Memantine for dementia.
ABSTRACT Alzheimer's disease, vascular and mixed dementia are the three commonest forms of dementia affecting older people. There is evidence that the excitatory activity of L-glutamate plays a role in the pathogenesis of Alzheimer's disease and in the damage from an ischaemic stroke. A low affinity antagonist to N-Methyl-D-aspartate (NMDA) type receptors, such as memantine, may prevent excitatory amino acid neurotoxicity without interfering with the physiological actions of glutamate required for memory and learning.
To determine the clinical efficacy and safety of memantine for people with Alzheimer's disease, or vascular or mixed dementia.
Trials were identified from a search of the Trial-based Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 7 April 2004 using the terms: memantin*, namenda*, ebixa*, axura*, D-145, DMAA, DRG-0267. All major health care databases and many ongoing trial databases are searched regularly to keep this Register up to date.
Double-blind, parallel group, placebo-controlled, randomised and unconfounded trials in which memantine was administered to people with dementia.
Data were extracted, pooled where possible, and weighted mean differences, standardized mean differences or odds ratios were estimated. Intention-to-treat (ITT) and observed cases (OC) analyses are reported, where data were available.
The evidence suggests that memantine has a positive effect on cognition, mood and behaviour and the ability to perform activities of daily living in patients with moderate to severe Alzheimer's disease. The results in patients with mild to moderate vascular dementia, suggest a beneficial effect of 20mg/day of memantine on cognitive function measured at 28 weeks. However, these results are neither supported by an effect on ability to perform activities of daily living nor by an effect on the clinical impression of change. This suggests that, in patients with mild to moderate vascular dementia, the effect on cognitive function is not translated into clinically detectable changes.
:Memantine 20 mg/day caused a clinically noticeable reduction in deterioration over 28 weeks in patients with moderate to severe Alzheimer disease. This was supported by less functional and cognitive deterioration. Patients taking memantine were less likely to become agitated. The effect in mild to moderate AD is unknown. Patients with mild to moderate vascular dementia receiving memantine 20 mg/day had less cognitive deterioration at 28 weeks but the effects were not clinically discernible. There is an early beneficial effect on cognition, mood, behaviour and clinical impression for memantine at 6 weeks. The drug is well tolerated in general and the incidence of adverse effects is low.
SourceAvailable from: Laurent Lecanu[Show abstract] [Hide abstract]
ABSTRACT: Alzheimer's disease (AD), for which there is no cure, is the most common form of dementia in the elderly. Despite tremendous efforts by the scientific community, the AD drug development pipeline remains extremely limited. Animal models of disease are a cornerstone of any drug development program and should be as relevant as possible to the disease, recapitulating the disease phenotype with high fidelity, to meaningfully contribute to the development of a successful therapeutic agent. Over the past two decades, transgenic models of AD based on the known genetic origins of familial AD have significantly contributed to our understanding of the molecular mechanisms involved in the onset and progression of the disease. These models were extensively used in AD drug development. The numerous reported failures of new treatments for AD in clinical trials indicate that the use of genetic models of AD may not represent the complete picture of AD in humans and that other types of animal models relevant to the sporadic form of the disease, which represents 95% of AD cases, should be developed. In this review, we will discuss the evolution of non-transgenic rat models of AD and how these models may open new avenues for drug development.Alzheimer's Research and Therapy 05/2013; 5(3):17. DOI:10.1186/alzrt171 · 3.50 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Oligomers of beta-amyloid (Aβ) are implicated in the early memory impairment seen in Alzheimer's disease before to the onset of discernable neurodegeneration. Here, the capacity of a novel orally bioavailable, central nervous system-penetrating small molecule 5-aryloxypyrimidine, SEN1500, to prevent cell-derived (7PA2 [conditioned medium] CM) Aβ-induced deficits in synaptic plasticity and learned behavior was assessed. Biochemically, SEN1500 bound to Aβ monomer and oligomers, produced a reduction in thioflavin-T fluorescence, and protected a neuronal cell line and primary cortical neurons exposed to synthetic soluble oligomeric Aβ(1-42). Electrophysiologically, SEN1500 alleviated the in vitro depression of long-term potentiation induced by both synthetic Aβ(1-42) and 7PA2 CM, and alleviated the in vivo depression of long-term potentiation induced by 7PA2 CM, after systemic administration. Behaviorally, oral administration of SEN1500 significantly reduced memory-related deficits in operant responding induced after intracerebroventricular injection of 7PA2 CM. SEN1500 reduced cytotoxicity, acute synaptotoxicity, and behavioral deterioration after in vitro and in vivo exposure to synthetic Aβ and 7PA2 CM, and shows promise for development as a clinically viable disease-modifying Alzheimer's disease treatment.Neurobiology of aging 11/2012; 34(4). DOI:10.1016/j.neurobiolaging.2012.10.016 · 4.85 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The term 'dementia' encompasses a number of neurodegenerative diseases of which Alzheimer's disease (AD) is the most common. Prior to 2003, cholinesterase inhibitors, such as donezepil, were the only class of drugs approved to treat mild-to-moderate AD. In 2003, memantine became the first drug approved by the US FDA to treat moderate-to-severe AD. Currently, both memantine and donepezil are FDA approved for the treatment of moderate-to-severe AD. This article examines the pharmacologic profile of memantine, evidence for memantine's efficacy in moderate-to-severe AD and other dementias, its novel use in other neuropsychiatric disorders and future implications and research directions for memantine.Expert Review of Neurotherapeutics 10/2011; 11(10):1359-70. DOI:10.1586/ern.11.132 · 2.83 Impact Factor