Ku-chou Chang

Apolipoprotein E , angiotensin-converting enzyme and kallikrein gene polymorphisms and the risk of Alzheimer’s disease and vascular dementia

Summary.Lipoproteins and vascular factors may play roles in the development of Alzheimer’s disease (AD) and/or vascular dementia (VaD). In this study, odd ratios (ORs) and 95% confidence intervals (CIs) for apolipoprotein E (APOE), angiotensin-converting enzyme (ACE), and kallikrein (KLK1) polymorphisms were computed to test their association with the disease by a case-control study. The risk of AD was significantly increased for individuals with APOE ɛ4 allele (OR = 3.73, 95% CI = 2.38–5.98). The risk of AD was also significant for people with ACE DD genotype, D allele, or T-D haplotype [OR (95% CI) = 4.29 (1.96–10.23), 1.90 (1.35–2.70), or 2.91 (1.71–5.10), respectively]. The above association between ACE-VaD was also strong (p = 0.0012, 0.0050, 0.0007, respectively). Reporter constructs containing the −240 A or T allele displayed similar transcriptional activity in both HEK-293 and IMR-32 cells. Thus, another putative pathogenic marker that is linked with the Alu D allele might affect the risk of AD and VaD in Taiwan.

α-Synuclein promoter RsaI T-to-C polymorphism and the risk of Parkinson’s disease

Summary.Increased α-synuclein expression may be involved in the pathogenesis of Parkinson’s disease (PD). We investigated the association of Rep1 microsatellite and RsaI T-to-C substitution in the α-synuclein promoter region with the risk of PD by a case-control study. The RsaI C/C genotype and C allele were found less frequently in PD patients than in controls. A reduced risk of the Rep1-RsaI 0-C haplotype (OR = 0.57, 95% CI = 0.36–0.90) with PD was evident. The quantitative real-time PCR study showed that the α-synuclein mRNA expression was increased (although not significantly) in PD patients with RsaI T/T genotype or Rep1-RsaI 0-T haplotype as compared to T/C genotype or 0-C haplotype. Reporter constructs containing the RsaI C allele drove significantly lower transcriptional activity compared with the RsaI T allele in both IMR32 and 293 cells. The findings suggest that the RsaI T-to-C substitution may have a functional relevance to the susceptibility to PD.

Bilateral robotic priming before task-oriented approach in subacute stroke rehabilitation: a pilot randomized controlled trial:

Objectives: To investigate the treatment effects of bilateral robotic priming combined with the task-oriented approach on motor impairment, disability, daily function, and quality of life in patients with subacute stroke. Design: A randomized controlled trial. Setting: Occupational therapy clinics in medical centers. Subjects: Thirty-one subacute stroke patients were recruited. Interventions: Participants were randomly assigned to receive bilateral priming combined with the task-oriented approach (i.e., primed group) or to the task-oriented approach alone (i.e., unprimed group) for 90 minutes/day, 5 days/week for 4 weeks. The primed group began with the bilateral priming technique by using a bimanual robot-aided device. Main measures: Motor impairments were assessed by the Fugal-Meyer Assessment, grip strength, and the Box and Block Test. Disability and daily function were measured by the modified Rankin Scale, the Functional Independence Measure, and actigraphy. Quality of life was examined by the Stroke Impact Scale. Results: The primed and unprimed groups improved significantly on most outcomes over time. The primed group demonstrated significantly better improvement on the Stroke Impact Scale strength subscale (p = 0.012) and a trend for greater improvement on the modified Rankin Scale (p = 0.065) than the unprimed group. Conclusion: Bilateral priming combined with the task-oriented approach elicited more improvements in self-reported strength and disability degrees than the task-oriented approach by itself. Further large-scale research with at least 31 participants in each intervention group is suggested to confirm the study findings.

