyposmic group, only a significant correlation was found between N1 latency and clock drawing test performance (r s = -0.413, P = 0.045) rather than visuospatial-executive item score. Furthermore, SS-16 score was not found to be significantly associated with either visuospatial-executive or language item score of MOCA. Conclusion: No significant difference was found in ERP components between PD with and without hyposmia. N1 latency and P1 amplitude were respectively associated with visuospatial-executive and language functions in the normosmic group while in the hyposmic group, only a significant correlation was found between N1 latency and clock drawing test performance rather than visuospatial-executive item score in MOCA.

12.
Artigo em Inglês | MEDLINE | ID: mdl-30684527

RESUMO

BACKGROUND: Transient receptor potential canonical (TRPC) 6 inhibits Aß in Alzheimer's disease (AD) mouse brain and improves the behavioral performance. AIMS: To evaluate the association of TRPC6 expression in peripheral leucocytes from AD and mild cognitive impairment (MCI) patients and to explore its potential value in early diagnosis of AD. METHODS: TRPC6 mRNA levels in peripheral leucocytes were detected by quantitative real-time PCR. The Spearman correlation test was used to ascertain the associations between TRPC6 and the scores of MMSE, ADL, CSDD, CDR. The Receiver Operating Characteristic (ROC) curve was drawn to evaluate the diagnostic potential of TRPC6 for AD and MCI. RESULTS: There were 108 CE, 136 MCI, 164 Con and 60 PD in the study. The expression of TRPC6 mRNA level in peripheral leucocytes was significantly lower: 1) in patients with AD and MCI compared to Con; 2) in AD compared to MCI; 3) in hospitalized AD compared to AD from communities. There was a significantly positive correlation between TRPC6 mRNA and MMSE score (p = .001, R = 0.327). Significantly inverse correlations were found between TRPC6 and CDR score (p < 0.001, R = -0.303) as well as between TRPC6 and ADL score (p = .001, R = -0.342) for all AD. The area under curve of ROC was 0.881 for the classification of AD, and 0.706 for the classification of MCI, respectively. CONCLUSION: TRPC6 expression is inversely correlated with cognitive performance of AD. TRPC6 in peripheral leucocytes may be a potential biomarker for the diagnosis of AD.


Assuntos
Doença de Alzheimer/metabolismo , Disfunção Cognitiva/metabolismo , Canal de Cátion TRPC6/biossíntese , Idoso , Estudos de Casos e Controles , Diagnóstico Precoce , Feminino , Hospitalização , Humanos , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/metabolismo , Escalas de Graduação Psiquiátrica/estatística & dados numéricos
14.
Clin Neurophysiol ; 129(11): 2435-2441, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30293034

RESUMO

OBJECTIVE: To unravel if there was muscular ion channel dysfunction in paroxysmal kinesigenic dyskinesia (PKD) patients using the exercises tests (ET). METHODS: Sixty PKD patients including 28 PRRT2 mutations carriers were enrolled in this study, as well as 19 hypokalaemic periodic paralysis (HypoPP) patients as the positive controls and 45 healthy subjects as the negative controls. ET including long exercise test (LET) and short exercise test (SET) was performed in the corresponding subjects. RESULTS: In the LET, both the overall PKD patients and HypoPP patients had greater CMAP amplitude and area increments during exercise than healthy controls. At most 25% of PKD patients were identified from the normality with greater amplitude increment than the area. On the contrary, 50% of HypoPP patients were differentiated with greater area increment than the amplitude. More percentage of PRRT2- patients than PRRT2+ patients had abnormal average amplitude increment. Unexpectedly, five PKD patients had abnormal maximum CMAP amplitude decrements after exercise in the LET, and one had abnormal maximum immediate amplitude decrement in the SET. CONCLUSIONS: Distinct ET manifestations were found in PKD patients compared to normal controls and HypoPP patients. SIGNIFICANCE: Abnormal muscle membrane excitability might be involved in the mechanisms responsible for PKD.


