Article

Memantine in moderate to severe Alzheimer’s disease: a meta-analysis of randomised clinical trials

Karolinska Institutet, Stockholm, Sweden.
Dementia and Geriatric Cognitive Disorders (Impact Factor: 2.81). 02/2007; 24(1):20-7. DOI: 10.1159/000102568
Source: PubMed

ABSTRACT The efficacy of memantine in Alzheimer's disease (AD) has been investigated in multiple randomised, placebo-controlled phase III trials. Recently, the indication label for memantine in Europe was extended to cover patients with moderate to severe AD, i.e. Mini-Mental State Exam total scores below 20. The efficacy data for memantine in this patient subgroup has been summarised by a meta-analysis of 1,826 patients in six trials. Efficacy was assessed using measures of global status (Clinician's Interview-Based Impression of Change Plus Caregiver Input), cognition (Alzheimer's Disease Assessment Scale - Cognitive Subscale, or Severe Impairment Battery), function (Alzheimer's Disease Cooperative Study Activities of Daily Living 19- or 23-item scale), and behaviour (Neuropsychiatric Inventory). Results (without replacement of missing values) showed statistically significant effects for memantine (vs. placebo) in each domain. Memantine was well tolerated, and the overall incidence rates of adverse events were comparable to placebo. This meta-analysis supports memantine's clinically relevant efficacy in patients with moderate to severe AD.

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    • "Alzheimer's disease (AD) is the most common form of dementia, affecting more than 27 million people around the world [1] [2]. At present, the available treatment is symptomatic, e.g., cholinesterase inhibitors [3] and memantine [4]. Given the dramatic consequences that the disease imposes on patients, their families, and society, new therapies with disease-modifying effects are urgently needed. "
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    • "An interesting theme that has recently emerged identifies NR2B as a candidate and promising target for modern AD therapeutic strategies (Reisberg et al. 2003; Santangelo et al. 2012). Indeed, several emerging studies have proven the efficacy of antagonists selective for these receptors, which segregate to extrasynaptic compartments, exclusively composed of NR2B subunits, for cognitive-enhancing therapy in AD (Winblad et al. 2007; Porsteinsson et al. 2008). The prevailing view suggests that an increase in glutamate levels for chronic activation of extrasynaptic NMDAR may lead first to death of postsynaptic neurons, followed by synaptotoxicity and ultimately cell death, which correlates with the loss of memory function and learning ability in AD patients (Danysz and Parsons 2012). "
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    • "Transition probabilities were based on the predictive equation established in Rive et al. (2010a). Two major data sources were combined: a metaanalysis of six large multicentre randomized controlled clinical trials for memantine (Winblad et al., 2007), and data from the LASER – AD study. Treatment with memantine prolonged time to full-time care on average by 6 weeks per participant compared to standard care over the 5-year evaluation period, representing a 7% increase in the time to full-time care compared to standard treatment. "
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