Currently, there is no definitive proof that use of donepezil or other similar agents alters the course or progression of Alzheimer's disease. However, 6-12 month controlled studies have shown modest benefits in cognition and/or behavior.^[3] Pilot studies have reported that donepezil therapy may potentially have effects on markers of disease progression, such as hippocampal volume. Therefore, many neurologists, psychiatrists, and primary care physicians use donepezil in patients with Alzheimer's disease. In 2005, the UK National Institute for Clinical Excellence (NICE) withdrew its recommendation for use of the drug for mild-to-moderate AD, on the basis that there is no significant improvement in functional outcome, of quality of life, or of behavioral symptoms. However, NICE revised its guidelines to suggest that donepezil be used in moderate stage patients for whom the evidence is strongest. It is currently not licensed for use in the treatment of Alzheimer's disease in the UK at any other stage.^[4]

While the drug is currently indicated for mild to moderate Alzheimer's, there is also evidence from 2 clinical trials that indicates it may be effective for moderate to severe disease. An example of this is a Karolinska Institute paper published in The Lancet in early 2006, which states that donepezil improves cognitive function even in patients with severe Alzheimer's disease symptoms.^[5]