Summary

Doctors' groups have carried out a review of the five drugs approved for the treatment of Alzheimer's disease. Though trials show statistically significant improvements in cognitive function, these do not translate into meaningful benefits for people with dementia or their carers. Therefore, these medications should not be prescribed routinely, but on the basis of individual assessments. Much more needs to be done to find effective therapies for Alzheimer's disease.

Introduction

The prevalence of Alzheimer's disease, the most common form of dementia, will quadruple during the next 50 years as the 'baby boomer' generation starts to age. There is no cure, although many research groups around the world are looking at new approaches to preventing, slowing or reversing the brain damage associated with the disease. There are five drugs approved by the United States Food and Drug Administration (FDA) for the treatment of the symptoms of dementia. Four are classed as cholinesterase inhibitors: donepezil, galantamine, rivastigmine and tacrine. The latter has fallen into disuse because it has severe side effects. They increase levels of choline, a brain chemical involved in memory and learning. A fifth drug, memantine, acts by blocking the NMDA receptor in the brain and is used in more severe cases of dementia.

People with dementia and their carers are anxious to have help in controlling memory decline and the other distressing manifestations of this disease. So these drugs are much in demand and, indeed, sales were worth nearly $3 billion in 2007 with donepezil and memantine accounting for most of the money spent. But how good are they, really? The American College of Physicians and the American Academy of Family Physicians has carried out a review of the evidence on these five drugs.

What was done

The review looked into 59 studies of the five medications. The researchers found that many studies used different scales to measure the drugs' impact upon cognition, behavior, and overall functioning. There were no head-to-head trials comparing the drugs with one another.

What was found

Trials showed statistically significant improvements in areas such as memory, the researchers say. But these outcomes were not clinically meaningful. Overall, taking one of these five drugs does not lead to improvements in the patient's ability to manage every day activities. Of course, there will be individuals who benefit greatly from these medications but the doctors' organizations now say that they cannot be recommended as the standard of care for someone with dementia. The option to prescribe them must be there, but the physician must take a case-by-case approach.

What this study means

This review has exposed the unsatisfactory nature of treatment for dementia at the current time. The available drugs do not seem to offer any particular benefit and, indeed, they may offer none at all. There seems to be no reason for preferring one drug to another, because head-to-head trials have not been done. The doctors call for such trials to be carried out so the physician and patient can make a more informed choice about these medications. Nor is there any information about how long the medications should be taken for, or which sub-groups of patients might have most to gain from taking them. Again, the relevant studies need to be carried out. Most of all, there is an urgent need for new therapies for Alzheimer's and other forms of dementia - drugs that will actually alter the course of the disease, rather than just treating the symptoms. Trials are underway on vaccines, antibodies and other new approaches. Positive results are needed, and they cannot come soon enough.