facts for health--alzheimer's--frequently asked questions

In general, cholinesterase inhibitors are the first-line medication treatments for Alzheimer's disease, because they show the strongest evidence for benefit and tolerability. Donepezil is approved for mild to moderate AD and for severe AD, while the others are approved for mild to moderate AD. Memantine is currently approved for only moderate to severe AD. Other treatments with less evidence supporting their benefit and safety in treating Alzheimer's disease may also be tried based on patients' needs and medical history.

Other medicines may be beneficial for treating behavioral disturbances of patients with Alzheimer's disease. Antidepressants, antipsychotics and anticonvulsants may all be employed both for the specific indications implied in their names and for other more general beneficial effects. There is some chance that antipsychotic drugs may increase the risk of death when used in people with AD.

Do Alzheimer's disease medications make a worthwhile difference?

Alzheimer's disease (AD) medications can slow the progression of AD and sometimes are associated with actual improvement in thinking, memory and behaviors. However, some Alzheimer's disease sufferers do not benefit from or may not tolerate cholinesterase inhibitors or memantine. In other patients, the benefit may be slight or only recognized when discontinuation of an effective medication leads to more rapid progression of the underlying AD.

Antidepressants, antipsychotics and anticonvulsants may be very helpful in alleviating distressing disorders that can accompany and complicate treatment of Alzheimer's disease. There is concern that antipsychotic drugs may increase the risk of death when used in people with AD.

Are any of the Alzheimer's disease medications addictive?

What does my clinician need to know to prescribe medication for Alzheimer's disease?

Your clinician will need to know your family and personal medical and psychiatric histories, other medications you are taking and your current activities. Medication interactions are an important consideration, so be sure to inform your clinician of every medication you take, including over-the-counter medications and herbal remedies. Your activities are important because certain medications may make it harder for you to carry them out safely.

The main point is to inform your clinician about all medical and psychiatric conditions and medications, especially if you are being treated by several clinicians. If you are not sure whether certain facts should be brought out, mention them and let your clinician decide how important they are. Without such information, a clinician would have difficulty treating you safely and effectively.

Do I need any tests before starting medication?

Laboratory tests may or may not be necessary before starting medication therapy. Depending on your medical history and the medication you will use, your clinician may want you to have some blood tests and an electrocardiogram (ECG or EKG).

Which Alzheimer's disease medication should I start on?

The choice of a specific medication is something for you and your clinician to decide, based on a number of factors. In general, FDA-approved cholinesterase inhibitors are tried first, and more than one of them may be tried before moving to other classes of medications. How much you benefit and how well you tolerate a medication are important in deciding whether to continue that medication or switch to another medication. For patients with moderate to severe AD, donepezil or memantine may be selected first.

Will I get more benefit if I take two or more of these medications together?

One well-designed research study found that adding memantine to donepezil was beneficial. It is also standard practice for many doctors to combine cholinesterase inhibitors and vitamin E, although more recently vitamin E has fallen out of favor as a treatment.

How do medications work in Alzheimer's disease?

Cholinesterase inhibitors slow the breakdown of acetylcholine, an important neurotransmitter involved in thinking and memory. Alzheimer's disease causes several brain abnormalities. One of them is a progressive decrease in the acetylcholine neurotransmitter (brain messenger) system functioning. It's as though an engine — in this case the brain - is being starved of fuel and not firing all cylinders. Cholinesterase inhibitors increase acetylcholine and permit more neurotransmission. By analogy, the engine would no longer be as starved for fuel and would then be able to fire more of its cylinders. This description is obviously an oversimplification of Alzheimer's disease, as other neurotransmitters are also involved.

Memantine's action differs from the cholinesterase inhibitors. It is a partial NMDA receptor blocker and appears to work by restoring a proper balance in the glutamate-NMDA system. NMDA is an easier to remember abbreviation for N-methyl-D-aspartate. NMDA receptors are heavily concentrated in the cortex (outer layer of the brain) and in the hippocampus, where they play important roles in learning and memory. Both cortex and hippocampus are damaged in AD.

