scholarly journals Efficacy of Memantine, Donepezil, or Their Association in Moderate-Severe Alzheimer’s Disease: A Review of Clinical Trials

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Ivana Molino ◽  
Luisa Colucci ◽  
Angiola M. Fasanaro ◽  
Enea Traini ◽  
Francesco Amenta
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Symptomatic Treatment ◽  
Assessment Tools ◽  
Double Blind ◽  
The Usa ◽  
High Doses ◽  
Short Time ◽  
Che Inhibitors

Background. Acetylcholinesterase (AChE)/cholinesterase (ChE) inhibitors (Is) and memantine are licensed for symptomatic treatment of mild-moderate and moderate-severe forms of Alzheimer’s disease (AD), respectively. High doses of the AChE-I donepezil were licensed in the USA for moderate-severe AD, and the association AChE/ChE-Is plus memantine was proposed for AD at this stage.Objectives. This paper has reviewed evidence from clinical trials of the effectiveness of memantine, donepezil, or the two drugs in association in managing moderate-severe AD.Method. Double-blind, placebo-controlled randomized trials (RCTs) using memantine or donepezil alone or in association versus placebo in moderate-severe AD were reviewed. Analysis done in January 2013 considered the years 2007–2012.Results and Conclusion. Only 83 of the 941 papers selected were considered relevant, and only 13 met the criterion of “adequacy and representativeness.” Memantine and donepezil lead to improvements in moderate-to-severe AD and the choice between the compounds should be based on their contraindications more than on disease severity. No evidence was found of advantages of the association of memantine-donepezil. The heterogeneity of conditions explored by RCTs, the relatively short time of observation (24–52 weeks), and the different cognitive assessment tools used did not allow comparing properly different trials.

Rosiglitazone and Pioglitazone for the Treatment of Alzheimer's Disease

2011 ◽  
Vol 45 (11) ◽  
pp. 1416-1424 ◽  
Author(s):  
Benjamin W Miller ◽  
Kristine C Willett ◽  
Alicia R Desilets
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Safety Data ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Search Terms ◽  
Primary Endpoints ◽  
Study Selection ◽  
Antiinflammatory Effects

Objective: To review the literature on the efficacy and safety of rosiglitazone and pioglitazone for the treatment of Alzheimer's disease (AD). Data Sources: Literature was accessed through MEDLINE (1948-August 2011 week 2) and EMBASE (1980-2011 week 32) using the search terms rosiglitazone, pioglitazone, and Alzheimer's disease. Results were limited to studies conducted in humans and published in English. Study Selection And Data Ektraction: Clinical trials evaluating the efficacy and safety of rosiglitazone or pioglitazone in patients with AD were critically evaluated. Data Synthesis: The mechanism for development of AD has been linked to both inflammation and decreased insulin sensitivity. Because of this, rosiglitazone and pioglitazone have been evaluated as potential treatments for AD because of their insulin-sensitizing and antiinflammatory effects. Five clinical trials were evaluated (3 assessing rosiglitazone, 2 assessing pioglitazone); 1 trial evaluating rosiglitazone demonstrated a beneficial effect on cognition in patients with probable AD. However, the largest randomized, double-blind, placebo-controlled trials conducted to date failed to demonstrate a difference between rosiglitazone and placebo when assessing primary endpoints. Two small trials evaluating pioglitazone produced conflicting results regarding efficacy in AD; numerous limitations make results difficult to interpret. The safety of these agents was also evaluated in these trials; edema was seen more commonly in patients receiving rosiglitazone or pioglitazone than in those receiving placebo; however, each drug was generally well tolerated. Conclusions: Resufts from clinical trials and current safety data suggest that rosiglitazone should not be used for the treatment of AD. Application of results from trials evaluating pioglitazone in the treatment of AD is limited because of major trial limitations; therefore, it should not be recommended at this time. Although these drugs are not commonly used in the treatment of AD, further pharmacoepidemiologic studies are warranted before their use can be recommended.

