Effects of repetitive paired associative stimulation on brain plasticity and working memory in Alzheimer’s disease: a pilot randomized double-blind-controlled trial

2020 ◽  
pp. 1-13
Author(s):  
Sanjeev Kumar ◽  
Reza Zomorrodi ◽  
Zaid Ghazala ◽  
Michelle S. Goodman ◽  
Daniel M. Blumberger ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Working Memory ◽  
Brain Plasticity ◽  
Controlled Trial ◽  
Memory Performance ◽  
Double Blind ◽  
Paired Associative Stimulation ◽  
Post Hoc ◽  
The Impact

ABSTRACT Design: Pilot randomized double-blind-controlled trial of repetitive paired associative stimulation (rPAS), a paradigm that combines transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) with peripheral median nerve stimulation. Objectives: To study the impact of rPAS on DLPFC plasticity and working memory performance in Alzheimer’s disease (AD). Methods: Thirty-two patients with AD (females = 16), mean (SD) age = 76.4 (6.3) years were randomized 1:1 to receive a 2-week (5 days/week) course of active or control rPAS. DLPFC plasticity was assessed using single session PAS combined with electroencephalography (EEG) at baseline and on days 1, 7, and 14 post-rPAS. Working memory and theta–gamma coupling were assessed at the same time points using the N-back task and EEG. Results: There were no significant differences between the active and control rPAS groups on DLPFC plasticity or working memory performance after the rPAS intervention. There were significant main effects of time on DLPFC plasticity, working memory, and theta–gamma coupling, only for the active rPAS group. Further, on post hoc within-group analyses done to generate hypotheses for future research, as compared to baseline, only the rPAS group improved on post-rPAS day 1 on all three indices. Finally, there was a positive correlation between working memory performance and theta–gamma coupling. Conclusions: This study did not show a beneficial effect of rPAS for DLPFC plasticity or working memory in AD. However, post hoc analyses showed promising results favoring rPAS and supporting further research on this topic. (Clinicaltrials.gov-NCT01847586)

scholarly journals A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer’s dementia

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Shifu Xiao ◽  
Piu Chan ◽  
Tao Wang ◽  
Zhen Hong ◽  
Shuzhen Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trial ◽  
Controlled Trial ◽  
Drug Effects ◽  
Disease Assessment ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
The Difference

Abstract Background New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. Methods We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was − 2.15 points (95% confidence interval, − 3.07 to − 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group. Conclusions GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated. Trial registration ClinicalTrials.gov, NCT02293915. Registered on November 19, 2014

scholarly journals Emotional Working Memory and Alzheimer’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Nicola Mammarella ◽  
Beth Fairfield
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Working Memory ◽  
Memory Performance ◽  
Memory Task ◽  
Emotional Information ◽  
Healthy Older Adults ◽  
Affective Stimuli ◽  
Age Related ◽  
Dementia Of Alzheimer’S Type

A number of recent studies have reported that working memory does not seem to show typical age-related deficits in healthy older adults when emotional information is involved. Differently, studies about the short-term ability to encode and actively manipulate emotional information in dementia of Alzheimer’s type are few and have yielded mixed results. Here, we review behavioural and neuroimaging evidence that points to a complex interaction between emotion modulation and working memory in Alzheimer’s. In fact, depending on the function involved, patients may or may not show an emotional benefit in their working memory performance. In addition, this benefit is not always clearly biased (e.g., towards negative or positive information). We interpret this complex pattern of results as a consequence of the interaction between multiple factors including the severity of Alzheimer’s disease, the nature of affective stimuli, and type of working memory task.

scholarly journals A Randomized, Controlled Trial of Linopirdine in the Treatment of Alzheimer's Disease

1997 ◽  
Vol 24 (2) ◽  
pp. 140-145 ◽  
Author(s):  
Kenneth Rockwood ◽  
B. Lynn Beattie ◽  
M. Robin Eastwood ◽  
Howard Feldman ◽  
Erich Mohr ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Controlled Trial ◽  
Small Degree ◽  
Disease Assessment ◽  
Double Blind ◽  
Cognitive Subscale ◽  
Parallel Group ◽  
Treatment Dose ◽  
Age Range

ABSTRACT:Objectives:We tested the efficacy and safety of linopirdine, a novel phenylindolinone, in the treatment of Alzheimer's disease.Methods:A multicentre, randomized, double-blind, parallel group, placebo-controlled trial of linopirdine (30 mg three times per day or placebo). Patients (n = 382, 55% male, 98% Caucasian, age range 51-95 years) with mild or moderate Alzheimer's disease, of whom 375 received at least one treatment dose were analysed. There were no important differences between the groups at baseline.Results:No difference was seen in Clinical Global Impression scores between patients receiving placebo and those receiving linopirdine (n = 189). Small differences in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores were seen throughout the study favouring linopirdine; at 6 months the ADAS-Cog scores were 20.2 (linopirdine) and 22.1 (placebo) p = 0.01.Conclusions:This trial did not detect clinically meaningful differences in patients receiving linopirdine for 6 months, despite evidence of a small degree of improved cognitive function. Further studies may benefit from more sensitive tests of treatment effects in Alzheimer's disease.