Glutamate is the major excitatory or accelerator neurotransmitter in the brain. Important in learning and memory, glutamate speeds brain functions mainly through stimulating NMDA receptors. Too much stimulation may damage neurons and chronic over-stimulation may lead to death of neurons (neurodegeneration). Some NMDA receptor blockers (antagonists) have been shown to prevent neuron injury. However, the balance of neuron stimulation and inhibition is delicate and too much blockade of glutamate also causes mental problems.

How rapidly do medications work in Alzheimer's disease?

When cholinesterase inhibitors work in Alzheimer's disease, improvement is often gradual and subtle. Ideally, improvement in memory, thinking and behaviors would be rapidly and readily apparent. More often, however, benefit is measured by stabilization of these functions and a subsequent slowing of their loss. If deterioration is obvious despite use of an appropriate medication, a difficult decision must be made. It is possible that deterioration will accelerate after stopping the medication. Experts often advise that patients should have at least a 6-month trial on a therapeutic dose of medication. If the patient still declines more than expected during treatment, another intervention should be considered. Other interventions to consider are a dose adjustment, changing to another medication or adding memantine or an experimental medication. If the clinician, patient and family decide to try another drug, the switch should be made rapidly. Usually when switching there are no days completely off medication and an effort is made to build up to a therapeutic dose of the new medication as soon as possible. If the patient worsens during the switchover, a return to a therapeutic dose of the first drug is warranted.

How are Alzheimer's disease medications handled in the body?

When taken by mouth, cholinesterase inhibitors are absorbed into the blood stream and carried to all body tissues, including the brain. Cholinesterase inhibitors are gradually eliminated from the body after being broken down (metabolized) by the liver and kidneys. Since the liver is the main organ of medication metabolism, diseases or medications affecting the liver may change medication metabolism but rarely necessitate adjustment of dose. As people grow older, they also metabolize medications more slowly. While about one-third of memantine is metabolized before excretion, most is excreted unchanged in the urine.

How should I store Alzheimer's disease medication?

Keeping a current week's supply in a plastic container divided into daily compartments can help you remember to take your medication on schedule. The rest should be stored in the original prescription containers, away from sources of heat or moisture and out of contact with direct sunlight. Do not store Alzheimer's disease medication in the bathroom medicine cabinet where heat and moisture may cause it to break down. All Alzheimer's disease medications in large amounts are potentially poisonous, so they must be kept out of reach of children. Be sure to discard medication that is outdated or not needed. Since some of this information may be hard to remember, you may want your caregiver to take charge of all your medicines, including your AD medication.

What if I am running out of medication?

If you are close to running out of medication, contact your clinician immediately to arrange to get more. In order to be effective, Alzheimer's disease medications must maintain a certain blood level. That is why they are not prescribed on an "as needed" basis. Also, if you plan to stop taking Alzheimer disease medication, it is usually a good idea to discontinue the medication slowly to make it easier for your body to adjust. A decision to stop treatment should be discussed with your clinician.

What if I forget a dose?

Since problems remembering things is a symptom of Alzheimer's disease, medication doses may be forgotten. Help from a caregiver is valuable, but even caregivers can forget. Dosage schedules vary, so it is important to ask your clinician what to do if you forget a dose. Until you have done this, safe rules to follow are:

Can AD medications be used safely in people with heart or blood pressure problems?

Cholinesterase inhibitors can slow the heart rate, although the degree of slowing is not usually important. Rarely, enough slowing can occur to cause a person to feel dizzy or even black out (a syncopal episode). This may be more likely to happen if someone already has heart disease. In general, these medications do not cause major changes in blood pressure. Memantine has no known effects on the heart.

Before prescribing an Alzheimer's disease cholinesterase inhibitor, your doctor will want to know about your medical history including any problems with your heart.

Is it dangerous to take other medications with Alzheimer's disease medication?

Elderly individuals often have medical problems and this is true for most patients with Alzheimer's disease (AD). Commonly, other medications are being taken and some medication combinations may be dangerous.

