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John G. Csernansky, MD; Lei Wang, PhD; J. Philip Miller, AB; James E. Galvin, MD, MPH; John C. Morris, MD

Arch Neurol. 2005;62:1718-1722.

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.

Author Affiliations: Alzheimer’s Disease Research Center (Drs Csernansky, Wang, Galvin, and Morris and Mr Miller), the Departments of Psychiatry (Drs Csernansky and Wang), Neurology (Drs Galvin and Morris), Anatomy and Neurobiology (Dr Csernansky), and Pathology and Immunology (Dr Morris), and the Division of Biostatistics (Mr Miller), Washington University School of Medicine, St Louis, Mo.

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