Clinical:Alzheimer's Disease

Presently, there are five agents that are approved by the U.S. food and Drug Administration ( FDA) for the symptomatic treatment of AD. Four of the drugs work to enhance the cholinergic transmission in the brain by reducing the degradation of acetylcholine through inhibition of the enzyme acetylcholinesterase ( AchE). These medications are prescribed for mild to moderate AD and are are thought to delay or prevent symptoms from becoming worse for a limited time and may help control some behavioral symptoms. The medications include: Razadyne® (galantamine, formerly known as Reminyl® and now available as a generic drug), Exelon® (rivastigmine), and Aricept® (donepezil). Another drug, Cognex® (tacrine), was the first approved cholinesterase inhibitor but is rarely prescribed today due to safety concerns (liver toxicity).

Scientists do not yet fully understand how cholinesterase inhibitors work to treat AD, but research indicates that they prevent the breakdown of acetylcholine, a brain chemical believed to be important for memory and thinking. Rivastigmine inhibits both AchE and butyrylcholinesterase ( BuCh), in comparison to donepezil and galantamine which inhibit AchE but only have minimal inhibiton of BuChE. It is important to note that all of the AchE's except rivastigmine are eliminated via the liver.

No published study directly compares these drugs. Because they work in a similar way, switching from one of these drugs to another probably will not produce significantly different results. In fact clinically, one typically sees patients decline with the switching to another medication, not returning to their previous baseline. Therefore, switching to another medication is done cautiously and in persons who cannot tolerate a medication due to side effects.

Treatment for Moderate to Severe AD

A medication known as Namenda® (memantine), an N-methyl D-aspartate (NMDA) antagonist, is prescribed to treat moderate to severe AD. This drug’s main effect is to delay progression of some of the symptoms of moderate to severe AD. It may allow patients to maintain certain daily functions a little longer than they would without the medication. For example, Namenda® may help a patient in the later stages of AD maintain his or her ability to use the bathroom independently for several more months, a benefit for both patients and caregivers.

Namenda® is believed to work by regulating glutamate, an important brain chemical. When produced in excessive amounts, glutamate may lead to brain cell death. Because NMDA antagonists work very differently from cholinesterase inhibitors, the two types of drugs can be prescribed in combination.

The FDA has also approved Aricept® for the treatment of moderate to severe AD.

Dosage and Side Effects

Doctors usually start patients at low drug doses and gradually increase the dosage based on how well a patient tolerates the drug. It is advised to do a titration schedule "up" over a four week period. There is some evidence that certain patients may benefit from higher doses of the cholinesterase inhibitors, however many clinicians do not go "off label", due to the higher risk of side effects. The recommended effective dosages of drugs prescribed to treat the symptoms of AD and the drugs’ possible side effects are summarized in the table (see below).

Patients should be monitored when a drug is started. Report any unusual symptoms to the prescribing doctor right away. It is important to follow the doctor’s instructions when taking any medication, including vitamins and herbal supplements. Also, let the doctor know before adding or changing any medications.

Testing New AD Drugs

Clinical trials are the best way to find out if promising new treatments are safe and effective in humans. Volunteer participants are needed for many AD trials conducted around the United States. To learn more, talk with your doctor or visit the ADEAR Center’s listing of clinical trials at [www.nia.nih.gov/Alzheimers/ResearchInformation/ClinicalTrials]. More information is available at [www.ClinicalTrials.gov].

For More Information

To learn about support groups, research centers, research studies, and publications about AD, contact the following resources:

Alzheimer’s Disease Education and Referral (ADEAR) Center

P.O. Box 8250 Silver Spring, MD 20907-8250 800-438-4380 (toll-free) [www.nia.nih.gov/Alzheimers]

A service of the National Institute on Aging (NIA), the ADEAR Center offers information and publications for families, caregivers, and professionals on diagnosis, treatment, patient care, caregiver needs, long-term care, education and training, and research related to AD. Staff members answer telephone, email, and written requests and make referrals to local and national resources. The ADEAR website offers free, online publications in English and Spanish; email alert and online Connections newsletter subscriptions; an AD clinical trials database; the AD Library database; and more.

Alzheimer’s Association

225 North Michigan Avenue, Floor 17 Chicago, IL 60601-7633 800-272-3900 (toll-free) 866-403-3073 (TDD/toll-free) [www.alz.org]

The Alzheimer’s Association is a national nonprofit association with a network of local chapters that provide education and support for people diagnosed with AD, their families, and caregivers. The Association also supports research on AD.

Table - Medications to Treat Alzheimer's Disease

Note: This brief summary does not include all information important for patient use and should not be used as a substitute for professional medical advice. Consult the prescribing doctor and read the package insert before using these or any other medications or supplements.