How do Alzheimer’s medications work?

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). You’ll find a table of these medications, along with their side effects and some additional comments, at the end of this article.

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.

Medications for memory and cognitive symptoms

Generic name Brand name Side effects Comments
donepezil Aricept Nausea, diarrhea, dizziness, insomnia, vomiting, muscle cramps, fatigue, loss of appetite, weight loss Most widely prescribed drug in its class. Adverse effects are often mild and decline with continued use. Should be taken in the evening, just before going to bed. Can be taken with or without food.
galantamine Razadyne Nausea, vomiting, loss of appetite, weight loss, diarrhea, dizziness Side effects are usually gastrointestinal and occur in early weeks of treatment. Taken twice daily, with morning and evening meals.
memantine Namenda Confusion, anxiety, back pain, painful urination, cough, insomnia, irritability, nausea, nervousness, joint pain, shortness of breath Prescribed for moderate to severe Alzheimer’s disease. Tell your doctor if you have kidney disease or urinary tract problems because this drug can make these conditions worse.
rivastigmine Exelon Nausea, vomiting, loss of appetite, weight loss, dizziness, fainting, indigestion, fatigue Associated with significant nausea, vomiting, and weight loss. If you have stopped taking the drug for more than several days, don’t resume taking it without first consulting a physician.
tacrine Cognex Liver toxicity, nausea, vomiting, diarrhea, loss of appetite, muscle pain, loss of coordination, indigestion Still available, but rarely prescribed because it can cause liver damage.

Related Information: A Guide to Alzheimer’s Disease