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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.
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.

3.
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
4.
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.

5.
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
6.
Seizure ; 57: 80-86, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29605618

RESUMO

PURPOSE: To describe the clinical and genetic features of a Chinese progressive myoclonus epilepsy (PME) patient related with SCARB2 mutation without renal impairment and review 27 SCARB2-related PME patients from 11 countries. METHODS: The patient was a 27-year-old man with progressive action myoclonus, ataxia, epilepsy, dysarthria and absence of cognitive deterioration. Renal functional test was normal. Electroencephalography (EEG) showed progressively slowed background activity and sporadic generalized spike-and-wave discharges. Electromyography (EMG) showed slowed motor and sensory nerve conduction velocities and distal motor latency delay accompanied by normal compound motor action potential (CMAP) and amplitudes of sensory nerve action potential (SNAP). The amplitude of cortical components of brainstem auditory-evoked potential (BAEP) was normal with slightly prolonged latencies. Generalized atrophy, ventricle enlargement and white matter degeneration was observed in brain magnetic resonance imaging (MRI). Open muscle biopsy and genetic analysis were performed. Two hundred healthy individuals were set for control. Quantitative real time PCR (qPCR), western blotting and immunofluorescence were carried out to evaluate the fate of the SCARB2 mRNA and lysosomal-membrane type 2 (LIMP2) protein level. RESULTS: One homozygous mutation in SCARB2 gene (c.1187 + 5G > T) was identified in the patient. Each of his parents carried a heterozygous variant. This mutation was not detected among the healthy controls and predicted to be damaging or disease causing by prediction tools. qPCR revealed a significantly lower level of SCARB2 mRNA in peripheral blood cell of the proband compared with his parents and healthy control individuals. Muscle biopsy showed mild variation in fiber size. Western blotting and immunofluorescence detected an extremely weak signal of LIMP2 protein from skeletal muscle of the proband. CONCLUSION: In this study, we identified a SCARB2-related PME patient with normal renal function and a novel homozygous splicing mutation. SCARB2 gene should be analyzed in patients with progressive action myoclonus, epilepsy, peripheral neuropathy, without cognitive deterioration or renal failure.


Assuntos
Glicoproteínas de Membrana Associadas ao Lisossomo/genética , Mutação , Epilepsias Mioclônicas Progressivas/genética , Receptores Depuradores/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , China , Família , Humanos , Testes de Função Renal , Masculino , Epilepsias Mioclônicas Progressivas/patologia , Epilepsias Mioclônicas Progressivas/fisiopatologia , Fenótipo
8.
Mov Disord ; 33(3): 459-467, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29356177

RESUMO

BACKGROUND: Paroxysmal kinesigenic dyskinesia is the most common type of paroxysmal dyskinesia. Approximately half of the cases of paroxysmal kinesigenic dyskinesia worldwide are attributable to proline-rich transmembrane protein 2 mutations. OBJECTIVE: The objective of this study was to investigate potential causative genes and clinical characteristics in proline-rich transmembrane protein 2-negative patients with paroxysmal kinesigenic dyskinesia. METHODS: We analyzed clinical manifestations and performed exome sequencing in a cohort of 163 proline-rich transmembrane protein 2-negative probands, followed by filtering data with a paroxysmal movement disorders gene panel. Sanger sequencing, segregation analysis, and phenotypic reevaluation were used to substantiate the findings. RESULTS: The clinical characteristics of the enrolled 163 probands were summarized. A total of 39 heterozygous variants were identified, of which 33 were classified as benign, likely benign, and uncertain significance. The remaining 6 variants (3 novel, 3 documented) were pathogenic and likely pathogenic. Of these, 3 were de novo (potassium calcium-activated channel subfamily M alpha 1, c.1534A>G; solute carrier family 2 member 1, c.418G>A; sodium voltage-gated channel alpha subunit 8, c.3640G>A) in 3 sporadic individuals, respectively. The other 3 (paroxysmal nonkinesiogenic dyskinesia protein, c.956dupA; potassium voltage-gated channel subfamily A member 1, c.765C>A; Dishevelled, Egl-10, and Pleckstrin domain containing 5, c.3311C>T) cosegregated in 3 families. All 6 cases presented with typical paroxysmal kinesigenic dyskinesia characteristics, except for the Dishevelled, Egl-10, and Pleckstrin domain containing 5 family, where the proband's mother had abnormal discharges in her temporal lobes in addition to paroxysmal kinesigenic dyskinesia episodes. CONCLUSIONS: Our findings extend the genotypic spectrum of paroxysmal kinesigenic dyskinesia and establish the associations between paroxysmal kinesigenic dyskinesia and genes classically related to other paroxysmal movement disorders. De novo variants might be a cause of sporadic paroxysmal kinesigenic dyskinesia. © 2018 International Parkinson and Movement Disorder Society.


