Dataset Information

Effect of antiamyloid-β drugs on Alzheimer's disease: study protocol for a systematic review and meta-analysis.

ABSTRACT:

Introduction

Alzheimer's disease (AD) is a neurodegenerative disease with a complex aetiology involving multiple targets and pathways. With the continuous growth of the ageing population, the burden of AD is increasing year by year. However, there has not been new drug approved for over a decade. In addition, the efficacy of memantine and cholinesterase inhibitors is not satisfactory. As amyloid-β (Aβ) is regarded as the core pathological change and the trigger mechanism of AD, anti-Aβ therapy may be an effective therapy. In recent years, a lot of clinical trials have been carried out in this field, but the results have not been well summarised and analysed.

Methods and analysis

In this study, we will study the effect of anti-Aβ antibodies versus placebo on the clinical efficacy, biomarkers, neuroimaging and safety in different stages of AD, as well as the factors that may affect the efficacy. Drugs that only target the existing Aβ are regarded as anti-Aβ antibodies. Following electronic databases will be searched from inception to April 2021: Medline-Ovid, EMBase-Ovid, Cochrane Central and clinical trial registration platform ClinicalTrials.gov. After identifying eligible studies through screening title, abstract and read full text of each retrieved literature, we will contact the correspondence authors for additional information and grey literatures. To get more reliable results, random effect model will be conducted for meta-analysis and analysis of subgroups or subsets. Funnel plot, Egger's test and sensitivity analysis will be conducted to explore potential heterogeneity. Meta-regression will be conducted to identify the factors that may affect clinical efficacy. Evidence quality assessment and trial sequential analysis will be conducted to assess the quality of evidence and confirm the reliability of the results in this study.

Ethics and discussion

This study does not require formal ethical approval. The findings will be submitted to a peer-review journal.

Prospero registration number

CRD42020202370.

SUBMITTER: Lyu D

PROVIDER: S-EPMC8137253 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundThe growing societal and economic impact of Alzheimer's disease (AD) is further compounded by the present lack of disease-modifying interventions. Non-pharmacological intervention approaches, such as exercise, have the potential to be powerful approaches to improve or mitigate the symptoms of AD without added side effects or financial burden associated with drug therapies. Various forms and regiments of exercise (i.e., strength, aerobic, multicomponent) have been reported in the literature; however, conflicting evidence obscures clear interpretation of the value and impact of exercise as an intervention for older adults with AD. The primary objective of this review will be to evaluate the effects of exercise interventions for older adults with AD. In addition, this review will evaluate the evidence quality and synthesize the exercise training prescriptions for proper clinical practice guidelines and recommendations.MethodsThis systematic review and meta-analysis will be carried out by an interdisciplinary collective representing clinical and research stakeholders with diverse expertise related to neurodegenerative diseases and rehabilitation medicine. Literature sources will include the following: Embase, PsychINFO, OVID Medline, and Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily. Inclusion criteria are participants with late onset AD and structured exercise interventions with prescribed duration, frequency, and intensity. The primary outcome of this study will center on improved or sustained cognitive functioning. Secondary outcomes will include institutionalization-related outcomes, ability in activities of daily living, mood and emotional well-being, quality of life, morbidity, and mortality. Analysis procedures to include measurement of bias, data synthesis, sensitivity analysis, and assessment of heterogeneity are described in this protocol.DiscussionThis review is anticipated to yield clinically meaningful insight on the specific value of exercise for older adults with AD. Improved understanding of diverse exercise intervention approaches and their specific impact on various health- and function-related outcomes is expected to guide clinicians to more frequently and accurately prescribe meaningful interventions for those affected by AD.Systematic review registrationPROSPERO CRD42020175016 .

Project description:BackgroundApproximately 35 million people world-wide have Alzheimer's disease and this is projected to nearly double by 2030. Cognitive enhancers, including cholinesterase inhibitors (for example, donepezil, galantamine and rivastigmine) and memantine (N-methyl-D-aspartic acid (NMDA) receptor antagonist) have been approved for the treatment of Alzheimer's disease in many countries. Our objective is to evaluate the comparative effectiveness, safety, and cost of cognitive enhancers for Alzheimer's disease through a systematic review.Methods/designStudies examining the efficacy, safety, and cost of cognitive enhancers compared to placebo, supportive care, and other cognitive enhancers for Alzheimer's patients will be included. The primary outcome is cognition and secondary outcomes include function, behavior, quality of life, safety, and cost. Experimental studies (randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials), quasi-experimental studies (controlled before-after, interrupted time series), and observational studies (cohort, case-control studies) will be eligible for inclusion. Inclusion will not be limited by publication status, time period or language of dissemination.We will search electronic databases (for example, MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Ageline) from inception onwards. The electronic database search will be supplemented by searching for grey literature (for example, conference proceedings, searches in Google and relevant organization websites). Two reviewers will independently screen the studies for inclusion using the eligibility criteria established a priori and independently extract data. Risk of bias will be assessed using the Cochrane Risk of Bias tool for experimental and quasi-experimental studies and the Newcastle Ottawa Scale for observational studies. If deemed appropriate, meta-analysis and network (that is, indirect comparisons) meta-analysis will be conducted.DiscussionOur systematic review will inform the decision of healthcare providers, policy-makers, Alzheimer's patients and family members about the use of cognitive enhancers, by improving their understanding of the costs, benefits and harms that are associated with these agents. PROSPERO REGISTRY NUMBER: CRD42012001948.

Project description:BackgroundWe performed an updated meta-analysis of randomized placebo-controlled trials testing memantine monotherapy for patients with Alzheimer's disease (AD).MethodsThe meta-analysis included randomized controlled trials of memantine monotherapy for AD, omitting those in which patients were also administered a cholinesterase inhibitor. Cognitive function, activities of daily living, behavioral disturbances, global function, stage of dementia, drug discontinuation rate, and individual side effects were compared between memantine monotherapy and placebo groups. The primary outcomes were cognitive function and behavioral disturbances; the others were secondary outcomes.ResultsNine studies including 2433 patients that met the study's inclusion criteria were identified. Memantine monotherapy significantly improved cognitive function [standardized mean difference (SMD)=-0.27, 95% confidence interval (CI)=-0.39 to -0.14, p=0.0001], behavioral disturbances (SMD=-0.12, 95% CI=-0.22 to -0.01, p=0.03), activities of daily living (SMD=-0.09, 95% CI=-0.19 to -0.00, p=0.05), global function assessment (SMD=-0.18, 95% CI=-0.27 to -0.09, p=0.0001), and stage of dementia (SMD=-0.23, 95% CI=-0.33 to -0.12, p=0.0001) scores. Memantine was superior to placebo in terms of discontinuation because of inefficacy [risk ratio (RR)=0.36, 95% CI=0.17¬ to 0.74, p=0.006, number needed to harm (NNH)=non significant]. Moreover, memantine was associated with less agitation compared with placebo (RR=0.68, 95% CI=0.49 to 0.94, p=0.02, NNH=non significant). There were no significant differences in the rate of discontinuation because of all causes, all adverse events, and individual side effects other than agitation between the memantine monotherapy and placebo groups.ConclusionsMemantine monotherapy improved cognition, behavior, activities of daily living, global function, and stage of dementia and was well-tolerated by AD patients. However, the effect size in terms of efficacy outcomes was small and thus there is limited evidence of clinical benefit.