Meta‐analysis of six‐month memantine trials in Alzheimer's disease

Doody, Rachelle S.; Tariot, Pierre N.; Pfeiffer, Eric; Olin, Jason T.; Graham, Stephen M.

doi:10.1016/j.jalz.2006.10.004

Cited by 82 publications

(49 citation statements)

References 24 publications

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“…Patients in the studies were randomly assigned to either placebo or active treatment, and treatment arms were equally balanced with regard to age, gender, etc. The standardized effect size of Cerebrolysin on the cognitive domain in the present analysis (SMD -0.37, OC, month 6) was comparable to the range seen for other antidementia treatments [18,20,39,40,41,42]. The effect size of Cerebrolysin on the global domain (OR 4.98), as assessed by the CIBIC+ instrument (by itself a measure of clinical relevance) or CGI, supported the clinical importance of this cognitive benefit.…”

Section: Discussionsupporting

confidence: 82%

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

Gauthier

Proaño

Jia

et al. 2015

Dement Geriatr Cogn Disord

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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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Section: Discussionsupporting

confidence: 82%

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

Gauthier

Proaño

Jia

et al. 2015

Dement Geriatr Cogn Disord

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“…Previous studies, for example, are focused on the use of NMDAR antagonists, like memantine or (+) MK-801 as AD treatments [29,30]. In fact, memantine is one of the few FDA approved drugs for AD [43,44].…”

Section: Discussionmentioning

confidence: 99%

The Level of NMDA Receptor in the Membrane Modulates Amyloid-β Association and Perforation

Peters

Sepúlveda

Fernández-Pérez

et al. 2016

JAD

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Abstract. Alzheimer's disease is a neurodegenerative disorder that affects mostly the elderly. The main histopathological markers are the senile plaques formed by amyloid-␤ peptide (A␤) aggregates that can perforate the plasma membrane of cells, increasing the intracellular calcium levels and releasing synaptic vesicles that finally lead to a delayed synaptic failure. Several membrane proteins and lipids interact with A␤ affecting its toxicity in neurons. Here, we focus on NMDA receptors (NMDARs) as proteins that could be modulating the association and neurotoxic perforation induced by A␤ on the plasma membrane. In fact, our results showed that decreasing NMDARs, using enzymatic or siRNA approaches, increased the association of A␤ to the neurons. Furthermore, overexpression of NMDARs also resulted in an enhanced association between NMDA and A␤. Functionally, the reduction in membrane NMDARs augmented the process of membrane perforation. On the other hand, overexpressing NMDARs had a protective effect because A␤ was now unable to cause membrane perforation, suggesting a complex relationship between A␤ and NMDARs. Because previous studies have recognized that A␤ oligomers are able to increase membrane permeability and produce amyloid pores, the present study supports the conclusion that NMDARs play a critical protective role on A␤ actions in hippocampal neurons. These results could explain the lack of correlation between brain A␤ burden and clinically observed dementia.

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“…двойных слепых плацебо-контроли-руемых исследований [22][23][24][25][26][27] мемантин был заре-гистрирован Европейским медицинским агент-ством (ЕМА), а позднее -и FDA США для лечения только пациентов с умеренной и тяжелой БА, т.е. для тех, когнитивные функции которых по шкале MMSE составляют менее 20 баллов [22].…”

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“…В метаанали-зе R. Doody и соавт. [25] проанализированы данные по общей популяции больных БА, включавшей в том числе пациентов с мягкой деменцией. В метаанализ IQWiG [26] вошли данные тех же основных клинических исследований, которые бы-ли дополнены результатами клинического испыта-ния LU 10116 [27].…”

unclassified

“…Например, в метаанализе R. Doody [25], поведенче-ские эффекты оказались недостоверными. По заре-гистрированному показанию достоверный эффект был установлен в метаанализе B. Winblad [24], а так-же при применении комбинированной терапии с ингибиторами АХЭ в клиническом исследовании MEM-MD-02.…”

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Memantine in treatment of Alzheimer’s disease: 20 years of clinical use

Гаврилова

2016

Z. nevrol. psikhiatr. im. S.S. Korsakova

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Болезнь Альцгеймера (БА) -прогрессирующее нейродегенеративное заболевание, которое харак-теризуется постепенной утратой памяти, других когнитивных функций и способности выполнять повседневные виды деятельности вплоть до полного их распада. На разных этапах БА могут возникать различные психопатологические и поведенческие расстройства, включая физическую агрессию, бес-покойство, неадекватное социальное поведение, ажитацию, депрессию, бред.БА связана с большими экономическими поте-рями. В 2010 г. общая стоимость расходов на боль-ных деменцией (бо`льшая часть из которой обуслов-лена БА) в Европе оценивалась в 105,2 млн евро, составляя 13% от всех расходов на больных с заболе-ваниями головного мозга [1]. К 2050 г. ожидается многократный рост бремени БА в связи с дальней-шим мировым ростом численности таких больных.К сожалению, в настоящее время отсутствуют радикальные средства лечения и профилактики это-го заболевания. Наиболее реалистической целью те-рапии БА является предотвращение прогрессирова-ния деменции и предупреждение появления связан-ных с ней поведенческих и психотических симпто- Recommendations for clinicians on the use of memantine in patients with aD are presented.

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Meta‐analysis of six‐month memantine trials in Alzheimer's disease

Abstract: Memantine consistently benefited patients in all stages of AD and was well-tolerated.

Cited by 82 publications

References 24 publications

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

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

The Level of NMDA Receptor in the Membrane Modulates Amyloid-β Association and Perforation

Memantine in treatment of Alzheimer’s disease: 20 years of clinical use

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