Evolving methods to combine cognitive and physical training for individuals with mild cognitive impairment: study protocol for a randomized controlled study

BackgroundNonpharmacologic interventions, such as cognitive training or physical exercise, are effective in improving cognitive functions for older adults with mild cognitive impairment (MCI). Some researchers have proposed that combining physical exercise with cognitive training may augment the benefits of cognition. However, strong evidence is lacking regarding whether a combined therapy is superior to a single type of training for older adults with MCI. Moreover, which combination approach – combining physical exercise with cognitive training sequentially or simultaneously – is more advantageous for cognitive improvement is not yet clear. This proposed study is designed to clarify these questions.Methods/designThis study is a single-blinded, multicenter, randomized controlled trial. Eighty individuals with MCI will be recruited and randomly assigned to cognitive training (COG), physical exercise training (PE), sequential training (SEQ), and dual-task training (DUAL) groups. The intervention programs will be 90 min/day, 2–3 days/week, for a total of 36 training sessions. The participants in the SEQ group will first perform 45 min of physical exercise followed by 45 min of cognitive training, whereas those in the DUAL group will perform physical exercise and cognitive training simultaneously. Participants will be assessed at baseline, after the intervention, and at 6-month follow-up. The primary cognitive outcome tests will include the Montreal Cognitive Assessment and the color-naming Stroop test. Other outcomes will include assessments that evaluate the cognitive, physical, and daily functions of older adults with MCI.DiscussionThe results of this proposed study will provide important information regarding the feasibility and intervention effects of combining physical exercise and cognitive training for older individuals with MCI.Trial registrationClinicalTrials.gov Identifier: NCT02512627, registered on 20 July 2015.

Constraint-induced movement therapy translated into practice

Constraint-induced movement therapy (CIMT) is the massed task practice of the aff ected limb with shaping techniques and constraint of the unaff ected limb. CIMT and modifi ed CIMT are the most empirically supported approaches to rehabilitation of the upper limbs after stroke. CIMT is a successful example of translating fi ndings from basic research (from animal studies), to human clinical research (including phase 1–3 clinical trials) and practicebased research (phase 3 randomised trials). In one study of 222 patients with stroke-related upper limb dysfunction, the eff ect of CIMT given before or after routine therapy was compared with standard care; however, without data from clinical practice, the assessment of CIMT or modifi ed CIMT is arguably a conceptual investigation that will not benefi t patients who receive regular therapy at clinics. In The Lancet Neurology, Anne Barzel and colleagues now report used for the fi rst time in ALS in a study investigating lithium carbonate, in response to a report describing the potential benefi ts with lithium that triggered a frenzy of hope in the ALS community. The use of historical controls was well justifi ed in the case of lithium because various randomised controlled trials with lithium were already on the horizon. Yet nearly everyone agrees that studies with historical controls are useful only for probing of possibilities, and that any possible effi cacy shown should be followed by appropriate randomised controlled trials. Because the ALS community has already accumulated a large amount of data, meaningful historical control-based studies might become a viable option in the future, but how to select historical controls in each trial is still an issue of fundamental importance. Although the DiPALS investigators fully discuss possible reasons for poor outcomes with non-invasive ventilation and diaphragm pacing in their report, the mechanisms of why this happened could have been investigated with use of periodical nocturnal pulse oximetry and, in selected patients, polysomnograms could have been obtained. This information would have helped us learn how to manage non-invasive ventilation in the future. Our experience with diaphragm pacing raises several important questions of how to undertake ALS clinical trials properly and from early stages. There is a strong need for new international guidelines for clinical trials of ALS, which would detail how to undertake more eff ective and effi cient clinical trials in the future, especially because the current guidelines are already 16 years old. Hiroshi Mitsumoto Eleanor and Lou Gehrig MDA/ALS Center, Department of Neurology, Columbia University Medical Center, New York, NY 10032 USA hm264@columbia.edu

Effects of home-based versus clinic-based rehabilitation combining mirror therapy and task-specific training for patients with stroke: a randomized crossover trial