Assuntos
Distonia/fisiopatologia , Teste de Esforço/métodos , Músculo Esquelético/fisiopatologia , Potenciais de Ação , Adolescente , Adulto , Criança , Distonia/diagnóstico , Distonia/genética , Feminino , Humanos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Músculo Esquelético/inervação , Proteínas do Tecido Nervoso/genética , Nervo Ulnar/fisiopatologia
15.
Transl Neurodegener ; 7: 15, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30062008

RESUMO

Background: The differential diagnosis of Parkinson's disease (PD) and multiple system atrophy (MSA) remains a challenge, especially in the early stage. Here, we assessed the value of transcranial sonography (TCS) to discriminate non-tremor dominant (non-TD) PD from MSA with predominant parkinsonism (MSA-P). Methods: Eighty-six MSA-P patients and 147 age and gender-matched non-TD PD patients who had appropriate temporal acoustic bone windows were included in this study. All the patients were followed up for at least 2 years to confirm the initial diagnosis. Patients with at least one substantia nigra (SN) echogenic size ≥18 mm2 were classified as hyperechogenic, those with at least one SN echogenic size ≥25 mm2 was defined as markedly hyperechogenic. Results: The frequency of SN hyperechogenicity in non-TD PD patients was significantly higher than that in MSA-P patients (74.1% vs. 38.4%, p <  0.001). SN hyperechogenicity discriminated non-TD PD from MSA-P with sensitivity of 74.1%, specificity of 61.6%, and positive predictive value of 76.8%. If marked SN hyperechogenicity was used as the cutoff value (≥ 25 mm2), the sensitivity decreased to 46.3%, but the specificity and positive predictive value increased to 80.2 and 80.0%. Additionally, in those patients with SN hyperechogenicity, positive correlation between SN hyperechogenicity area and disease duration was found in non-TD PD rather than in MSA-P patients. In this context, among early-stage patients with disease duration ≤3 years, the sensitivity, specificity and positive predictive value of SN hyperechogenicity further declined to 69.8%, 52.2%, and 66.7%, respectively. Conclusions: TCS could help discriminate non-TD PD from MSA-P in a certain extent, but the limitation was also obvious with relatively low specificity, especially in the early stage.

16.
BMC Neurol ; 18(1): 122, 2018 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-30134845

RESUMO

BACKGROUND: Chinese guidelines for management of Parkinson's disease (PD) have been issued and updated regularly since 2006. We undertook a cross-sectional survey to evaluate the impact of the latest edition (2014) on current approaches to the management of PD based on previous pilot works. METHODS: Seven hundred and seventeen participants, divided into 3 groups (GPs, Neurologists, and Specialists), recruited from 138 randomly chosen hospitals from 30 cities across China, participated by completing the questionnaire describing their current approaches before and after the guidelines were issued. RESULTS: Considerable discrepancies in management were apparent across the three categories, with different selection of first-choice medication for PD patients. There were also variations in management of concurrent psychiatric symptoms and dementia. Notably, over 50% of participants reported improvements in PD recognition and management by following the guidelines. CONCLUSIONS: The increasing use of Chinese clinical practice guidelines for PD management is having a positive impact on the optimization of care, which in turn offers important economic benefits.


Assuntos
Hospitais/estatística & dados numéricos , Doença de Parkinson , Padrões de Prática Médica/estatística & dados numéricos , China/epidemiologia , Estudos Transversais , Humanos , Neurologistas/estatística & dados numéricos , Doença de Parkinson/epidemiologia , Doença de Parkinson/terapia , Médicos/estatística & dados numéricos , Inquéritos e Questionários
17.
Parkinsonism Relat Disord ; 57: 72-76, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30119933

RESUMO

INTRODUCTION: Glucocerebrosidase (GBA) mutations and leucine-rich repeat kinase 2 (LRRK2) variants are the most common genetic risk factors for late-onset Parkinson's disease (PD). In this study, we aimed to investigate the differences in pre-diagnostic symptoms of PD associated with the variants. METHODS: The participants were recruited from 24 centers across China and genotyped for LRRK2 G2385R and R1628P variants and GBA L444P mutation. Participants were surveyed with structural questionnaires for history of environmental exposure and living habits and interviewed to collect the time at onset of each symptoms before diagnosis. We compared the cumulative prevalence and manifestation pattern of symptoms between groups using multiple logistic regression, adjusting age and gender. RESULTS: Total 1799 PD patients were recruited, including 226 patients with LRRK2 G2385R or R1628P variant, 44 with GBA L444P mutation, three with both LRRK2 and GBA mutation, and 1526 idiopathic patients. The cumulative prevalence of non-motor and typical motor symptoms did not differ between groups before diagnosis (P > 0.05). The manifestation sequences of non-motor symptoms were indistinguishable between the LRRK2-carriers, GBA-carriers, and idiopathic PD subjects, and followed the sequence of constipation, hyposmia, sleep disorders, anxiety and depression, sexual dysfunction, urinary incontinency, dizziness and cognition. Slightly higher prevalence of hypomimia and micrographia were detected in the GBA-carriers. CONCLUSIONS: The prevalence of pre-diagnostic symptoms is almost indistinguishable between the LRRK2-carriers, GBA-carriers, and idiopathic PD before diagnosis; the sequence of the manifestation of non-motor symptoms largely conforms to the Braak stage for both genetic-related and idiopathic late-onset PD.