scholarly journals Broader Considerations of Higher Doses of Donepezil in the Treatment of Mild, Moderate, and Severe Alzheimer's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Camryn Berk ◽  
Marwan Sabbagh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Nicotinic Receptor ◽  
Acetylcholinesterase Inhibitor ◽  
Symptomatic Treatment ◽  
Mechanisms Of Action ◽  
Receptor Stimulation ◽  
App Processing ◽  
Higher Doses

Donepezil, a highly selective acetylcholinesterase inhibitor (AChEI), is approved as a symptomatic treatment mild, moderate, and severe Alzheimer's disease (AD). Donepezil exerts its treatment effect through multiple mechanisms of action including nicotinic receptor stimulation, mitigation of excitotoxicity, and influencing APP processing. The use of donepezil at higher doses is justified given the worsening cholinergic deficit as the disease advances. Donepezil has been investigated in several clinical trials of subjects with moderate-to-severe AD. While the side effects are class specific (cholinergically driven), demonstrable benefit has been shown at the 10 mg dose and the 23 mg doses. Here, we review the clinical justification, efficacy, safety, and tolerability of use of donepezil in the treatment of moderate-to-severe AD.

scholarly journals Monoclonal antibodies: a new trend for the treatment of Alzheimer’s disease?

2021 ◽  
Author(s):  
Letícia Escorse Requião ◽  
Giulia Freitas ◽  
Mayanna Macedo ◽  
Hanny Gondim ◽  
Blenda Antunes ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Amyloid Peptide ◽  
Phase Iii ◽  
Functional Improvement ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Pubmed Database

Introduction: Alzheimer’s disease (AD) is the main form of senile dementia. Most of the supposedly disease-modifying treatments in development are directed against the β-amyloid peptide, the administration of exogenous anti-Aβ monoclonal antibodies is a passive immunization strategy aimed at resolving the aggregation of this substance. Objective: Analyze the effectiveness of monoclonal antibodies in the treatment of Alzheimer’s disease. Methods: This is a literature review, based on randomized clinical trials published between 2014 and 2021. The search was conducted in the PubMed database. Results: According to the eligibility criteria, 10 articles were selected. Two of the randomized, double-blind, placebo-controlled phase III studies, one published in 2018 and the other published in 2016, evaluated the intervention with Solanezumab and Bapineuzumab, respectively. Both were not shown to be statistically significant (P = 0.10) for the outcome improvement of the score in the cognitive subscale of 14 and 11 items “Alzheimer’s Disease Assessment Scale” (ADAS-cog14 / 11). However, in a phase II randomized placebo-controlled clinical trial, published in 2021, the use of Donanemab in patients with early Alzheimer’s disease resulted in statistically significant cognitive and functional improvement (P = 0.04) for the outcome change in the scale “Integrated Alzheimer’s Disease Rating” (iADR). Conclusion: Although the use of Donanemab has resulted in cognitive and functional improvement, randomized, double-blind, placebo-controlled, phase III clinical trials need to be conducted to prove the efficacy and safety of its use in clinical practice. Other monoclonal antibodies evaluated did not demonstrate evidence of benefit.

scholarly journals Effect of Age on Clinical Trial Outcome in Participants with Probable Alzheimer’s Disease

2021 ◽  
pp. 1-15
Author(s):  
Steven D. Targum ◽  
Lisa Fosdick ◽  
Kristen E. Drake ◽  
Paul B. Rosenberg ◽  
Anna D. Burke ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Rating Scale ◽  
Disease Assessment ◽  
Age Group ◽  
Double Blind ◽  
Subject Selection ◽  
Time Interaction ◽  
Intent To Treat

