In data from the U.S. phase II and III pivotal Alzheimer’s disease clinical trials, which ranged from 3 to 6 months’ duration (donepezil-treated group: N=747, placebo-treated group: N=355), 3% of the individuals in the placebo group reported urinary incontinence, compared to 1% of the donepezil group. Agitation was reported in 7% of the patients taking placebo compared to 4% of those taking donepezil. The dose of donepezil in the phase II trial ranged from 1 to 5 mg/day, whereas in the phase III trial, it was either 5 or 10 mg/day after 1 week at a dose of 5 mg/day (data available from Eisai, Inc.). In general, cholinergic side effects can be minimized by increasing the dose from 5 to 10 mg/day more slowly (e.g., after 6 weeks, rather than 1 week) (from donepezil package insert), by instituting temporary drug holidays, and/or by decreasing the dose from 10 to 5 mg/day if side effects occur at the higher dose (3). However, readers must bear in mind that donepezil has not been systematically investigated for use in patients with Down’s syndrome. Randomized controlled clinical trials of cholinergic therapy are warranted in adult and pediatric patients with Down’s syndrome; both are currently underway at our center.