Memantine for dementia.
BACKGROUND
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.


OBJECTIVE
To determine the clinical efficacy and safety of memantine for people with Alzheimer's disease, or vascular or mixed dementia.


METHODS
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.


METHODS
Double-blind, parallel group, placebo-controlled, randomised and unconfounded trials in which memantine was administered to people with dementia.


METHODS
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.


RESULTS
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.


CONCLUSIONS
: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.
Areosa Sastre
A
A
McShane
R
R
Sherriff
F
F
D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy; D003072:Cognition Disorders / Q000188:drug therapy; D003704:Dementia / Q000188:drug therapy*; D015140:Dementia, Vascular / Q000188:drug therapy; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D006801:Humans; D008559:Memantine / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
D018691:Excitatory Amino Acid Antagonists; D008559:Memantine