Neuroanatomical predictors of response to donepezil therapy in patients with dementia.

BACKGROUND Patients with dementia of the Alzheimer type (DAT) respond variably to treatment with acetylcholinesterase inhibitors. OBJECTIVE To determine whether measures of hippocampal volume and shape predict the response to donepezil in patients with DAT. DESIGN T1-weighted, magnetic resonance images were obtained from patients with DAT, who subsequently underwent treatment with donepezil. Brain-mapping algorithms were used to quantify hippocampal volume and shape, and growth curves were used to estimate clinical outcome. SETTING A referral outpatient center specializing in treatment of dementia. PATIENTS Thirty-seven patients with very mild or mild DAT received donepezil therapy for up to 4 weeks before magnetic resonance imaging and for 24 to 96 weeks after magnetic resonance imaging. INTERVENTION Donepezil, 10 mg/d. MAIN OUTCOME MEASURE Rate of change in the cognitive portion of the Alzheimer's Disease Assessment Scale total scores. RESULTS Smaller hippocampal volume and inward variation of the lateral and inferomedial portions of the hippocampal surface were correlated with a poorer response to donepezil therapy. CONCLUSIONS Measures of hippocampal volume and surface variation can be used to predict the response of patients with DAT to the acetylcholinesterase inhibitor donepezil.