To the Editor: Many individuals with Down’s syndrome who are over 40 years of age develop clinical and neuropathological evidence of Alzheimer’s disease. Cholinergic deficits have been linked to neuronal loss in the nucleus basalis of Meynert in patients with Alzheimer’s disease, and the nucleus basalis of Meynert in patients with Down’s syndrome contains fewer neurons than are found in normal comparison subjects +(1). This implies that cholinergic deficits are also present in the nucleus basalis of Meynert in patients with Alzheimer’s disease associated with Down’s syndrome. Plasma concentrations of donepezil are related to the percentage of red blood cell acetylcholinesterase inhibition and to improvements in cognitive functioning +(2). Patients with Down’s syndrome were excluded from donepezil clinical trials +(2), and therefore much fewer data regarding its pharmacological effects are available for this population. We report on three patients with Alzheimer’s disease associated with Down’s syndrome who were treated with donepezil.

Patients with Down’s syndrome may respond to medications used to treat Alzheimer’s-associated psychopathology +(3). However, further studies are required to adequately assess the safety and efficacy of donepezil for Alzheimer’s disease associated with Down’s syndrome. In these cases, donep­ezil treatment resulted in adverse effects related primarily to peripheral cholinergic overstimulation, with symptoms of urinary incontinence in two of three patients. Administration of a peripherally acting cholinergic antagonist or possible use of a lower dose of donepezil may block these side effects, ­allowing for safe use of this medication in this population. Clinicians should be alert to the possibility of adverse effects when administering donepezil to individuals with Down’s syndrome.