Medications and Treatment

Although currently there is no drug that can cure Alzheimer's disease, families need to consider several options in the ongoing treatment of the person with Alzheimer's disease. The Primary Care physician should be intricately involved in making recommendations about medications that may slow or temporarily delay the cognitive symptoms of the disease. Additionally, if the are medical or behavioral symptoms that are treatable, such as depression or agitation, options are available that may provide relief for the patient and allay some of the difficulties the family members deal with on a daily basis.

Families may also want to consider non-traditional forms of treatment that may involve anti-oxidants, massage, art and other therapeutic mediums, among others. Involving the patient in regularly scheduled and routine activities may also provide continuity and allow the patient to function more independently for a longer period of time. Environmental concerns as well as the physical needs are all to be considered the treating the person with Alzheimer's disease.

 

Drug Support & Therapy Index
-Aricept (Donepezil Hydrochloride)	-Non Steroidal Anti-Inflammatory Drugs (NSAIDs)
-Exelon (rivastigamine)	-Vitamin E
-Reminyl (Galantamine)	-Selegiline (also known as Deprenyl or Eldepryl)
-Cognex (tetrahydroaminoacridine, tacrine, or THA)	-Hormone Replacement Therapy
-Memantine	-Ginkgo biloba

  There currently are four medications approved by the U.S. Food and Drug Administration to specifically treat Alzheimer's disease: Aricept, Exelon, Reminyl and Cognex. The advantages to having four medications are obvious. Each of the approved drugs may have different side effects for individual people taking the medication. Having more approved drugs offers doctors, people with the disease and their families a greater opportunity to find the one that will offer some benefit with the fewest unwanted side effects. Please note: The Alzheimer's Association does not recommend switching from one of these medications to another if the current medication has been well tolerated and some benefits have been indicated.

Facts About Aricept (Donepezil Hydrocloride) and Alzheimer's Disease

What is Aricept?
Aricept is the second drug approved by the U.S. Food and Drug Administration specifically to treat Alzheimer's disease. It is not a cure for Alzheimer's disease, nor does it stop the progression of the disease.

How does Aricept work?
Aricept is a specific inhibitor of an enzyme called acetylcholinesterase. In the brain, acetylcholinesterase limits the amount of acetylcholine, a neurotransmitter involved in nerve cell communication. Research has shown that there is not enough acetylcholine in the brains of individuals with Alzheimer's disease; by inhibiting the enzyme that breaks down acetylcholine, it is hoped that higher concentrations of intact acetylcholine will remain in the brain. Increasing the concentration of acetylcholine in the brains of individuals with Alzheimer's disease may increase communication between nerve cells, and in turn, temporarily improve the symptoms of the disease.

Is Aricept effective in all individuals with Alzheimer's disease?
Aricept is indicated for the treatment of mild to moderate Alzheimer's disease. Because of the declining number of functional nerve cells present in the brain as the disease progresses, this drug may not be as effective for individuals in the advanced stages of the disease. No differences in the effectiveness of Aricept were observed based on the age, sex, and race of the individuals who were treated during clinical trials.

What is the daily dosage of Aricept?
Aricept is administered once or twice daily and can be taken with or without food. It is available in 5mg or 10mg tablets, and the prescribed dosage should be determined by a physician.

What are the side effects of Aricept?
The most frequent side effects of Aricept include diarrhea, nausea, and vomiting, insomnia, fatigue, and anorexia. In most cases, these side effects were observed to be mild, usually lasting from one to three weeks and declining with continued use of the drug. Whenever a person begins taking a new drug, the doctor, patient, and family member(s) should discuss what the potential side effects may be, and how the drug may interact with other prescription or over-the-counter drugs that are being taken.

How and where can you get Aricept?
Aricept is available only by prescription from your doctor. Because there is no known way to predict whether or not an individual with Alzheimer's disease will benefit from the use of Aricept, it is important to have a thorough discussion with your doctor about the possible results of treatment with this drug. Through this discussion, you and your doctor can weigh the possible benefits, risks, and costs associated with Aricept in order to decide whether or not to try it.