Assuntos
Distonia/genética , Predisposição Genética para Doença/genética , Mutação/genética , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Distonia/diagnóstico , Saúde da Família , Feminino , Testes Genéticos , Transportador de Glucose Tipo 1/genética , Humanos , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Masculino , Proteínas Musculares/genética , Proteínas Repressoras/genética , Adulto Jovem
9.
Transl Neurodegener ; 6: 7, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28360996

RESUMO

BACKGROUND: Cognitive decline poses a great concern to elderly people and their families. In addition to pharmacological therapies, several varieties of nonpharmacological intervention have been developed. Most training trials proved that a well-organized task is clinically effective in cognition improvement. MAIN BODY: We will first review clinical trials of cognitive training for healthy elders, MCI and AD patients, respectively. Besides, potential neuroprotective and compensatory mechanisms in animal models of AD are discussed. Despite controversy, cognitive training has promising effect on cognitive ability. In animal model of AD, environmental enrichment showed beneficial effect for cognitive ability, as well as neuronal plasticity. Neurotrophin, neurotransmitter and neuromodulator signaling pathway were also involved in the process. Well-designed cognitive activity could benefit cognitive function, and thus life quality of patients and their families. CONCLUSION: The positive effects of cognitive activity is closely related with neural plasticity, neurotrophin, neurotransmitter and neuromodulator signaling pathway changes.

10.
Sleep Med ; 30: 71-76, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28215267

RESUMO

OBJECTIVES: To cross-sectionally explore the potential risk factors for rapid eye movement (REM) sleep behavior disorder (RBD) in a community cohort in Shanghai. METHODS: Based on the validated RBD screening questionnaire (RBDSQ), we identified individuals with probable RBD (pRBD) in 3635 community-dwelling residents (≥50 years old) from an urban community of Shanghai. Potential risk factors of pRBD, including age, sex, smoking, socioeconomic status, obesity, consumption of tea (surrogate for caffeine intake) and alcohol, medications and chronic disease status, were assessed via questionnaire. We used logistic regression to investigate the associations between these studied factors and pRBD after adjusting for age, sex and other studied factors. RESULTS: Based on the RBDSQ score ≥5, 2.70% (3.28% in men and 2.41% in women) participants were considered as pRBD. We found that lower education, presence of head injury, atrial fibrillation, hyperlipidemia, constipation, olfactory disturbance, and imbalance, use of alcoholic beverage, selective serotonin reuptake inhibitor, and benzodiazepine were associated with higher likelihood of having pRBD (P < 0.05 for all). In contrast, male sex, use of coffee or tea, smoking and other factors were not significantly association with altered risk of having pRBD. We did not find significant interaction between sex, age and these factors, in relation to pRBD risk. CONCLUSIONS: In this community-based study of older adults, we identified several potential risk factors for concurrent pRBD, including environmental factors and vascular risk factors.


Assuntos
Transtorno do Comportamento do Sono REM/epidemiologia , Adulto , Idoso , China/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
11.
BMC Neurol ; 16: 123, 2016 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-27484952

RESUMO

BACKGROUND: Our study was aimed to validate a modified RBD (REM sleep behavior disorder) single question (RBD1Q-C), study the prevalence of probable RBD (pRBD) in a rural community based on RBD1Q-C and investigate the association between pRBD and Parkinson's disease (PD). METHODS: The validation study of RBD1Q-C included 32 Chinese participants (14 idiopathic RBD patients and 18 controls). All participants underwent a polysomnogram (PSG). We then conducted a door-to-door survey to estimate the prevalence of pRBD assessed by RBD1Q-C, and its association with PD among 19614 residents who lived in Malu community of Shanghai, China. RESULTS: RBD1Q-C demonstrated a high sensitivity of 100%, a moderate specificity of 55.6%. The agreement between RBD1Q-C and PSG-based RBD diagnosis was good (k = 0.552). PPV of the RBD1Q-C was 63.6% and NPV was 100%. The prevalence of pRBD in Malu community was 4.9%. In people over 50 years old, presence of pRBD was significantly associated with increased risk of having PD (odds ratio = 2.61, 95% CI: 1.56-4.39). CONCLUSION: RBD1Q-C was shown to be a useful screening tool. Based on the RBD1Q-C, we found that pRBD was not rare in Chinese rural population and associated with odds of PD, calling for more attention from patients, caregivers and physicians.


