The low affinity glutamate NMDA receptor antagonist memantine can slightly reduce deterioration in patients with moderate to severe Alzheimer’s disease, but the effect in less severely affected people is unknown.
Alzheimer’s disease is found in over 50% of people with dementia at autopsy. It is the commonest single cause of dementia affecting some 2% of people aged 65 with the prevalence doubling every five years to at least 90 years of age. As more is understood about the disease, drugs have been introduced that aim to enhance nerve activity in the brain.
One option is to target the part of central nervous system activity driven by the neurotransmitter L-glutamate. This amino acid plays a key role in normal brain function, especially the formation and reinforcement of memories. In Alzheimer’s disease, nerve cells can become overactive to the point where they die. Consequently there is the hope that memantine, which blocks some of L-glutamate’s receptors, may reduce symptoms of dementia.
Cochrane Review Authors concluded that, compared to placebo, giving 20 mg/day memantine reduced symptoms in people with moderate to severe Alzheimer disease. After six months, patients given memantine had slightly less functional and cognitive deterioration and were less likely to have become agitated. However, for patients who had already developed agitation, evidence of any effect of the drug was absent. It was impossible to say anything definite about whether memantine is useful in less severe Alzheimer’s disease.
The reviewers also looked to see if memantine could help people with vascular dementia. Although it seemed to help reduce cognitive deterioration, the effect was not big enough to be apparent to the doctors treating the patients, and was possibly more short-lived than in Alzheimer’s disease.
In both diseases memantine was well tolerated with few recorded adverse events.
Rupert McShane, one of the co-authors said: “This is the only treatment licensed for more severe Alzheimer’s disease, so there is little doubt that it is a useful advance. The problem is that its effect is small. And we’re worried that one of the most important studies has still not been published. This sort of delay usually means that the results were not so good, and if that study found a very different result from the others it could change our conclusions.”
“Whether the drug is good enough for health services to buy is a moot point. The National Institute for Clinical Excellence in the UK has suggested that it might not be, but there’s not much data to go on and there’s no doubt that if we really want to know whether it’s cost-effective we need to do a larger and longer randomised trial measuring quality of life in a way which everyone can agree is sensible. Unfortunately, when effective drugs are not publicly funded it inevitably creates a two-tier service because only those who can afford to pay privately can be prescribed the drug,” says McShane.