What kinds of questions should you ask your doctor?
What are the potential benefits of taking Aricept? How long should the person take Aricept before a response can be detected? How often is Aricept administered to individuals with Alzheimer's disease? What should I do if the person misses taking a dose of Aricept? What are the known side effects of Aricept? If the person has side effects can I stop the drug immediately? If the drug is stopped suddenly, what happens to the patient? What drugs (prescription and over-the-counter) might interact with Aricept? How might Aricept affect other medical conditions? What changes in the patient's condition should be reported immediately? How often will the patient have to visit the clinic? Can an Alzheimer patient in a nursing home take Aricept? What are the costs associated with taking Aricept?

What other things can be done to improve the patient's and family's experience with Alzheimer's disease?
Through their collective experience, families and professional caregivers have developed a wide range of strategies to help manage symptoms of Alzheimer's disease, and to help reduce the impact this disease has on everyone affected. Such strategies include environmental and behavioral modifications, activity programs, and support and respite services.

This fact sheet is provided for your Information only, and does not represent an endorsement of donepezil hydrochloride by the Alzheimer's Association.

Facts about Cognex and Alzheimer's Disease

What is Cognex?
Cognex (also called tetrahydroaminoacridine, tacrine, or THA) is the first drug approved by the U.S. Food and Drug Administration specifically to treat Alzheimer's disease. It is not a cure for Alzheimer's disease, nor does it appear to stop the progression of the disease. Cognex is made by ParkeDavis, a division of the WarnerLambert Company.

How does Cognex work?
The billions of nerve cells in the brain communicate using chemicals. In Alzheimer's disease, nerve cells in regions of the brain responsible for memory and other thought processes degenerate for unknown reasons. Some of the most severely affected nerve cells communicate using a chemical called acetylcholine.

Normally, acetylcholine is produced by nerve cells, released, and then broken down. Cognex slows the breakdown of acetylcholine, which increases the amount of acetylcholine present in the brain. Since the amount of acetylcholine is decreased in the brains of patients with Alzheimer's disease, increasing the amount of this chemical may enable nerve cells to communicate better. This, in turn, may relieve some of the memory impairment and other symptoms associated with Alzheimer's disease.

Is Cognex effective in all Alzheimer patients?
From what is currently known, Cognex will not improve the condition of the majority of Alzheimer patients. To date, Cognex has only been studied in patients who had Alzheimer's disease of mild to moderate severity and otherwise were in generally good health. There is no known way to predict whether or not Cognex will help an Alzheimer patient. The only way to determine what effects Cognex will have on any individual patient is for the patient to try the drug.

What are the side effects of Cognex?
The most common side effect of Cognex is an increase in a particular liver enzyme (alanine aminotransferase, or ALT). Once again, there is no way to predict before trying the drug whether any individual patient will experience this side effect. When a patient starts taking Cognex, blood will be drawn on a regular basis to measure liver enzymes. Through regular monitoring, the doctor will learn whether the patient shows this sensitivity, and will be able to make treatment decisions accordingly.

Other side effects of Cognex may include nausea, vomiting, diarrhea, abdominal pain, indigestion, and skin rash. Any time a person begins taking a new drug, the doctor, patient, and family member(s) should discuss what potential side effects the drug may have, and how the drug may interact with other drugs being taken (prescription or overthecounter).

How can a patient get Cognex?
Cognex is available by prescription from your doctor. Due to concerns over side effects, dosage and monitoring challenges and the availability of three other similar medications, Cognex is not often prescribed. Because there is no known way to predict whether any individual Alzheimer patient will experience beneficial effects or side effects, it is important to have a thorough discussion with your doctor about the possible results of treatment with Cognex. Through this discussion, you and your doctor can weigh Cognex's possible benefits, risks, and costs in order to decide whether or not to try it.

What kinds of questions should you ask your doctor?
What are the potential benefits of taking Cognex? What are the known side effects of Cognex? What are the costs associated with taking Cognex? What drugs (prescription and nonprescription) might interact with Cognex? How might Cognex affect other medical conditions? How will we know if Cognex is working? What changes in the patient's condition should be reported immediately? How often will the patient have to visit the clinic?

What other things can be done to improve the patient's and family's experience with Alzheimer's disease?
Through their collective experience, family and professional caregivers have developed a wide range of strategies to help manage symptoms of Alzheimer's disease, and to help reduce the impact of this disease on the family. Such strategies include environmental and behavioral modifications, activity programs, support and respite services, and others.

