Donepezil for dementia due to Alzheimer's disease Audio summaries | Evidence Aid summaries | Cochrane Methodology abstracts 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.The results show some improvement in global clinical state (assessed by a clinician) in people treated with 5 and 10 mg/day of donepezil compared with placebo at 24 weeks for the number of patients showing improvement (OR 2.38, 95% CI 1.78 to 3.19, P = 0.00001, OR 1.82, 95% CI 1.42 to 2.35, P 0.00001). Benefits of treatment were also seen on measures of activities of daily living and behaviour, but not on the quality of life score. There were significantly more withdrawals before the end of treatment from the 10 mg/day (289/1125 24% 10 mg/day vs 219/1079 20% placebo, OR 1.35, 95% CI 1.11 to 1.65, P = 0.003) but not the 5 mg/day, (100/561 18% 5 mg/day vs 109/568 19% placebo, OR 0.91, 95% CI 0.68 to 1.24, P = 0.56) donepezil group compared with placebo which may have resulted in some overestimation of beneficial changes at 10 mg/day. Benefits on the 10 mg/day dose were marginally larger than on the 5 mg/day dose. The results were similar for all severities of disease.
