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Effect of donepezil on brain acetylcholinesterase activity in patients with AD measured by PET

From the Division of Advanced Technology for Medical Imaging (Drs. Shinotoh, Fukushi, Nagatsuka, Aotsuka, Tanaka, Ota, Tanada, and Irie), National Institute of Radiological Sciences, Chiba; Asahi Neurological Hospital (Dr. Shinotoh), Chiba; Department of Neurology (Dr. Aotsuka), Chiba University School of Medicine, Chiba; ADME/TOX Research Institute (Dr. Nagatsuka), Daiichi Pure Chemicals Co. Ltd., Ibaraki; Department of Neurosurgery (Dr. Tanaka), Tokyo Women’s College, Tokyo; and Department of Psychiatry (Dr. Ota), Juntendo University, Tokyo, Japan.

Address correspondence and reprint requests to Dr. Toshiaki Irie, Division of Advanced Technology for Medical Imaging, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba-shi, Chiba, Japan; e-mail: t_irie{at}nirs.go.jp

Acetylcholinesterase (AChE) activities in the brain of three patients with AD were measured once before and once during donepezil treatment (5 mg/d in two patients, 3 mg/d in one patient) using PET and N-[¹¹C]methylpiperidin-4-yl acetate. Donepezil reduced k₃ values, an index of AChE activity, in the cerebral cortex by 39 ± 5%. All patients showed some degree of symptomatic improvement, and it was concluded that this improvement was likely caused by improved cholinergic activity by inhibition of AChE in the brain.

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