For further information about these approaches, and about resources in your community, contact your local chapter of the Alzheimer's Association. To find out which of the Association's 221 chapters is nearest to you, please call 800-272-3900.

In order to find out whether your insurance company will pay for the costs associated with taking Cognex, contact your company's representative.

This fact sheet is provided for your information only, and does not represent an endorsement of Cognex by the Alzheimer's Association.

Promising Studies to Prevent, Delay or Treat the Symptoms of Alzheimer's Disease

Are there other drugs available to treat symptoms of Alzheimer's disease?
There are several experimental drugs being studied for the treatment of Alzheimer's disease at study sites nationwide. To obtain further information on these drugs and current clinical studies, please contact the Greater San Francisco Bay Area Alzheimer's Association 650/962-8111 or (in the Bay Area) 800/660-1993 and ask for the drug fact sheets. For local study information refer to the research section of this web site. (Current Research Opportunities)

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Facts About Memantine

What is memantine?
Memantine is a drug approved in October 2003 by the U.S. Food and Drug Administration (FDA) for treatment of moderate to severe Alzheimer’s disease. Forest Laboratories Inc., memantine’s U.S. developer, will market the drug under the trade name Namenda. Memantine was first approved in Germany for treatment of various neurological disorders in 1982, where it is marketed by Merz + Co. as Axura. Since 2002, it has been approved in the rest of the European Union, where it is marketed by Lundbeck asEbixa.

Forest announced availability of memantine in U.S. pharmacies in January 2004.

What kind of drug is memantine?
Memantine is classified as an uncompetitive low-to-moderate affinity N-methyl-D-aspartate (NMDA) receptor antagonist, the first Alzheimer drug of this type approved in the United States. It appears to work by regulating the activity of glutamate, one of the brain’s specialized messenger chemicals involved in information processing, storage, and retrieval. Glutamate plays an essential role in learning and memory by triggering NMDA receptors to allow a controlled amount of calcium to flow into a nerve cell, creating the chemical environment required for information storage.

Excess glutamate, on the other hand, overstimulates NMDA receptors to allow too much calcium into nerve cells, leading to disruption and death of cells. Memantine may protect cells against excess glutamate by partially blocking NMDA receptors.

Memantine’s action differs from the mechanism of the cholinesterase inhibitors that were previously approved in the United States for treatment of Alzheimer symptoms. Cholinesterase inhibitors temporarily boost levels of acetylcholine, another messenger chemical that becomes deficient in the Alzheimer brain.

What is the evidence that memantine may help Alzheimer symptoms?
Forest submitted evidence in support of memantine’s effectiveness in treating moderate to severe Alzheimer’s disease in a new drug application to the FDA in December 2002, amended in January 2003. In September 2003, the FDA’s Peripheral and Central Nervous System Drug Advisory Committee met to respond to specific questions raised by the FDA regarding application data. Briefing documents and summaries of advisory committee critiques are available on the FDA Web site at

http://www.fda.gov/ohrms/dockets/ac/cder03.html#PeripheralandCentralNervousSystemDrugs. At the conclusion of its meeting, the advisory committee voted unanimously that the following data submitted in the new drug application support the safety and effectiveness of memantine in treating moderate to severe Alzheimer’s disease:

1. A 28-week U.S. study enrolling 252 individuals with moderate to severe Alzheimer’s disease and initial scores ranging from 3 – 14 on the Mini-Mental State Examination (MMSE). In this double-blind study, participants were randomly assigned to receive either 10 mg of memantine twice a day or a placebo. Those receiving memantine showed a small but statistically significant benefit in a test of the their ability to perform daily activities and on the Severe Impairment Battery, a test designed to measure cognition in profoundly incapacitated individuals. On the Clinician Interview-Based Impression of Change Plus Caregiver Input, a measure of overall function, memantine recipients also showed a benefit that was significant in one analysis but not in another. In this study, when participants with MMSE scores of less than 10 were considered as a separate group, memantine recipients showed no benefit compared to those who received placebo on either daily activities or overall function.
2. A 24-week U.S. study enrolling 404 individuals with moderate to severe Alzheimer’s disease and initial MMSE scores from 5 – 14 who had been taking donepezil (AriceptÆÊ) for at least six months, with a stable dose for at least three months. In this double-blind study, participants were randomly assigned to receive either 10 mg of memantine twice a day or a placebo in addition to their donepezil. Those receiving memantine showed a statistically significant benefit in performing daily activities and on the Severe Impairment Battery, while participants taking donepezil plus placebo continued to decline.