Background: Age may affect treatment outcome in trials of mild probable Alzheimer’s disease (AD). Objective: We examined age as a moderator of outcome in an exploratory study of deep brain stimulation targeting the fornix (DBS-f) region in participants with AD. Methods: Forty-two participants were implanted with DBS electrodes and randomized to double-blind DBS-f stimulation (“on”) or sham DBS-f (“off”) for 12 months. Results: The intervention was safe and well tolerated. However, the selected clinical measures did not differentiate between the “on” and “off” groups in the intent to treat (ITT) population. There was a significant age by time interaction with the Alzheimer’s Disease Assessment Scale; ADAS-cog-13 (p = 0.028). Six of the 12 enrolled participants <  65 years old (50%) markedly declined on the ADAS-cog-13 versus only 6.7%of the 30 participants≥65 years old regardless of treatment assignment (p = 0.005). While not significant, post-hoc analyses favored DBS-f “off” versus “on” over 12 months in the <  65 age group but favored DBS-f “on” versus “off” in the≥65 age group on all clinical metrics. On the integrated Alzheimer’s Disease rating scale (iADRS), the effect size contrasting DBS-f “on” versus “off” changed from +0.2 (favoring “off”) in the <  65 group to –0.52 (favoring “on”) in the≥65 age group. Conclusion: The findings highlight issues with subject selection in clinical trials for AD. Faster disease progression in younger AD participants with different AD sub-types may influence the results. Biomarker confirmation and genotyping to differentiate AD subtypes is important for future clinical trials.

scholarly journals Cerebrolysin in Mild-to-Moderate Alzheimer's Disease: A Meta-Analysis of Randomized Controlled Clinical Trials

2015 ◽  
Vol 39 (5-6) ◽  
pp. 332-347 ◽  
Author(s):  
Serge Gauthier ◽  
Jefferson Voltaire Proaño ◽  
Jianping Jia ◽  
Lutz Froelich ◽  
Johannes Christophe Vester ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cognitive Function ◽  
Meta Analysis ◽  
Controlled Clinical Trials ◽  
Clinical Change ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Randomized Controlled

Objective: The aim of this study was to provide a systematic and quantitative summary of benefit and risk of Cerebrolysin in patients with mild-to-moderate Alzheimer's disease (AD) and to avoid major deficiencies of an earlier meta-analysis. Design: This is a meta-analysis of randomized double-blind placebo-controlled clinical trials. Data Sources: Trials were identified with the help of PubMed, the Cochrane Dementia Group database, the Center for Collaborative Neurosciences, and references from reviews; no language restrictions were applied. Study Selection: All randomized double-blind placebo-controlled studies on 30 ml/day of Cerebrolysin in mild-to-moderate AD were included. Results: There were 6 eligible randomized controlled trials comparing Cerebrolysin with placebo. For all studies, either individual patient data and/or published data (aggregate data) were available. Analyses were based on the odds ratio (OR) for dichotomized global clinical change and for safety criteria, on the standardized mean difference (SMD) for pooling of cognitive function, and on the Mann-Whitney statistic (MW) for multivariate analysis of ‘global benefit' (combined effect of global clinical change and cognitive function). Cerebrolysin was significantly more effective than placebo at 4 weeks regarding cognitive function (4 weeks: SMD -0.40 points; 95% CI -0.66 to -0.13; p = 0.0031; 6 months: SMD -0.37 points; 95% CI -0.90 to 0.16; p = 0.1710), at 4 weeks and 6 months regarding global clinical change (4 weeks: OR 3.32; 95% CI 1.20-9.21; p = 0.0212; 6 months: OR 4.98; 95% CI 1.37-18.13; p = 0.0150), and at 4 weeks and 6 months regarding ‘global benefit' (combined efficacy criteria; 4 weeks: MW 0.57, 95% CI 0.53-0.61; p = 0.0006; 6 months: MW 0.57; 95% CI 0.53-0.61; p = 0.0010). The safety aspects of Cerebrolysin were comparable to placebo. Conclusion: This meta-analysis provides evidence that Cerebrolysin has an overall beneficial effect and a favorable benefit-risk ratio in patients with mild-to-moderate AD. Cerebrolysin as a therapeutic agent should be considered by clinicians seeking treatment options for mild-to-moderate AD.

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