Assuntos
Programas de Rastreamento/estatística & dados numéricos , Doença de Parkinson/epidemiologia , Transtorno do Comportamento do Sono REM/epidemiologia , Saúde da População Rural/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia/métodos , Vigilância da População , Valor Preditivo dos Testes , Prevalência , Sensibilidade e Especificidade , Adulto Jovem
12.
Front Aging Neurosci ; 8: 54, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27047371

RESUMO

In the early stage of Alzheimer disease (AD) or mild cognitive impairment (MCI), working memory (WM) deficiency is prominent and could be attributed to failure in encoding, maintenance or retrieval of information. However, evidence for a retention or retrieval deficit remains equivocal. It is also unclear what cognitive mechanism in WM is impaired in MCI or early AD. We enrolled 46 subjects from our Memory Clinics and community, with 24 amnesic MCI patients and 22 normal subjects. After neurological and cognitive assessments, they performed a classic delayed match to sample (DMS) task with simultaneous event-related potential (ERP) recorded. The ERPs in encoding and retrieval epoch during WM were analyzed separately. The latency and amplitude of every ERP component were compared between two groups, and then analyzed to explore their relationship with neuropsychological performance. Finally, the locations of maximal difference in cortex were calculated by standard low-resolution tomographic analysis. A total of five components were found: P1, N1, P2, N2, and P300. The amplitude of P2 and P300 was larger in normal subjects than in MCI patients only during retrieval, not encoding epoch, while the latency did not show statistical difference. The latency and amplitude of P1 and N1 were similar in two groups. P2 amplitude in the retrieval epoch positively correlated with memory test (auditory verbal learning test) and visual spatial score of Chinese Addenbrooke's Cognitive Examination-Revised (ACE-R), while P300 amplitude correlated with ACE-R. The activation difference in P2 time range was maximal at medial frontal gyrus. However, the difference in cortex activation during P300 time range did not show significance. The amplitude of P2 indicated deficiency in memory retrieval process, potentially due to dysfunction of central executive in WM model. Regarding the location of P2 during WM task, medial frontal plays important role in memory retrieval. The findings in the present study suggested that MCI patients have retrieval deficit, probably due to central executive based on medial frontal gyrus. Thus, it may provide new biomarker for early detection and intervention for aMCI.

13.
J Alzheimers Dis ; 49(4): 917-25, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26519443

RESUMO

BACKGROUND: China is facing a continuously rising numbers of people with cognitive impairment (CI). OBJECTIVES: To investigate the prevalence and risk factors of CI among elderly people living in rural and urban communities. METHODS: We conducted a face-to-face survey of CI on 7,900 individuals aged 50 years or older meeting inclusion criteria in the Malu (rural community, n = 4,429) and Wuliqiao (urban community, n = 3,471) communities of Shanghai. The Mini-Mental State Examination (MMSE) was used to evaluate the cognitive function. Information on demographic features and potential risk factors for CI was collected during the interview. Multivariate logistic regression was performed to identify risk factors associated with CI. RESULTS: Based on the education modified MMSE score, we identified 329 CI cases in rural community and 227 in urban community. The prevalence of CI was 7.43% in rural population and 6.54% in urban population (p = 0.13). In the urban population, risk of having CI was associated with age (OR = 1.04; 95% CI: 1.01-1.08), lack of physical activities (OR = 2.25; 95% CI: 1.11-4.57), presence of diabetes mellitus (OR = 1.79; 95% CI: 1.04-3.07), and having three or more children (OR = 2.39; 95% CI: 1.27-4.50). In contrast, factors associated with rural populations included female gender (OR = 2.03; 95% CI: 1.08-3.82), age (OR = 1.06; 95% CI: 1.03-1.08), exposure to pesticides (OR = 4.68; 95% CI: 1.27-17.21), history of encephalitis or meningitis (OR = 6.02; 95% CI: 1.92-18.85) and head trauma (OR = 1.89; 95% CI: 1.10-3.24). CONCLUSIONS: Urban rural and populations showed different risk factors for CI, suggesting that different preventive strategies in these areas should be performed.