Some advisory committee members considered memantine’s effect modest, similar in scope to the effect seen with cholinesterase inhibitors.

The advisory committee found problems with the design of a third submitted study, conducted in Latvia, because it enrolled individuals with vascular dementia as well as Alzheimer’s disease. An additional issue was that although the data showed a positive effect for memantine on reducing dependence on care, the study lacked an acceptable measure of effect on cognitive function. According to current FDA standards, drugs approved specifically to treat Alzheimer’s disease must show a benefit on cognitive symptoms as well as on overall function, which confirms that the effect on cognition is clinically meaningful.

In June 2003, Forest reported preliminary results from another add-on therapy trial enrolling participants with mild to moderate Alzheimer’s who were also taking any of three commonly prescribed cholinesterase inhibitors—donepezil (Aricept), galantamine (Reminyl), or rivastigmine (Exelon). Data from this trial were not included in the new drug application seeking approval of memantine for moderate to severe disease. According to the company, the data showed that participants receiving memantine in combination with a cholinesterase inhibitor did not experience significantly greater benefit in cognition or overall function than those who received a cholinesterase inhibitor and a placebo. These preliminary results suggest that memantine may not be as effective in individuals with mild to moderate Alzheimer’s who are taking a cholinesterase inhibitor as it may in more severely ill individuals. This data has not yet been peer reviewed or presented in a professional forum.

How is memantine supplied and prescribed?
Memantine is supplied as an oral medication in 10 mg tablets. Forest is providing prescribing information at www.namenda.com or by calling 1.877.2-NAMENDA (1.877.262.6363). Adverse effects occurring more commonly with memantine than with placebo included headache, constipation, confusion, and dizziness.

Where can I get more information?
The Alzheimer’s Association will update this fact sheet as more information becomes available from recent clinical trials or from postmarketing experience with memantine. The latest version of this fact sheet is always available on our Web site at www.alz.org or by calling our 24/7 Contact Center at 800.272.3900. You may also call Forest directly at 800.678.1605 and ask for the Professional Affairs Division.

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Facts About Non Steroidal Anti-Inflammatory Drugs (NSAIDs) and Alzheimer's Disease

What are NSAIDs?
NSAIDs are nonsteroidal antiinflammatory drugs, such as ibuprofen and aspirin, that are commonly used for the temporary relief of aches, pains, and fever. Frequently used NSAIDs are available overthecounter (e.g., Advil's, and Motrin), while others are available by prescription only.

How are NSAIDs related to Alzheimer's disease?
Researchers are still investigating the exact cause(s) of Alzheimer's disease. One avenue of research has shown that inflammation in the brain may play a role in the development of Alzheimer's. Because NSAIDs help decrease inflammation in the body, researchers believe that NSAIDs may aid in preventing or delaying the onset of Alzheimer's disease by decreasing inflammation in the brain.

What studies have been done using NSAIDs to prevent or delay the onset of Alzheimer's?
Thus far, there have been no known studies testing NSAIDs directly as a preventative treatment for Alzheimer's disease. However, promising results from a recent study led by Walter F. Stewart, Ph.D., M.P.H., at Johns Hopkins School of Medicine, show that certain NSAIDs may have a protective effect against Alzheimer's disease.

This study involved a group of participants from the Baltimore Longitudinal Study of Aging (BLSA). The BLSA is an ongoing study conducted by the National Institute on Aging that has been recruiting and evaluating volunteers from the Baltimore/Washington area since 1958. Participants in this study are evaluated every two years (through neurological and neuropsychological testing and physical examinations) and asked to list all medications used since their previous visit.

Dr. Stewart's team studied 1,686 individuals who were actively involved in the BLSA study between 1980 and 1995. Of this group, 81 individuals were diagnosed with Alzheimer's disease at some point during followup evaluations. After statistically analyzing the data obtained from the participants, Dr. Stewart's team found that individuals who used NSAIDs (more specifically, ibuprofen) at varying dosages were at a lower risk for Alzheimer's disease. Also, it was determined that the relative risk of Alzheimer's disease decreased as the duration of NSAID use increased.