OBJECTIVE We investigated the treatment effects of a home-based rehabilitation program compared with clinic-based rehabilitation in patients with stroke. DESIGN A single-blinded, 2-sequence, 2-period, crossover-designed study. SETTING Rehabilitation clinics and participants home environment. PARTICIPANTS Individuals with disabilities poststroke. INTERVENTIONS During each intervention period, each participant received 12 training sessions, with a 4-week washout phase between the 2 periods. Participants were randomly allocated to home-based rehabilitation first or clinic-based rehabilitation first. Intervention protocols included mirror therapy and task-specific training. MAIN OUTCOME MEASURES Outcome measures were selected based on the International Classification of Functioning, Disability and Health. Outcomes of impairment level were the Fugl-Meyer Assessment, Box and Block Test, and Revised Nottingham Sensory Assessment. Outcomes of activity and participation levels included the Motor Activity Log, 10-meter walk test, sit-to-stand test, Canadian Occupational Performance Measure, and EuroQoL-5D Questionnaire. RESULTS Pretest analyses showed no significant evidence of carryover effect. Home-based rehabilitation resulted in significantly greater improvements on the Motor Activity Log amount of use subscale (P=.01) and the sit-to-stand test (P=.03) than clinic-based rehabilitation. The clinic-based rehabilitation group had better benefits on the health index measured by the EuroQoL-5D Questionnaire (P=.02) than the home-based rehabilitation group. Differences between the 2 groups on the other outcomes were not statistically significant. CONCLUSIONS The home-based and clinic-based rehabilitation groups had comparable benefits in the outcomes of impairment level but showed differential effects in the outcomes of activity and participation levels.

Effects and mechanism of the HECT study (hybrid exercise-cognitive trainings) in mild ischemic stroke with cognitive decline: fMRI for brain plasticity, biomarker and behavioral analysis

Purpose Cognitive decline after stroke is highly associated with functional disability. Empirical evidence shows that exercise combined cognitive training may induce neuroplastic changes that modulate cognitive function. However, it is unclear whether hybridized exercise-cognitive training can facilitate cortical activity and physiological outcome measures and further influence on the cognitive function after stroke. This study will investigate the effects of two hybridized exercise-cognitive trainings on brain plasticity, physiological biomarkers and behavioral outcomes in stroke survivors with cognitive decline. Methods and significance This study is a single-blind randomized controlled trial. A target sample size of 75 participants is needed to obtain a statistical power of 95% with a significance level of 5%. Stroke survivors with mild cognitive decline will be stratified by Mini-Mental State Examination scores and then randomized 1:1:1 to sequential exercise-cognitive training, dual-task exercise-cognitive training or control groups. All groups will undergo training 60 min/day, 3 days/week, for a total of 12 weeks. The primary outcome is the resting-state functional connectivity and neural activation in the frontal, parietal and occipital lobes in functional magnetic resonance imaging. Secondary outcomes include physiological biomarkers, cognitive functions, physical function, daily functions and quality of life. This study may differentiate the effects of two hybridized trainings on cognitive function and health-related conditions and detect appropriate neurological and physiological indices to predict training effects. This study capitalizes on the groundwork for a non-pharmacological intervention of cognitive decline after stroke.

Biomarker discovery for polyglutamine-mediated SCA17 using transiently transfected 293 and lymphoblastoid cells with TBP expansion

cells (FS) (Inoue et al., 1999). During early postnatal development, rat anterior pituitary cells re-accommodate in the gland tissue, implicating intense migration activity. We have shown that cultured infantile pituitary cells migrate preferentially over collagen type I/III, and the epidermal growth factor (EGF) stimulates this behaviour. Moreover, EGF stimulation induces an increase in cell association (González et al., 2004) and cell spreading (Toral et al., 2003). The aim of the present study was to investigate more about the migration and association behaviour of SC and FS using a vertical diffusion chamber. Aliquots of 3 × 10 rat infantile pituitary cells were placed in the upper compartment without or with EGF (50 ng/ml) in a defined culture medium. Cells were allow migrating to the lower compartment through the 12 m pore size and settled on a cover glass coated with collagen I/III. After 48 h, the migrated cells were fixed and stained with toluidine blue or assay for fluorescent-immunocytochemistry for S-100 , identifying FS, chromogranin A, identifying SC, nucleus with To-Pro-3iodide and F-actin with TRICT-phalloidin. Cells were visualized with a light microscope for cell number measurement, or with a confocal microscope. When cells were stimulated with EGF an increase in cell migration and cell association were observed. In FS, S-100 was observed like fibres crossing the cell body and in membrane outgrowth processes. These membrane extensions were directed to other FS. When both cell types were forming clusters, S-100 fibres were observed like involving the cluster. Also, a thin S100 band was seen in the boundary between FS and SC. These data suggest a participation of S-100 in the mechanism of cell interaction between FSs and with SCs in the cluster formation.