Drugs For Memory And Cognitive Function - The Search For Therapies: Alzheimers

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Drugs for memory and cognitive function

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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). All these prescription medications work by affecting particular chemicals in the brain and offer modest improvements in memory and cognitive function in some people with Alzheimer's (see Table 3).

Table 3: 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.

Donepezil, rivastigmine, galantamine, and tacrine belong to a class of drugs called acetylcholine esterase inhibitors. They work to raise the levels of acetylcholine in the brain, because a deficiency in this neurotransmitter is believed to account for the memory problems of Alzheimer's disease. They seem to work by blocking an enzyme that destroys acetylcholine, which presumably makes more acetylcholine available for transmitting impulses from one brain cell to another. The drugs are effective for people with mild to moderate Alzheimer's disease. Tacrine is rarely used because it's been associated with severe liver problems.

Only about 30%–50% of the people who take this class of drugs show benefits. These medications may temporarily stabilize or improve memory problems and other cognitive symptoms. For example, one 2001 study found that taking donepezil for at least 9 months postponed a patient's need to move to a nursing home by about 21 months.

Memantine has a different mode of action. It is an NMDA (N-methyl-D-aspartate) antagonist — it works by blocking glutamate, another neurotransmitter, from attaching to NMDA receptors in the brain. This is beneficial because glutamate is an excitotoxin, a neurotransmitter that usually activates neurons but in excessive amounts can destroy them. Research suggests that excitotoxins may cause some of the neuron degeneration that occurs with Alzheimer's disease (see "Antioxidants").

Memantine is used to treat symptoms of moderate to severe Alzheimer's disease. Several studies show that people in this stage of Alzheimer's who took memantine had better scores on tests of cognitive functions and daily functioning than did similar people who took a placebo. Studies are under way to see if memantine can also help people with mild to moderate symptoms.

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Last updated:	January 23, 2007

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