Although aspirin is also an antiinflammatory, researchers found no association between use of aspirin and lowered risk of Alzheimer's disease during this study. This may be because aspirin dosages were too low to provide any protective antiinflammatory effects in the brain. The use of acetaminophen (a pain relief medication with minimal antiinflammatory action) was also studied for comparison and did not result in lowered risk for Alzheimer's disease.

Are NSAIDs available for the treatment of Alzheimer's?
NSAIDs are currently available overthecounter for general use in pain relief. NSAIDs are not yet considered to be a preventative treatment for Alzheimer's disease. The results of Dr. Stewart's study are promising, but preliminary. Large-scale clinical trials using NSAIDs for the preventative treatment of Alzheimer's disease are necessary in order to determine effectiveness, appropriate dosage, and possible side effects. Clinical trials using NSAIDs have not yet been launched, but are expected to begin later this year.

Because it is known that extensive or prolonged use of NSAIDs can lead to gastrointestinal problems such as gastric irritation and bleeding, peptic ulcer disease, and impaired kidney function, the Alzheimer's Association does not recommend the use of NSAIDs as a preventative treatment for Alzheimer's. Prolonged use of any medication should be discussed with a physician.

Facts about Vitamin E, Selegiline and Alzheimer's Disease

What is Vitamin E?
Vitamin E is a vitamin that can be obtained naturally through the diet or by taking vitamin supplements. Previous research has shown that vitamin E can help prevent cardiovascular disease, increase immune response, and possibly help protect against some cancers, though all studies did not show these positive effects. Because vitamin E is an antioxidant, researchers believe that it may aid in the breakdown of free radicals that may be damaging brain cells in
individuals with Alzheimer's disease.

Natural sources of vitamin E include green, leafy vegetables, vegetable oils, nuts, seeds, seed oils, whole grains, wheat germ, rice, sweet potatoes and avocados. Vitamin E also is available in vitamin supplements, though little is known about the effects of high doses or possible interactions with other drugs. There are differences between the natural and synthetic forms of vitamin E. All medication decisions, including vitamin supplements and overthe-counter products, should be made only after consultation with a physician.

What is Selegiline?
Selegiline (also known as Deprenyl or Eldepryl) is a prescription drug currently used for the treatment of Parkinson's disease. Selegiline is also currently in clinical trials for the treatment of Alzheimer's disease. It can be associated with side effects including orthostatic hypertension, nausea, dizziness, confusion, vivid dreams and low blood pressure, particularly when taken in combination with other drugs, and therefore must be taken under a doctor's supervision.

What studies have been done using vitamin E and Selegiline to prevent or delay the onset of Alzheimer's?
In a recent study led by Mary Sano, Ph.D., of the Gertrude Sergievsky Center at Columbia University, College of Physicians and Surgeons, and colleagues at the nationwide Alzheimer's Disease Cooperative Study, individuals in the moderate stages of Alzheimer's disease, who for two years ingested either vitamin E or Selegiline, took a significantly longer time to reach more advanced stages of the disease than those who took a placebo. The research was funded by the National Institute on Aging and is reported in the April 24, 1997 issue of the New England Journal of Medicine. This study involved 341 individuals in the moderate stages of Alzheimer's who participated in a double blind, placebocontrolled, randomized, multicenter trial. Participants received Selegiline (10 milligrams per day), vitamin E (2,000 I.U. per day), both or a placebo for two years, and were followed to see when they reached one of the following endpoints: death, institutionalization, and inability to do certain basic activities of daily living or severe dementia.

Those participants who took vitamin E or Selegiline took significantly longer time to reach one of the primary outcomes than the placebo group, although thev did not demonstrate an improvement in symptoms. The researchers identified signs and symptoms that typically worsen over time. In patients taking these drugs, the symptoms or signs occurred later than those taking a placebo. There was no evidence of added benefit with combined treatment using both drugs. According to the researchers, it is not clear yet if the drugs were having an effect specifically on the disease process or on the overall health of the participants. Researchers report the drugs were well tolerated.

Is vitamin E available for the treatment of Alzheimer's?
At this time, we cannot recommend vitamin E specifically for the treatment of Alzheimer's disease, because there is no direct evidence that vitamin E prevents Alzheimer's disease. However, because previous research has demonstrated that vitamin E has other health benefits, there appears to be no reason not to take it in moderation.