It is best to ask your doctor for a specific recommendation. Most medications can be taken safely with AD medications. Some, however, may interact with AD medicines in such a way as to cause serious side effects. Therefore, it is best to tell all doctors treating you that you are taking AD medications. Before taking any medication (prescription or nonprescription, including herbal and nutritional supplements), ask your doctor or pharmacist whether it might interact adversely with your AD medication.

Will Alzheimer's disease medications interfere with my sexual drive and orgasm?

Very little information is available. Interest in sex may increase or decrease as may ability to perform sexually. Most often there is no effect on sexual functioning, although certain antidepressants can cause problems. The physician should be notified if sexual problems occur, as causes other than Alzheimer's disease and its treatment may explain the sexual problem.

Can I exercise while taking Alzheimer's disease medications?

By all means! Appropriate regular exercise is a healthy activity for people of all ages and recent research suggests exercise can improve brain functioning in older adults. We do not know if exercise will slow the progression of Alzheimer's disease, but it may help prevent the onset of AD. Medical conditions may determine the kinds and extent of exercise that are appropriate for you.

How long should I take medication for Alzheimer's disease?

If cholinesterase inhibitors have a beneficial effect, they should usually be continued long-term. Unfortunately, when effective cholinesterase inhibitors have been discontinued, the underlying Alzheimer's disease appears to have been smoldering along under the cover of the effective medication. Without that effective medication, rapid deterioration often occurs. Benefits of continued cholinesterase inhibitor treatment have been observed for as long as several years in some patients.

There is less information regarding the long-term use of memantine. From studies where patients could continue to take the drug after the study was over, there is evidence that the benefits persist for at least a year in those who continue to take the medication. We do not know how long benefits persist, or whether there is prominent deterioration if the memantine is stopped.

What if the Alzheimer's disease medication I am taking doesn't work?

It is important to make sure the dose is adequate and that expectations are realistic. A drug may "work" by stabilizing your condition without any visible improvement. So at least a several month trial at a therapeutic dose is necessary. It is possible that a person who does not respond to one Alzheimer's disease medication may respond to a different medication. If FDA-approved Alzheimer's disease medications are ineffective, trials of other medications that have been shown to be effective in carefully conducted random-assignment, placebo-controlled, double-blind studies may also be appropriate. Vitamin E, selegiline and Ginkgo biloba all have evidence supporting their benefit in some individuals, although their value remains controversial. Some doctors may recommend starting these medications in combination with the FDA-approved cholinesterase inhibitors.

Are there any new medications for treating Alzheimer's disease?

Rachelle S. Doody, M.D., Ph.D.

Dr. Rachelle S. Doody has written over 100 publications, most of which deal with the diagnosis and treatment of Alzheimer's disease and related disorders. She has received many grants supporting research on Alzheimer's disease. She participates in national and international studies and in review and advisory boards. Currently, Dr. Doody is the Effie Marie Cain Professor in Alzheimer's Disease Research at Baylor College of Medicine, Houston, Texas. A leading authority, Dr. Doody had this to say about new medications:

"Several types of drugs are being developed to treat Alzheimer's disease. Some of these new potential therapies are drugs that are already in use for other disorders, such as diabetes and hypercholesterolemia. Others are based upon nutraceuticals, or naturally occurring substances, like the antioxidant resveratrol in red grapes, or DHA, an omega 3 fatty acid found in fish oil. Some of the drugs under development affect transmitter systems in the brain. Although currently approved therapies also affect transmitter systems, most of the ones under development target different neurotransmitters, and some of them also show neuroprotective actions in test tube experiments."

"Because amyloid protein fragments always build-up in the brains of Alzheimer's disease patients, several approaches to preventing or reversing this build-up are under development. These include enzyme blockers (beta and gamma secretase inhibitors, including the drug flurizan), agents that try to block the deposition of amyloid or dissolve the build-up (e.g. scyllo-inositol or TTP488) and immune strategies to stimulate the immune system and clear out the amyloid plaque. The first human vaccine studies, with an agent known as AN-1792, had to stop because a small percentage of patients developed brain inflammation. Other immunotherapies are now being developed to try and avoid this side effect, such as bapineuzamide, a passive antibody that is given intravenously and directed against amyloid protein in the brain."

Which medication is best?