Assuntos
Transtornos Cognitivos/epidemiologia , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Fatores de Risco , População Rural , População Urbana
14.
Curr Alzheimer Res ; 12(6): 543-52, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26238812

RESUMO

Cognitive impairment is a major concern in elderly people, and a variety of nonpharmacological therapies (NPTs) have been developed to help with cognitive decline. One of the most popular therapies is cognitive training, which includes pencil-and-paper puzzles, computerized games, or the combination of the two. Training is designed to have participants perform diverse exercises in one or more cognitive domains. Most clinical training trials indicate that well-organized tasks are clinically effective for cognitive improvement. Neural plasticity is a probable explanation for positive training effects. EEG and fMRI research show that the electrical activity and metabolism of specific brain areas are changed, and these changes are retained for a long period after training. Studies on mice to uncover the cellular and molecular changes underlying neural connectivity have found effective changes in brain networks after learning or training. Rac1 and NMDA receptors are thought to be involved in hippocampal neurogenesis, which is induced by learning. Here we review clinical trials of cognitive training, published during the last five years, and summarized some important characteristics of training tasks design. The probable role of neuronal plasticity and molecular mechanisms in training effects also are discussed. Most importantly, we discuss key ways to modifying the design of tasks based on studies we review. This review mainly identifies and discusses the reasons for positive training effects on cognition from clinical and neurophysiological perspectives. Based on the findings and their related mechanisms, further studies should design more effective and specific training tasks.


Assuntos
Envelhecimento , Ensaios Clínicos como Assunto , Terapia Cognitivo-Comportamental/métodos , Disfunção Cognitiva/reabilitação , Neurofisiologia , Doença de Alzheimer/reabilitação , Animais , Humanos , Camundongos
15.
Channels (Austin) ; 9(5): 292-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26260254

RESUMO

Myotonia congenita belongs to the group of non-dystrophic myotonia caused by mutations of CLCN1gene, which encodes human skeletal muscle chloride channel 1. It can be inherited either in autosomal dominant (Thomsen disease) or recessive (Becker disease) forms. Here we have sequenced all 23 exons and exon-intron boundaries of the CLCN1 gene, in a panel of 5 unrelated Chinese patients with myotonia congenita (2 with dominant and 3 with recessive form). In addition, detailed clinical analysis was performed in these patients to summarize their clinical characteristics in relation to their genotypes. Mutational analyses revealed 7 different point mutations. Of these, we have found 3 novel mutations including 2 missense (R47W, V229M), one splicing (IVS19+2T>C), and 4 known mutations (Y261C,G523D, M560T, G859D). Our data expand the spectrum of CLCN1 mutations and provide insights for genotype-phenotype correlations of myotonia congenita in the Chinese population.


Assuntos
Canais de Cloreto/genética , Mutação de Sentido Incorreto , Miotonia Congênita/genética , Mutação Puntual , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Processamento de RNA
16.
Aging Dis ; 6(4): 236-44, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26236545

RESUMO

We explored the potential differences in cognitive status, lipid and glucose metabolism, ApoEε4 alleles and imaging between diabetic and non-diabetic subjects. 83 subjects with normal cognitive function and 114 mild cognitive impaired patients were divided into four groups by history of diabetes. General demographics was collected from all participants followed by MRI scan, biochemical examinations and a series of neuropsychological tests. Student's t test, multiple regressions and one-way ANOVA were applied to investigate the differences between groups. Comparing diabetic patients with non-diabetic subjects in the mild cognitive impaired group, we found several decreased items in recall of three words in MMSE (p=0.020), AVLT and SCWT (p<0.050). The multiple linear regression revealed that two-hour glucose level (B= -0.255, p<0.001) and fasting C-peptide (B= -0.466, p=0.001) had negative effects on the score of MMSE. In addition, diabetic patients treated with insulin and other diabetes medication performed better in part of the AVLT (p<0.050) compared to patients with insulin treatment or oral antidiabetic medication only. Patients with metformin medication had a better memory outcome compared to patients with sulphonylurea medication in the AVLT long delay free recall (p =0.010). These findings show that patients of mild cognitive impairment with diabetes mellitus have a worse outcome in attention, information processing speed and memory compared to non-diabetic patients. Higher two-hour glucose level and C-peptide level may be risk factors for severe cognitive impairment in type-2 diabetes mellitus patients. The results of this study also suggest that medication may have effects on cognitive function.