In the study, 2000 I.U.s of vitamin E taken for two years delayed the clinical signs and symptoms of the disease for people with moderate stage Alzheimer's disease. The U.S. Government Recommended Dietary Allowance for vitamin E is 30 International Units (I.U.s) a day. Because vitamin E may be associated with increased bleeding in individuals with risk factors for these problems, all decisions regarding medications or vitamin supplements should be discussed with a physician.

Is Selegiline available for the treatment of Alzheimer's?
At this time, we cannot recommend Selegiline specifically for the treatment of Alzheimer's disease. Selegiline is currently only indicated for the treatment of Parkinson's disease and has not yet been approved by the Food and Drug Administration (FDA) for the treatment of Alzheimer's disease. The decision to take any drug must include weighing benefits and risks. If your doctor concludes that your condition was similar to that of the patients, in this study, and that the risks to you are not serious, he may choose to write a prescription for this medication.

This fact sheet is provided for your information only, and does not represent an endorsement of vitamin E or Selegiline by the Alzheimer's Association.

Hormone Replacement Therapy

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Facts About Ginkgo Biloba and Alzheimer's Disease

What is ginkgo biloba?
Ginkgo biloba is a plant extract containing several compounds that may have positive effects on cells within the brain and the body. Ginkgo biloba is thought to have both antioxidant and antiinflammatory properties, to protect cell membranes, and to regulate neurotransmitter function. Ginkgo has been used for centuries in traditional Chinese medicine, and currently is being used in Europe to alleviate cognitive symptoms associated with a number of neurological conditions.

Does ginkgo biloba prevent or delay the onset of Alzheimer's? In a recent study published in the Journal of the American Medical Association (October 22/29, 1997), Pierre L. Le Bars, M.D., Ph.D., of the New York Institute for Medical Research, and colleagues, found ginkgo biloba to have a positive effect in individuals with Alzheimer's disease.

This 52week study initially involved 309 patients suffering from mild to moderately severe dementia, caused by either Alzheimer's disease or multiinfarct dementia (also known as MID, or vascular dementia). These patients were divided into two groups; participants in one group were administered 120mg of ginkgo biloba extract each day, and participants in the second group received a placebo (sugar pill).

At the end of the study, data from only 202 of the participants was used to determine the efficacy of using ginkgo in the treatment of Alzheimer's disease, due to a significant drop out rate of participants during the course of the treatment. Participants were tested for improvement in cognition, improvement in daily living and social behavior, and positive changes in overall impairment. Researchers found that modest improvements took place in cognition, and in activities of daily living (such as eating and dressing) and social behavior, but no measurable difference was noticed in overall impairment.

Results from this study show that ginkgo may slightly help some individuals with Alzheimer's disease, but further research is needed in order to determine the exact mechanisms by which ginkgo works in the body. Also, results from this study are considered to be preliminary, because of the low number of participants involved and methodological issues associated with the research.

Is ginkgo biloba available for the treatment of Alzheimer's?
Ginkgo biloba is readily available in health food stores, and can be found in pill form, in tea bags, or in combination with other dietary supplements. However, research into the use of ginkgo biloba for the treatment of Alzheimer's disease is still preliminary. Further study of ginkgo biloba is necessary to fully understand its potential therapeutic value in treating individuals with Alzheimer's, and to uncover possible side effects associated with extensive or prolonged use. The Alzheimer's Association recommends that all decisions regarding medications or dietary supplements, such as ginkgo biloba, should be discussed with a physician to avoid complications, or harmful drug interactions.

What side effects are associated with the use of ginkgo biloba?
Few side effects are associated with the use of ginkgo as a dietary supplement, although it is known to reduce the ability of blood to clot, potentially leading to more serious conditions, such as hemorrhaging. This possibility of hemorrhaging may increase if ginkgo biloba is taken in combination with other anticoagulants, such as aspirin.

Where can I participate in a study of this or other drug treatments for Alzheimer's disease?
Currently, information about largescale clinical studies of ginkgo biloba for the treatment of Alzheimer's disease is not available.

This fact sheet is provided for your information only, and does not represent an endorsement of
ginkgo biloba by the Alzheimer's Association.

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