Assuntos
Doença de Parkinson/complicações , Doença de Parkinson/genética , Sintomas Prodrômicos , Idoso , Feminino , Glucosilceramidase/genética , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos
18.
Front Aging Neurosci ; 10: 156, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29881345

RESUMO

Emerging evidence suggests that the microbiota present in feces plays a role in Parkinson's disease (PD). However, the alterations of the microbiome in the blood of PD patients remain unknown. To test this hypothesis, we conducted this case-control study to explore the microbiota compositions in the blood of Chinese PD patients. Microbiota communities in the blood of 45 patients and their healthy spouses were investigated using high-throughput Illumina HiSeq sequencing targeting the V3-V4 region of 16S ribosomal RNA (rRNA) gene. The relationships between the microbiota in the blood and PD clinical characteristics were analyzed. No difference was detected in the structure and richness between PD patients and healthy controls. The following genera were enriched in the blood of PD patients: Isoptericola, Cloacibacterium, Enhydrobacter and Microbacterium; whereas genus Limnobacter was enriched in the healthy controls after adjusting for age, gender, body mass index (BMI) and constipation. Additionally, the findings regarding these genera were validated in another independent group of 58 PD patients and 57 healthy controls using real-time PCR targeting genus-specific 16S rRNA genes. Furthermore, not only the genera Cloacibacterium and Isoptericola (which were identified as enriched in PD patients) but also the genera Paludibacter and Saccharofermentans were positively associated with disease duration. Some specific genera in the blood were related to mood disorders. We believe this is the first report to provide direct evidence to support the hypothesis that the identified microbiota in the blood are associated with PD. Additionally, some microbiota in the blood are closely associated with the clinical characteristics of PD. Elucidating these differences in blood microbiomes will provide a foundation to improve our understanding of the role of microbiota in the pathogenesis of PD.

20.
Chin Med J (Engl) ; 131(8): 894-898, 2018 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-29664047

RESUMO

Background: Memory complaint is common in the elderly. Recently, it was shown that self-report memory complaint was predictive of cognitive decline. This study aimed to investigate the predictive value of the source of memory complaints on the risk of cognitive impairment and cognitive decline in a community-based cohort. Methods: Data on memory complaints and cognitive function were collected among 1840 Chinese participants (aged ≥55 years old) in an urban community at baseline interview and 5-year follow-up. Incident cognitive impairment was identified based on education-adjusted Mini-Mental State Examination score. Logistic regression model was used to estimate the association between the source of memory complaints and risk of cognitive impairment conversion and cognitive decline, after adjusting for covariates. Results: A total of 1840 participants were included into this study including 1713 normal participants and 127 cognitive impairment participants in 2009. Among 1713 normal participants in 2009, 130 participants were converted to cognitive impairment after 5 years of follow-up. In 2014, 606 participants were identified as cognitive decline. Both self- and informant-reported memory complaints were associated with an increased risk of cognitive impairment (odds ratio [OR] = 1.60, 95% confidence interval [CI]: 1.04-2.48) and cognitive decline (OR = 1.30, 95% CI: 1.01-1.68). Furthermore, this association was more significant in males (OR = 2.10, 95% CI: 1.04-4.24 for cognitive impairment and OR = 1.87, 95% CI: 1.20-2.99 for cognitive decline) and in higher education level (OR = 1.79, 95% CI: 1.02-3.15 for cognitive impairment and OR = 1.40, 95% CI: 1.02-1.91 for cognitive decline). Conclusions: Both self- and informant-reported memory complaints were associated with an increased risk of cognitive impairment conversion and cognitive decline, especially in persons with male gender and high educational background.


Assuntos
Cognição/fisiologia , Disfunção Cognitiva/fisiopatologia , Memória/fisiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Razão de Chances
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