Prediction of response to donepezil in Alzheimer's disease: combined MRI analysis of the substantia innominata and SPECT measurement of cerebral perfusion

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We performed combined studies of magnetic resonance imaging (MRI) analysis of the substantia innominata and single photon emission CT (SPECT) measurement of cerebral perfusion with the goal of predicting which patients with Alzheimer's disease are most likely to respond to donepezil treatment.


Ninety-one patients treated with donepezil were divided into responders and non-responders on the basis of changes in their MMSE scores from baseline to study endpoint. The thickness of the substantia innominata was measured on the coronal T2-weighted MRI through the anterior commissure. SPECT data were analysed using three-dimensional stereotactic surface projections.


Responders had significantly greater atrophy of the substantia innominata, but less prominent frontal hypoperfusion than non-responders. Receiver operating characteristic analysis revealed that combined MRI and SPECT examination showed an overall discrimination rate of 70% between responders and non-responders.


Our results suggest that responder patients have more severe damage in the cholinergic system and/or less prominent frontal cortical dysfunction. Combined MRI analysis of the substantia innominata and SPECT measurement of frontal perfusion at baseline may help to predict response to donepezil treatment in patients with Alzheimer's disease.

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