Alzheimer's disease is the most common cause of dementia affecting older people, and is associated with loss of cholinergic neurons in parts of the brain. Acetylcholinesterase inhibitors, such as donepezil, delay the breakdown of acetylcholine released into synaptic clefts and so enhance cholinergic neurotransmission.
Donepezil is beneficial for people with mild, moderate and severe dementia due to Alzheimer's disease, in being associated with improvements in cognitive function and activities of daily living. Adverse effects were consistent with the cholinergic actions of the drug and were the most likely cause of withdrawal from treatment in the first 12 weeks. Effects on cognition remained measurable and statistically significant at 52 weeks of treatment in one study.
There is some evidence that use of donepezil is neither more nor less expensive compared with placebo when assessing total health care resource costs. Benefits on the 10 mg/day dose were marginally larger than on the 5 mg/day dose. Taking into consideration the better tolerability of the 5 mg/day donepezil compared with the 10 mg/day dose, together with the lower cost, the lower dose may be the better option. The debate on whether donepezil is effective continues despite the evidence of efficacy from the clinical studies because the treatment effects are small and are not always apparent in practice, and because of the cost of the drug.