scholarly journals 314 - Effects of Transcranial Direct Current Stimulation (tDCS) on Cognitive Function in Alzheimer’s Dementia

2020 ◽  
Vol 32 (S1) ◽  
pp. 72-72
Author(s):  
Carol Sheei-Meei Wang ◽  
Kuo-Sheng Cheng ◽  
Chia-Hung Tang ◽  
Nien-Tsen Hou ◽  
Pei-Fang Chien ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Controlled Trial ◽  
Long Term Potentiation ◽  
Alzheimer’S Dementia ◽  
Active Group ◽  
Double Blind ◽  
Alzheimer's Dementia ◽  
Before And After ◽  
Conceptual Ability

Introduction:Identifying effective treatments is a critical issue for Alzheimer’s dementia (AD). The pathological amyloid deposits of AD result in disruption of the balance between long-term potentiation (LTP) and long-term depression (LTD) of neuronal cells and synaptic plasticity. Brain stimulation in dementia research, especially with relatively safe tDCS, has been taken seriously recently. In theory, tDCS affects long-term synaptic plasticity through LTP and LTD, thereby improving cognitive ability. Recently, an increasing number of studies have been conducted to evaluate the efficacy of tDCS in AD and concluded a positive therapeutic effect. Currently, there are no studies of tDCS for AD in Taiwan. In this study, we investigate the effects of tDCS in AD.Method:Using a double-blind, randomized and sham- controlled trial design, Sixteen AD aged 55-90 years (8 active, mean age 73.88 and 8 sham, mean age 74.75) were included in the study. AD diagnostics is according to DSM-5 criteria. The CDR ratings of AD participants ranged from 0.5 to 2. All subjects completed ten consecutive daily sessions in which they received either an active or a sham tDCS over the left dorsal lateral prefrontal cortex (anodal) and a cathodal electrode on the right supraorbital area. In each session, we applied a current intensity of 2 mA and an electrode size of 35 cm2 for 30 min in the active group. All subjects received a series of neuropsychological tests, which included CDR, MMSE, CASI and WCST, before and after these treatment sessions on the first day and 4 weeks later. Chi- square test, Wilcoxon signed ranks test and Mann-Whitney U test were used to assess the differences in participant demographic characteristics and to compare the differences among groups.Results:The active group showed significant improvement in total correct item, Conceptual level Responses (reflecting insight into the correct sorting principles), Categories Completed (reflecting overall success), and Trials to complete first categories (reflecting initial conceptual ability) of WCST 4 weeks later after the final stimulation. There were no statistically significant differences between before and after the 10-session course for the sham group.Conclusion:tDCS stimulation improves cognitive operation and Conceptual Ability of AD.

Priming-Induced Shift in Synaptic Plasticity in the Rat Hippocampus

1999 ◽  
Vol 82 (4) ◽  
pp. 2024-2028 ◽  
Author(s):  
Hongyan Wang ◽  
John J. Wagner
Keyword(s):  
Synaptic Plasticity ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Crossover Point ◽  
Term Potentiation ◽  
Before And After ◽  
History Of ◽  
The Brain ◽  
Dependent Mechanism

The activity history of a given neuron has been suggested to influence its future responses to synaptic input in one prominent model of experience-dependent synaptic plasticity proposed by Bienenstock, Cooper, and Munro (BCM theory). Because plasticity of synaptic plasticity (i.e., metaplasticity) is similar in concept to aspects of the BCM proposal, we have tested the possibility that a form of metaplasticity induced by a priming stimulation protocol might exhibit BCM-like characteristics. CA1 field excitatory postsynaptic potentials (EPSPs) obtained from rat hippocampal slices were used to monitor synaptic responses before and after conditioning stimuli (3–100 Hz) of the Schaffer collateral inputs. A substantial rightward shift (>5-fold) in the frequency threshold between long-term depression (LTD) and long-term potentiation (LTP) was observed <1 h after priming. This change in the LTD/P crossover point occurred at both primed and unprimed synaptic pathways. These results provide new support for the existence of a rapid, heterosynaptic, experience-dependent mechanism that is capable of modifying the synaptic plasticity phenomena that are commonly proposed to be important for developmental and learning/memory processes in the brain.