17.
Curr Alzheimer Res ; 12(6): 572-84, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26027816

RESUMO

Although recent evidence has emerged that Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) patients show both regional brain abnormalities and topological degeneration in brain networks, our understanding of the effects of white matter fiber aberrations on brain network topology in AD and aMCI is still rudimentary. In this study, we investigated the regional volumetric aberrations and the global topological abnormalities in AD and aMCI patients. The results showed a widely distributed atrophy in both gray and white matters in the AD and aMCI groups. In particular, AD patients had weaker connectivity with long fiber length than aMCI and normal control (NC) groups, as assessed by fractional anisotropy (FA). Furthermore, the brain networks of all three groups exhibited prominent economical small-world properties. Interestingly, the topological characteristics estimated from binary brain networks showed no significant group effect, indicating a tendency of preserving an optimal topological architecture in AD and aMCI during degeneration. However, significantly longer characteristic path length was observed in the FA weighted brain networks of AD and aMCI patients, suggesting dysfunctional global integration. Moreover, the abnormality of the characteristic path length was negatively correlated with the clinical ratings of cognitive impairment. Thus, the results therefore suggested that the topological alterations in weighted brain networks of AD are induced by the loss of connectivity with long fiber lengths. Our findings provide new insights into the alterations of the brain network in AD and may indicate the predictive value of the network metrics as biomarkers of disease development.


Assuntos
Doença de Alzheimer/patologia , Encéfalo/patologia , Disfunção Cognitiva/patologia , Vias Neurais/patologia , Substância Branca/patologia , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Mapeamento Encefálico , Estudos de Casos e Controles , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade
18.
Aging Dis ; 6(3): 168-73, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26029474

RESUMO

Epidermal growth factor (EGF) is a neurotrophic factor that plays an important role in Parkinson's disease (PD). We measured plasma EGF level in PD, essential tremor (ET) and normal controls to investigate whether it changes in PD and whether it is associated with motor and non-motor symptoms of PD. 100 patients with PD, 40 patients with ET as disease control and 76 healthy persons were enrolled in the present study. Motor and non-motor symptoms were assessed by different scales. Plasma EGF levels of three groups were measured by enzyme-linked immunosorbent assay kit. Spearman test and linear logistics regression model were used to test the correlation of EGF with motor and non-motor symptoms of PD. Plasma EGF level was significantly decreased in early PD patients compared with normal control, but not in advanced PD patients. Interestingly, plasma EGF level was significantly increased in advanced PD and total PD patients compared with ET patients, but not in early PD patients. In addition, plasma EGF level was correlated with UPDRS-III scores in PD. Also plasma EGF level was correlated with UPDRS-III scores and NMS scores in early PD. Our results suggested that plasma EGF decreased in the early stage of PD and increased later on in the PD disease course. Also, plasma EGF level was increased significantly in PD compared with ET patients and correlated with motor and non-motor symptoms in early PD.

20.
Channels (Austin) ; 9(2): 82-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25839108

RESUMO

SCN4A encodes the Nav1.4 channel and mutations in SCN4A lead to different ionic channelopathies. In this study, one sporadic individual of periodic paralysis, one paramyotonia family and 200 normal healthy controls are enrolled. Genomic DNA was extracted from peripheral blood leukocytes, followed by polymerase chain reaction and DNA sequencing of candidate genes, including SCN4A and CACNA1S. As a result, heterozygous mutations c.2024G>A (R675Q) and c.1333G>A (V445M) of gene SCN4A were identified in the hypokalemic periodic paralysis patient and the paramyotonia congenita family respectively. Both mutations were not detected in healthy controls. Compared with reported cases, patients with mutation R675Q usually do not present hypokalemic periodic paralysis but hyperkalemic or normokalemic periodic paralysis. The mutation V445M was first reported in Chinese patients with nondystrophic myotonias. In addition, we carried out literature review by summarizing clinical features of the 2 mutations and establish the genotype-phenotype correlations to provide guidance for diagnosis.


Assuntos
Paralisia Periódica Hipopotassêmica/genética , Transtornos Miotônicos/genética , Canal de Sódio Disparado por Voltagem NAV1.4/genética , Adulto , Feminino , Humanos , Masculino , Mutação , Adulto Jovem
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