Alzheimer's disease is the most common cause of dementia, affecting 4.5 million individuals in the United States. It is a slowly progressive disease that begins insidiously. Patients have cognitive symptoms such as difficulty learning new information, and may also have changes in behavior, mood, and personality.

Drug therapy is one part in the management of Alzheimer's disease. Commonly used drugs that slow the progression of symptoms include cholinesterase inhibitors such as donepezil, and drugs which block the N-methyl-D-aspartate receptor, such as memantine.

The "Drug Class Review on Alzheimer's Drugs" compares the safety and effectiveness of five drugs. A summary of the findings is below.

How do Alzheimer's drugs compare for treating symptoms?

There is fair evidence that the following drugs have modest effects on stabilizing symptoms, treating behavioral problems, and improving function in patients with Alzheimer's disease: donepezil, galantamine, rivastigmine, tacrine, and memantine. The numbers of patients needed to be treated for one patient to have either a global response or an improvement in cognitive function are 12 and 10 respectively.

Limited evidence exists on how other drugs compare, there are mixed results for donepezil vs. galantamine. Limited evidence for donepezil vs. rivastigmine suggests only minimal differences. [full review]

How do Alzheimer's drugs compare in their time to have an effect?

There is insufficient evidence to determine whether the drugs used to treat Alzheimer's disease differ in the time they take to have an effect - most trials only reported long-term outcomes. [full review]

How do Alzheimer's drugs compare in safety?

When donepezil was compared with galantamine and rivastigmine in patients with Alzheimer's disease, there were no differences in cardiovascular events and overall adverse events. Indirect evidence indicates a higher risk of liver damage for tacrine, whereas donepezil, galantamine, rivastigmine, and memantine were not associated with hepatotoxicity.

Tolerability may vary among these drugs, for example, gastrointestinal-related events were more common with rivastigmine. [full review]

Does age, gender, or the presence of vascular dementia influence the safety or effectiveness Alzheimer's drugs?

Overall the level of evidence is poor. Indirect comparisons suggest that age, gender, or ethnicity does not influence the safety and efficacy of donepezil. Limited evidence suggests that patients older than 75 years may derive greater benefit from rivastigmine.

In patients who have Alzheimer's disease and vascular dementia, the following drugs have been shown to provide benefit: donepezil, galantamine, rivastigmine, and memantine. [full review]

Drugs included in this review

Further information

This PubMed Clinical Q&A was reviewed by Richard A. Hansen, PhD.

For the full report and evidence tables, please see:
Hansen RA, Gartlehner G, Kaufer DJ, et al. Drug Class Review: Alzheimer's Drugs: Final Report [Internet]. Portland (OR): Oregon Health & Science University; 2006 Jun. Available at: http://www.ncbi.nlm.nih.gov/books/NBK10310/.