scholarly journals Efficacy of Memantine for Agitation in Alzheimer’s Dementia: A Randomised Double-Blind Placebo Controlled Trial

PLoS ONE ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. e35185 ◽  
Author(s):  
Chris Fox ◽  
Monica Crugel ◽  
Ian Maidment ◽  
Bjorn Henrik Auestad ◽  
Simon Coulton ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Alzheimer’S Dementia ◽  
Double Blind ◽  
Alzheimer's Dementia ◽  
Double Blind Placebo

scholarly journals 418 - Long-term Effect of Transcranial Direct Current Stimulation (tDCS) in Alzheimer’s

2021 ◽  
Vol 33 (S1) ◽  
pp. 40-41
Author(s):  
Carol Sheei-Meei Wang ◽  
Kuo-Sheng Cheng ◽  
Chia-Hung Tang ◽  
Nien-Tsen Hou ◽  
Pei-Fang Chien ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Direct Current ◽  
Transcranial Direct Current Stimulation ◽  
Long Term Potentiation ◽  
Chi Square ◽  
Double Blind ◽  
Direct Current Stimulation ◽  
Beneficial Effects ◽  
The Right

AbstractIntroduction:To explore and develop effective treatments is crucial for patients with Alzheimer’s dementia (AD). In pathology, the amyloid deposits of AD result in disruption of the balance between long-term potentiation (LTP) and long-term depression (LTD) of neuronal cells and synaptic plasticity. Transcranial direct current stimulation (tDCS) has been proposed to affect long-term synaptic plasticity through LTP and LTD, thereby improving cognitive ability. Although an increasing number of studies have been concluded a positive therapeutic effect on cognition in AD, tDCS studies to date are limited on exploring the duration of its efficacy. In this pilot study, we investigate the effects of tDCS in AD and verify its extending beneficial effects for 3 months follow-up period after the end of stimulation.Method:34 AD participants aged 55-90 years (mean age 75.9 (66-86)) were included in a double-blind, randomized, sham-controlled crossover study. All participants were randomly assigned to receive 10 consecutive daily sessions of active tDCS (or sham) and switched groups 3 months later. The anodal electrode was on the left dorsal lateral prefrontal cortex and the cathodal electrode was on the right supraorbital area. In each active session, we applied a current intensity of 2 mA and an electrode size of 25 cm2 for 30 min in the active group. All subjects received a series of neuropsychological assessments including CDR, MMSE, CASI and WCST at baseline and in 2 weeks, 4 weeks, and 12 weeks post-tDCS (or sham) 10 sessions. Chi-square tests, Wilcoxon signed rank tests and Mann-Whitney U tests were used to assess the differences in participant demographic characteristics and to compare the differences of test scores between groups.Results:The active tDCS group showed significant improvements on CASI total scores from baseline to 2-weeks, 1-month and 3-months after active stimulations, though the improvement declined over time. There are also different presentations in total correct items, conceptual level responses, failure to maintain sets of WCST between active tDCS and sham groups. There is no difference in MMSE, CASI and WCST scores in the sham groups.Conclusion:These results suggest a long term-beneficial effects of tDCS in AD.

Bidirectional Synaptic Plasticity Correlated With the Magnitude of Dendritic Calcium Transients Above a Threshold

2001 ◽  
Vol 85 (1) ◽  
pp. 399-406 ◽  
Author(s):  
R. J. Cormier ◽  
A. C. Greenwood ◽  
J. A. Connor
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Ca1 Neurons ◽  
Test Stimulation ◽  
Term Potentiation ◽  
Hippocampal Ca1 ◽  
Before And After ◽  
Activity Dependent ◽  
Stimulation Of

