Alzheimer's drugs target symptoms, not underlying causes

DEAR DOCTOR K: Can you tell me about medications to treat Alzheimer's disease? How do they work, and what do they do?

DEAR READER: The drugs currently available to treat Alzheimer's disease target the symptoms, but not the underlying causes of the disease. The memory loss, impaired thinking and personality changes seen in Alzheimer's disease come from a loss of neurons (nerve cells) and their connections with other neurons. The symptoms of Alzheimer's disease also come from a decline in levels of neurotransmitters - brain chemicals that carry messages between nerve cells.

Currently, no treatment prevents or stops Alzheimer's. However, medications can improve symptoms in many patients, although only temporarily.

The FDA has approved five drugs for the treatment of Alzheimer's disease: donepezil (Aricept), rivastigmine (Exelon), galantamine (Razadyne, formerly Reminyl), tacrine (Cognex) and memantine (Namenda). I've put a table of these medications, along with their side effects and some additional comments, on my website, AskDoctorK.com.

In some people, these drugs lead to modest improvements in memory and cognitive function (such as making decisions and exercising judgment).

Donepezil, rivastigmine, galantamine and tacrine belong to a class of drugs called cholinesterase inhibitors. They raise the levels of acetylcholine in the brain. (A deficiency in this neurotransmitter contributes to the memory problems of this disease.) The drugs are effective for people with mild to moderate Alzheimer's disease.

Memantine works differently. It blocks glutamate, another neurotransmitter. This is beneficial because too much glutamate can destroy neurons.

Other drugs are used to treat emotional and behavioral problems that often arise in people with Alzheimer's disease. These include antidepressants, anti-anxiety drugs and antipsychotics.

In addition to relieving depression, antidepressants often enhance the social functioning in a person with Alzheimer's disease. They may improve appetite and sleep and increase energy, too.

Anti-anxiety drugs may help a person with Alzheimer's disease who is anxious, restless or agitated. Because they are also sedating, these medications often relieve insomnia and sundowning. (That's the worsening of behavior problems in the evening.)

Antipsychotic drugs may help manage behavior problems that result from delusions, hallucinations, paranoia, severe agitation and hostility.

Will there ever be treatments that can prevent Alzheimer's disease, or that can reverse the disease once it starts? I am cautiously optimistic. Over the past 25 years, enormous progress has been made in understanding what causes Alzheimer's disease, much of it from colleagues of mine here at Harvard Medical School.

Two molecules, called amyloid beta and tau, begin accumulating in the brain many decades before the symptoms begin. By measuring these molecules, doctors may be able to identify the people who are at risk for getting Alzheimer's disease decades before the symptoms start.

We now have treatments that reduce the levels of amyloid beta. They have not worked yet in humans who already have the disease. However, many experts think that the treatments may work better if started years before the symptoms of the disease appear in people at high risk. It will take a decade or more to know.

Dr. Komaroff is a physician and professor at Harvard Medical School. To send questions, go to AskDoctorK.com, or write: Ask Doctor K, 10 Shattuck St., Second Floor, Boston, MA 02115.