Effects of a Non-focal Plasticity Protocol on Apathy in Moderate Alzheimer's Disease: A Randomized, Double-blind, Sham-controlled Trial

2014 ◽  
Vol 7 (2) ◽  
pp. 308-313 ◽  
Author(s):  
Claudia Kimie Suemoto ◽  
Daniel Apolinario ◽  
Ester Miyuki Nakamura-Palacios ◽  
Leonardo Lopes ◽  
Renata Elaine Paraizo Leite ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Controlled Trial ◽  
Double Blind

scholarly journals Adaptive working memory strategy training in early Alzheimer's disease: Randomised controlled trial

2017 ◽  
Vol 210 (1) ◽  
pp. 61-66 ◽  
Author(s):  
J. D. Huntley ◽  
A. Hampshire ◽  
D. Bor ◽  
A. Owen ◽  
R. J. Howard
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Working Memory ◽  
Cognitive Function ◽  
Cognitive Training ◽  
Controlled Trial ◽  
Verbal Working Memory ◽  
Strategy Training ◽  
Post Intervention ◽  
Early Alzheimer’S Disease

BackgroundInterventions that improve cognitive function in Alzheimer's disease are urgently required.AimsTo assess whether a novel cognitive training paradigm based on ‘chunking’ improves working memory and general cognitive function, and is associated with reorganisation of functional activity in prefrontal and parietal cortices (trial registration: ISRCTN43007027).MethodThirty patients with mild Alzheimer's disease were randomly allocated to receive 18 sessions of 30 min of either adaptive chunking training or an active control intervention over approximately 8 weeks. Pre- and post-intervention functional magnetic resonance imaging (fMRI) scans were also conducted.ResultsAdaptive chunking training led to significant improvements in verbal working memory and untrained clinical measures of general cognitive function. Further, fMRI revealed a bilateral reduction in task-related lateral prefrontal and parietal cortex activation in the training group compared with controls.ConclusionsChunking-based cognitive training is a simple and potentially scalable intervention to improve cognitive function in early Alzheimer's disease.

scholarly journals Methylphenidate for Apathy in Community-Dwelling Older Veterans With Mild Alzheimer’s Disease: A Double-Blind, Randomized, Placebo-Controlled Trial

2018 ◽  
Vol 175 (2) ◽  
pp. 159-168 ◽  
Author(s):  
Prasad R. Padala ◽  
Kalpana P. Padala ◽  
Shelly Y. Lensing ◽  
Daniel Ramirez ◽  
Varun Monga ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Controlled Trial ◽  
Community Dwelling ◽  
Double Blind

Is Ongoing Anticholinergic Burden Associated With Greater Cognitive Decline and Dementia Severity in Mild to Moderate Alzheimer’s Disease?

2019 ◽  
Vol 75 (5) ◽  
pp. 987-994 ◽  
Author(s):  
Adam H Dyer ◽  
Claire Murphy ◽  
Ricardo Segurado ◽  
Brian Lawlor ◽  
Sean P Kennelly ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Controlled Trial ◽  
Anticholinergic Medication ◽  
Clinical Dementia Rating ◽  
Dementia Severity ◽  
Increased Risk ◽  
Clinical Covariates ◽  
The Impact ◽  
Anticholinergic Burden

Abstract Background Use of anticholinergic medication is associated with an increased risk of cognitive impairment and/or dementia. Despite this, the impact of continuing medication with anticholinergic properties in those diagnosed with Alzheimer’s Disease (AD) is not clear. Methods Analysis of data from NILVAD, an 18-month randomized controlled trial of Nilvadipine in AD. Effects of ongoing Anticholinergic Cognitive Burden (ACB) on cognition (ADAS-Cog: Alzheimer’s Disease Cog Subsection) and dementia severity (CDR-sb: Clinical Dementia Rating – Sum of Boxes/DAD: Disability Assessment for Dementia) over 18 months was evaluated adjusting for important clinical covariates. Results Just over one-quarter (27.90%, n = 142/510) of patients with mild to moderate AD were prescribed a potential/definite anticholinergic. While ACB score was not associated with greater progression on the ADAS-Cog/CDR-sb over time, a higher total ACB predicted greater dementia severity on the DAD, which persisted after robust covariate adjustment (β Coef: −1.53, 95% CI: −2.83 to −0.23, p = .021). There was a significant interaction between APOE ε4 status and ACB score, with carriers experiencing greater progression on both the CDR-Sb (β Coef: 0.36, 95% CI: 0.05–0.67, p = .021) and DAD (β Coef: −3.84, 95% CI: −7.65 to 0.03, p = .049). Conclusions Ongoing use of anticholinergic medication was associated with greater dementia progression on the DAD, but not the CDR-sb. APOE ε 4 carriers may be particularly vulnerable to the effect of ongoing anticholinergic medication on dementia severity, with significant APOE ε 4 x ACB score interactions demonstrated on both the DAD and CDR-sb.

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