The magnitude of postsynaptic Ca2+ transients is thought to affect activity-dependent synaptic plasticity associated with learning and memory. Large Ca2+ transients have been implicated in the induction of long-term potentiation (LTP), while smaller Ca2+ transients have been associated with long-term depression (LTD). However, a direct relationship has not been demonstrated between Ca2+ measurements and direction of synaptic plasticity in the same cells, using one induction protocol. Here, we used glutamate iontophoresis to induce Ca2+ transients in hippocampal CA1 neurons injected with the Ca2+-indicator fura-2. Test stimulation of one or two synaptic pathways before and after iontophoresis showed that the direction of synaptic plasticity correlated with glutamate-induced Ca2+ levels above a threshold, below which no plasticity occurred (∼180 nM). Relatively low Ca2+ levels (180–500 nM) typically led to LTD of synaptic transmission and higher levels (>500 nM) often led to LTP. Failure to show plasticity correlated with Ca2+ levels in two distinct ranges: <180 nM and ∼450–600 nM, while only LTD occurred between these ranges. Our data support a class of models in which failure of Ca2+ transients to affect transmission may arise either from insufficient Ca2+ to affect Ca2+-sensitive proteins regulating synaptic strength through opposing activities or from higher Ca2+ levels that reset activities of such proteins without affecting the net balance of activities. Our estimates of the threshold Ca2+ level for LTD (∼180 nM) and for the transition from LTD to LTP (∼540 nM) may assist in constraining the molecular details of such models.

scholarly journals EGb 761® Does Not Affect Blood Coagulation and Bleeding Time in Patients with Probable Alzheimer’s Dementia—Secondary Analysis of a Randomized, Double-Blind Placebo-Controlled Trial

Healthcare ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1678
Author(s):  
Charlotte Kloft ◽  
Robert Hoerr
Keyword(s):  
Acetylsalicylic Acid ◽  
Prothrombin Time ◽  
Bleeding Time ◽  
Controlled Trial ◽  
International Normalized Ratio ◽  
Alzheimer’S Dementia ◽  
Egb 761 ◽  
Double Blind ◽  
Alzheimer's Dementia ◽  
Double Blind Placebo

Following reports of bleeding upon Ginkgo intake, we assessed whether Ginkgo extract EGb 761® affects coagulation or platelet function or increases the risk of bleeding. In a double-blind, placebo-controlled trial, prothrombin time, activated partial thromboplastin time, international normalized ratio and bleeding time were measured in patients with Alzheimer’s dementia at baseline, weeks 6 and 26. A total of 513 patients were randomized to 120 mg (n = 169) or 240 mg EGb 761® (n = 170) or placebo (n = 174). No relevant changes were found for coagulation parameters and bleeding time. Numbers of bleeding-related adverse events were similar in all groups. Concomitant intake of acetylsalicylic acid was documented for 68 patients in the placebo group and 105 in the EGb 761® groups. Within these groups, the means at baseline and week 26 differed by less than 1 unit for prothrombin time and bleeding time and less than 0.1 unit for international normalized ratio. Data on warfarin treatment in nine patients each taking placebo or EGb 761® did not indicate enhancement of warfarin effects by EGb 761®. No evidence was found that EGb 761® affects hemostasis or increases the bleeding risk. No pharmacodynamic interactions with warfarin or acetylsalicylic acid were found.

Long-term cariprazine treatment for the prevention of relapse in patients with schizophrenia: A randomized, double-blind, placebo-controlled trial

2020 ◽  
pp. 27-37
Author(s):  
Suresh Durgam ◽  
Willie Earley ◽  
Rui Li ◽  
Dayong Li ◽  
Kaifeng Lu ◽  
...  
Keyword(s):  
Safety Profile ◽  
Relapse Prevention ◽  
Controlled Trial ◽  
Fixed Dose ◽  
Open Label ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Randomized Controlled ◽  
Time To Relapse

