Patients with mild or moderate Alzheimer's can get some improvement or slowing in the progression of their distressing symptoms, using drugs called cholinesterase inhibitors - examples are tacrine, rivastigmine, donepezil, and galantamine. However, to date there has not been much for the doctor to offer for patients with moderate to severe Alzheimer's. That may change in the near future. A new approach, tackling a different type of transmitter in the brain, has shown promising results. A report in the New England Journal of Medicine describes the results of a clinical study of memantine, a representative of a class of drugs called NMDA inhibitors. (NMDA stands for N-methyl-D-aspartate.)

What was done

Alzheimer's patients over 50 were recruited at 32 US clinical centers; they had to have a Mini-Mental State Examination (MMSE) score between 3 and 14, as well as other evidence of severe dementia. Those with vascular dementia or a non- cause for dementia were excluded, as well as those taking drugs for conditions like Parkinson's disease or epilepsy.

They were given either memantine or placebo (a sugar pill), randomly, in a double-blind fashion (i.e. neither the doctors nor the subjects knew who got which medication) for 28 weeks. Before, at 12 weeks, and at the end of the study there were several well-recognized tests of the degree of dementia and difficulty with activities of daily living.

What was found

There were 126 patients in both treatment groups - memantine and placebo. Their average age was 76, and two-thirds of them were women. About one in four of them dropped out of the study before 28 weeks were up, so that the average length of treatment was 24 weeks. Various reasons were given for patients leaving the study, but the numbers for each were about the same in each treatment group.

The patients given memantine had significantly better results on both the chief scales used to evaluate their dementia, as well as on one other test. The improvement was seen at 12 weeks, but was more marked at 28 weeks. There was no difference in the results between patients with different severity of dementia at the outset.

Side effects of treatment were reported by most of the patients, but these weren't severe, and they weren't related to the memantine. Agitation, urinary incontinence, urinary tract infection, insomnia, and diarrhea were all reported, but they were equally common in both the placebo and memantine groups.

What does this mean?

This study shows that a new type of drug - an NMDA antagonist - is able to improve, or at least slow the worsening of, the symptoms of severe Alzheimer disease. This represents a considerable step forward, as until now there hasn't been any effective treatment to help such patients. The doctors describing this study suggest that future trials should be done using memantine together with a cholinesterase inhibitor drug, given in combination. We can only hope that this may produce even greater improvements.

Memantine is available as Axura® in European countries. It is not yet available in the USA.