Medications
Most drugs currently being used or that are under investigation to treat Alzheimer's are aimed at slowing progression. To date, none are cures. In fact, the improvements from some of these drugs may be so modest that even the patients and their families are not aware of them. Even in these cases, however, the drugs may delay the need for admission to nursing homes.
There are currently two drug classes that have been approved by the U.S. Food and Drug Administration (FDA) to treat the cognitive symptoms of Alzheimer's disease:
- Cholinesterase inhibitors (generally used to treat mild-to-moderate Alzheimer's)
- N-methyl-D-aspartate (NMDA) receptor antagonists (used to treat moderate-to-severe Alzheimer's)
Cholinesterase Inhibitors
Cholinesterase inhibitors are designed to protect the cholinergic system, which is essential for memory and learning and is progressively destroyed in Alzheimer's. These drugs work by preventing the breakdown of the brain chemical acetylcholine and are recommended for the treatment of mild-to-moderate Alzheimer's. The first cholinesterase inhibitor, tacrine, was approved in 1993 but is rarely prescribed today due to safety concerns. The three most commonly prescribed cholinesterase inhibitors are donepezil (approved in 1996), rivastigmine (approved in 2000), and galantamine (approved in 2001).
Cholinesterase inhibitors may increase the risk for gastrointestinal bleeding or ulcers, and patients should be cautious about concurrent use of NSAIDs (which can also cause gastric irritation). Common side effects of cholinesterase inhibitors, especially when taken at higher doses, may include nausea, vomiting, diarrhea, and upset stomach.
- Donepezil. Donepezil (Aricept) is taken once a day and has only modest benefits but it does help slow loss of function and reduce caregiver burden. It works equally in patients with or without the ApoE4 gene. In a 2004 study, donepezil appeared to help improve memory and daily living ability in patients with moderate-to-severe Alzheimer's when taken in combination with memantine. Several trials, including an important 2005 New England Journal of Medicine (NEJM) study, have found that donepezil may have short-term benefits for patients with mild cognitive impairment by delaying progression to AD. In the NEJM study, donepezil slowed progression during the first year of therapy, but demonstrated no benefits by the conclusion of the 3-year trial.
- Rivastigmine. Rivastigmine (Exelon) targets two enzymes (the major one, acetylcholinesterase, and butyrylcholinesterase). It is taken twice a day. This drug may be particularly beneficial for patients with rapidly progressing disease. It has slowed or slightly improved disease status even in patients with advanced disease. Rivastigmine may cause significantly more side effects than donepezil, including nausea, vomiting, and headache.
- Galantamine (Razadyne). Galantamine not only protects the cholinergic system but also acts on nicotine receptors, which are also depleted during Alzheimer's. Studies report that it improves daily living, behavior, and mental functioning, including in patients with mild to advanced-moderate Alzheimer's disease and those with a mix of Alzheimer's disease and vascular dementia. Some studies have suggested that the effects of galantamine may persist for a year or longer and even strengthen over time. In 2005, the name of galantamine was changed from Reminyl to Razadyne.
- Tacrine. Tacrine (Cognex) was the first cholinergic protective drug. It needs to be taken four times a day, has only modest benefits, and has no benefits for patients who carry the ApoE4 gene. In high doses, it can also injure the liver. In general, newer cholinergic protective drugs that do not pose as great a risk for the liver are now used for Alzheimer's.
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