Cariprazine, a dopamine D3/D2 receptor partial agonist with preference for D3 receptors, has demonstrated efficacy in randomized controlled trials in schizophrenia. This multinational, randomized, double-blind, placebo-controlled, parallel-group study evaluated the efficacy, safety, and tolerability of cariprazine for relapse prevention in adults with schizophrenia; total study duration was up to 97 weeks. Schizophrenia symptoms were treated/stabilized with cariprazine 3—9 mg/d during 20-week open-label treatment consisting of an 8-week, flexible-dose run-in phase and a 12-week fixed-dose stabilization phase. Stable patients who completed open-label treatment could be randomized to continued cariprazine (3, 6, or 9 mg/d) or placebo for double-blind treatment (up to 72 weeks). The primary efficacy parameter was time to relapse (worsening of symptom scores, psychiatric hospitalization, aggressive/violent behavior, or suicidal risk); clinical measures were implemented to ensure safety in case of impending relapse. A total of 264/765 patients completed open-label treatment; 200 eligible patients were randomized to double-blind placebo (n = 99) or cariprazine (n = 101). Time to relapse was significantly longer in cariprazine — versus placebo-treated patients (P = .0010, log-rank test). Relapse occurred in 24.8% of cariprazine- and 47.5% of placebo-treated patients (hazard ratio [95% CI] = 0.45 [0.28, 0.73]). Akathisia (19.2%), insomnia (14.4%), and headache (12.0%) were reported in ≥ 10% of patients during open-label treatment; there were no cariprazine adverse events ≥ 10% during double-blind treatment. Long-term cariprazine treatment was significantly more effective than placebo for relapse prevention in patients with schizophrenia. The long-term safety profile in this study was consistent with the safety profile observed in previous cariprazine clinical trials. ClincalTrials.gov identifier: NCT01412060. Key words: schizophrenia; cariprazine; long-term treatment; relapse prevention; randomized controlled trial; oral antipsychotics

Brivaracetam Prevents the Over-expression of Synaptic Vesicle Protein 2A and Rescues the Deficits of Hippocampal Long-term Potentiation In Vivo in Chronic Temporal Lobe Epilepsy Rats

2020 ◽  
Vol 17 (4) ◽  
pp. 354-360 ◽  
Author(s):  
Yu-Xing Ge ◽  
Ying-Ying Lin ◽  
Qian-Qian Bi ◽  
Yu-Juan Chen
Keyword(s):  
Synaptic Plasticity ◽  
Temporal Lobe Epilepsy ◽  
Synaptic Vesicle ◽  
Long Term Potentiation ◽  
Synaptic Dysfunction ◽  
Over Expression ◽  
Term Potentiation ◽  
Synaptic Vesicle Protein 2A

Background: Patients with temporal lobe epilepsy (TLE) usually suffer from cognitive deficits and recurrent seizures. Brivaracetam (BRV) is a novel anti-epileptic drug (AEDs) recently used for the treatment of partial seizures with or without secondary generalization. Different from other AEDs, BRV has some favorable properties on synaptic plasticity. However, the underlying mechanisms remain elusive. Objective: The aim of this study was to explore the neuroprotective mechanism of BRV on synaptic plasticity in experimental TLE rats. Methods: The effect of chronic treatment with BRV (10 mg/kg) was assessed on Pilocarpine induced TLE model through measurement of the field excitatory postsynaptic potentials (fEPSPs) in vivo. Differentially expressed synaptic vesicle protein 2A (SV2A) were identified with immunoblot. Then, fast phosphorylation of synaptosomal-associated protein 25 (SNAP-25) during long-term potentiation (LTP) induction was performed to investigate the potential roles of BRV on synaptic plasticity in the TLE model. Results: An increased level of SV2A accompanied by a depressed LTP in the hippocampus was shown in epileptic rats. Furthermore, BRV treatment continued for more than 30 days improved the over-expression of SV2A and reversed the synaptic dysfunction in epileptic rats. Additionally, BRV treatment alleviates the abnormal SNAP-25 phosphorylation at Ser187 during LTP induction in epileptic ones, which is relevant to the modulation of synaptic vesicles exocytosis and voltagegated calcium channels. Conclusion: BRV treatment ameliorated the over-expression of SV2A in the hippocampus and rescued the synaptic dysfunction in epileptic rats. These results identify the neuroprotective effect of BRV on TLE model.

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