Article

Memantine for dementia

Department of Psychiatry, University of Oxford, Oxford, England, United Kingdom
Cochrane database of systematic reviews (Online) (Impact Factor: 5.94). 02/2006; 2(2):CD003154. DOI: 10.1002/14651858.CD003154.pub5
Source: PubMed

ABSTRACT Memantine, a low affinity antagonist to glutamate NMDA receptors, may prevent excitatory neurotoxicity in dementia.
To determine efficacy and safety of memantine for people with Alzheimer's disease (AD), vascular (VD) and mixed dementia.
The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was searched on 8th February 2006. This register contains references from all major healthcare databases and many ongoing trial databases and is updated regularly. In addition, the search engines Copernic and Google were used to identify unpublished trials through inspection of the websites of licensing bodies like the FDA , EMEA and NICE and of companies' websites (Lundbeck, Merz, Forest, Suntori etc) and clinical trials registries.
Double-blind, parallel group, placebo-controlled, randomized trials of memantine in people with dementia.
Data were pooled where possible. Intention-to-treat (ITT) and observed case (OC) analyses are reported.
1. Moderate to severe AD. Two out of three six month studies show a small beneficial effect of memantine. Pooled data indicate a beneficial effect at six months on cognition (2.97 points on the 100 point SIB, 95% CI 1.68 to 4.26, P < 0.00001), activities of daily living (1.27 points on the 54 point ADCS-ADLsev, 95% CI 0.44 to 2.09, P = 0.003) and behaviour (2.76 points on the 144 point NPI, 95% CI 0.88 to 4.63, P=0.004), supported by clinical impression of change (0.28 points on the 7 point CIBIC+, 95% CI 0.15 to 0.41, P < 0.0001).2. Mild to moderate AD. Pooled data from three unpublished studies indicate a marginal beneficial effect at six months on ITT cognition (0.99 points on the 70 point ADAS-Cog, 95% CI 0.21 to 1.78, P = 0.01) which was barely detectable clinically (0.13 CIBIC+ points, 95% CI 0.01 to 0.25, P = 0.03) but no effect on behaviour, activities of daily living or OC analysis of cognition.3. Mild to moderate vascular dementia. Pooled data from two six month studies indicated a small beneficial effect of memantine on cognition (1.85 ADAS-Cog points, 95% CI 0.88 to 2.83, P = 0.0002), and behaviour (0.84 95% CI 0.06 to 0.91, P = 0.03) but this was not supported by clinical global measures.4. Patients taking memantine were slightly less likely to develop agitation (134/1739, 7.7% versus 175/1873, 9.3% OR 0.78, 95% CI 0.61 to 0.99, P = 0.04). This effect was slightly larger, but still small, in moderate to severe AD (58/506 [12%] vs 88/499 [18%]; OR = 0.6, 95% CI 0.42 to 0.86, P = 0.005). There is no evidence either way about whether it has an effect on agitation which is already present.5. Memantine is well tolerated.
Memantine has a small beneficial effect at six months in moderate to severe AD. In patients with mild to moderate dementia, the small beneficial effect on cognition was not clinically detectable in those with vascular dementia and was detectable in those with AD. Memantine is well tolerated.

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    • "In fact, four of the five medications approved by the FDA for prescription to AD patients are aimed to increase extracellular levels of acetylcholine by delaying its degradation (the acetylcholinesterase inhibitors: tacrine, rivastigmine, galantamine and donepezil). The fifth approved drug is memantine, a partial antagonist for the ionotropic glutamate NMDA receptor [4]. Memantine presumably reduces calcium-mediated glutamate excitotoxicity , hence slowing synaptic and neuronal loss characteristically observed in the AD brain [5]. "
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    ABSTRACT: Alzheimer's disease (AD) is a leading cause of dementia among elderly. Yet, its etiology remains largely unclear. In this review, we summarize studies that associate systemic infection and neuroinflammation with AD, while highlighting that early-life or life-long exposure to infectious agents predisposes one to develop AD at a later age. Copyright © 2015. Published by Elsevier Masson SAS.
    Microbes and Infection 04/2015; 60(8). DOI:10.1016/j.micinf.2015.04.004 · 2.73 Impact Factor
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    • "from excitotoxicity, as a major contributing mechanism to escalating dementia [3]. According to systemic clinical studies on AD patients, Memantine improves cognition [4] and may reduce behavioral and psychological symptoms of dementia [5]. In spite of the promising results however, Memantine treatment as other currently available ones for AD (Donepezil, Rivastigmine and Galantamine) is symptomatic and does not halt the disease progression [6], the fact necessitates new drug investigations upon comprehensive knowledge of AD and accompanying dementia. "
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    • "Actually donepezil was found to be effective in patients with mild AD [22] and post-hoc subgroup analyses revealed that galantamine and rivastigmine were superior to the placebo in trial participants with the mildest disease severity [23] [24] [25]. Theoretically memantine, which reduces the excitatory toxic action of glutamate, might be neuroprotective and have maximal efficacy in the early phases of the disease; contrary to expectations , however, meta-analyses revealed larger effects in patients with greater disease severity [26] [27] [28]. In moderate to severe patients, there is general agreement about the efficacy of 20 mg/day memantine on cognition either administered alone [26, 28–30, 31] or combined with donepezil [32] [33]. "
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    ABSTRACT: BACKGROUND: Randomized clinical trials have evaluated the efficacy of acetylcholinesterase inhibitors (AChE-Is) and memantine across a wide range of Alzheimer's disease (AD) severity. However, these drugs are prescribed and reimbursed according to precise upper and lower cut off scores of cognitive tests. OBJECTIVES: To verify whether the efficacy of pharmacological treatment had any dependence on the severity of dementia in AD patients. METHODS: Published English-language randomized, placebo-controlled trials evaluating the efficacy of AChE-Is or memantine at any dose, over any length of time, in patients with any severity of dementia due to AD were included. Cognitive, behavioral, and functional outcomes were extracted from each study and multiple outcomes from the same trial were pooled to obtain a unique indicator of efficacy for cognition, functional impairment, and behavioral and psychological disturbances. The existence of a relationship between size of the treatment effect and severity of dementia, measured with the Mini-Mental State Examination, was determined using parametric and non-parametric correlation analyses. RESULTS: Both AChE-Is and memantine had significant effects on cognition. Functional and psycho-behavioral outcomes were reported less frequently but also showed significant efficacy of treatment. High heterogeneity among studies was found within and between the different drugs. The efficacy of all drugs except memantine was independent from dementia severity in all domains. Memantine effect on functional impairment was better in more severe patients. CONCLUSIONS: The modest beneficial effects of anti-dementia drugs on cognition are independent from dementia severity. Memantine is more effective on functional incompetence only in severe patients.
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