Donepezil (Aricept) for Alzheimer's Disease
Also known as: Aricept, E2020
The most widely prescribed cholinesterase inhibitor for Alzheimer's, providing symptomatic cognitive benefit without disease modification.
Mechanism of Action
Donepezil reversibly inhibits acetylcholinesterase (AChE), increasing synaptic acetylcholine concentration in the brain. The cholinergic hypothesis posits that Alzheimer's cognitive decline partially results from loss of cholinergic neurons in the nucleus basalis of Meynert. By preserving acetylcholine, donepezil temporarily improves cognitive and functional performance.
General mechanism: Reversible acetylcholinesterase inhibitor. Increases synaptic acetylcholine for cognitive symptom management.
Current Evidence
Extensive clinical evidence shows modest but consistent cognitive benefit (1-3 points on ADAS-cog) lasting 6-12 months. Does not slow disease progression. Combination with memantine provides additive benefit. Over 25 years of real-world safety data.
Clinical Status: FDA-approved (1996). Generic available. First-line symptomatic treatment worldwide. Often combined with memantine in moderate-severe AD.
Safety Profile
GI effects (nausea, diarrhea, vomiting) are common, especially during dose titration. Bradycardia risk in susceptible patients. Well-established long-term safety.
Key Research Questions
- Does earlier initiation of donepezil provide longer-lasting symptomatic benefit?
- What is the optimal combination strategy with disease-modifying therapies like lecanemab?
- Can cholinergic biomarkers predict individual response magnitude?