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Intravenous Immunoglobulin for Patients With Alzheimer's Disease: A Systematic Review and Meta-Analysis.

ABSTRACT: AIM:To assess the efficacy and safety of intravenous immunoglobulin (IVIg) for patients with Alzheimer's disease (AD). MATERIALS AND METHODS:We searched electronic databases and other sources for randomized controlled trials comparing IVIg with placebo or other treatment for adults with AD. Primary outcome was change from baseline in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog). RESULTS:Five placebo-controlled trials were included in the meta-analysis. Compared to placebo, IVIg 0.2 and 0.4 g/kg once every two weeks did not change ADAS-Cog score (weighted mean difference: 0.37, 95% confidence interval: -1.46 to 2.20 and 0.77, -1.34 to 2.88, respectively). Furthermore, except for an increase in the incidence of rash, IVIg did not affect the incidence of other adverse events. CONCLUSION:IVIg, albeit safe, is inefficacious for treatment of patients with AD. Future trials targeting earlier stages of disease or applying different dosing regimens may be warranted to clarify its therapeutic potential.

SUBMITTER: Manolopoulos A

PROVIDER: S-EPMC7459191 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Intravenous Immunoglobulin for Patients With Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Manolopoulos Apostolos A Andreadis Panagiotis P Malandris Konstantinos K Avgerinos Ioannis I Karagiannis Thomas T Kapogiannis Dimitrios D Tsolaki Magda M Tsapas Apostolos A Bekiari Eleni E

American journal of Alzheimer's disease and other dementias 20190415 5

<h4>Aim</h4>To assess the efficacy and safety of intravenous immunoglobulin (IVIg) for patients with Alzheimer's disease (AD).<h4>Materials and methods</h4>We searched electronic databases and other sources for randomized controlled trials comparing IVIg with placebo or other treatment for adults with AD. Primary outcome was change from baseline in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog).<h4>Results</h4>Five placebo-controlled trials were included in the meta-analysis. ...[more]

PMID: 30987435

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Project description:ContextGut dysbiosis has been proposed as one of pathologies in patients with Alzheimer's disease (AD) spectrum. Despite such enthusiasm, the relevant results remain substantially controversial.ObjectiveA systematic review and meta-analysis were performed to investigate the differences of gut microbiota (GM) between patients with AD spectrum (including mild cognitive impairment [MCI] and AD) and healthy controls (HC).Data sourcesPubMed, MEDLINE, Scopus, and Cochrane Library from January 2000 to August 2021. Eligibility criteria for study selection: Observational trials and pre-intervention data of intervention trials that investigated the abundance of GM in patients with AD spectrum and HC.Data extraction and synthesisTwo reviewers independently identified articles, extracted data, and evaluated the risk of bias. The effect sizes were performed by a random-effect, inverse-variance weighted model. The effects of different countries and of clinical stages on GM abundance were also examined.Results11 studies consisting of 378 HC and 427 patients with AD spectrum were included in the meta-analysis. Patients with AD, but not MCI, showed significantly reduced GM diversity as compared to HC. We also found more abundance of Proteobacteria, Bifidobacterium and Phascolarctobacterium, but less abundance of Firmicutes, Clostridiaceae, Lachnospiraceae and Rikenellaceae in patients with AD spectrum as compared with HC. The profiles of abundance of Alistipes and Bacteroides in HC and AD spectrum were differentially affected by countries. Finally, when considering clinical stage as a moderator, the comparisons of abundance in Clostridiaceae and Phascolarctobacterium showed large effect sizes, with gradient changes from MCI to AD stage.LimitationsThe inclusion of studies originating only from China and the U.S. was a possible limitation.ConclusionsPatients with AD spectrum demonstrated altered GM abundance, which was differentially mediated by countries and clinical stages.

Project description:Background: Identifying a poor degree of awareness of cognitive decline (ACD) could represent an early indicator of Alzheimer's disease (AD). Objectives: (1) to understand whether there is evidence of poor ACD in the pre-dementia stages of AD; (2) to summarize the main findings obtained investigating ACD in AD; (3) to propose a conceptual framework. Data Sources: We searched Scopus, Pubmed, and the reference lists for studies published up to August 2020. Original research articles must report a measure of ACD and included individuals with AD dementia, or prodromal AD (or MCI), or being at risk for AD. Data Synthesis: All studies covering preclinical, prodromal, and AD dementia were systematically reviewed. We intended to perform a meta-analysis of empirical studies on preclinical AD or prodromal AD (or MCI), to compare ACD between clinical groups. Due to the paucity of literature on preclinical AD, meta-analysis was only possible for prodromal AD (or MCI) studies. Results: We systematically reviewed 283 articles, and conducted a meta-analysis of 18 articles on prodromal AD (or MCI), showing that ACD was not significantly different between patients with amnestic and non-amnestic MCI (SMD = 0.09, p = 0.574); ACD was significantly poorer in amnestic MCI (SMD = -0.56, p = 0.001) and mild AD (SMD = -1.39, p < 0.001) than in controls; ACD was also significantly poorer in mild AD than in amnestic MCI (SMD = -0.75, p < 0.001), as well as poorer than in non-amnestic MCI (SMD = -1.00, p < 0.001). We also discuss key findings on ACD in AD, such as its neural and cognitive correlates. Conclusions and Implications: We propose that patients may be complaining of their initial subtle cognitive changes, but ACD would soon start to decrease. The individual would show mild anosognosia in the MCI stage, and severe anosognosia in dementia. The evaluation of ACD (comparing self-report to cognitive scores or to informant-report) could be useful to guide the clinician toward a timely diagnosis, and in trials targeting early-stage AD.

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.

Dataset Information

Intravenous Immunoglobulin for Patients With Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Publications

Intravenous Immunoglobulin for Patients With Alzheimer's Disease: A Systematic Review and Meta-Analysis.

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