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Cortical Activation During Cholinesterase-Inhibitor Treatment in Alzheimer Disease

Preliminary Findings From a Pharmaco-fMRI Study

Received March 21, 2004; revised August 13, September 3, 2004; accepted September 21, 2004. From the Dept. of Psychiatry, Univ. of Tübingen, Tübingen, Germany (TTJK, DTL), the Section of Experimental MRI of the CNS, Dept. of Neuroradiology, Univ. of Tübingen, Tübingen, Germany (ME, WG), and the Dept. of Psychiatry and Psychotherapy, Univ. of Aachen, Aachen, Germany (TTJK). Send correspondence and reprint requests to T. Kircher, M.D., Ph.D., Dept. of Psychiatry, RWTH Aachen University, Pauwelsstr. 30, D-52072 Aachen, Germany. e-mail: tkircher{at}ukaachen.de
© 2005 American Association for Geriatric Psychiatry

Objective: Cholinesterase inhibitors improve cognitive functioning in Alzheimer disease (AD). The authors studied, with functional magnetic resonance imaging (fMRI), the neural mechanism by which this cholinergic enhancement improves memory encoding in AD over longer time periods. Methods: Brain activation was measured in 10 patients with AD and 10 healthy elderly comparison subjects with fMRI while they were encoding novel faces. Patients were scanned again after a 10-week open treatment with the cholinesterase-inhibitor donepezil. Results: Neuropsychologically-tested memory performance improved during the treatment phase in the patients. During the encoding of novel faces, elderly comparison subjects showed more activation in the right fusiform gyrus than the group of AD patients. After a 10-week treatment with donepezil, the fusiform gyrus was also activated in patients, similar to the comparison group. Conclusions: The right fusiform gyrus is associated with the processing of faces. Cholinergic enhancement augments selective attention by increased selectivity of perceptual responses in patients with AD. This mechanism may contribute to a more efficient processing of the attended stimulus and thus be a mechanism underlying clinical improvement of cognitive functioning. These promising preliminary findings need to be confirmed in a larger, controlled trial in which both fMRI and attention measures serve as outcomes.

Key Words: Alzheimer Disease • fMRI • Cholinesterase Inhibitors. Donepezil

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