title: PET Evidence of the Effect of Donepezil on Cognitive Performance in an Animal Model of Chemobrain.
abstract: A considerable number of patients with breast cancer complain of cognitive impairment after chemotherapy. In this study, we showed that donepezil enhanced memory function and increased brain glucose metabolism in a rat model of cognitive impairment after chemotherapy using behavioral analysis and positron emission tomography (PET). We found that chemotherapy affected spatial learning ability, reference memory, and working memory and that donepezil improved these cognitive impairments. According to PET analysis, chemotherapy reduced glucose metabolism in the medial prefrontal cortex and hippocampus, and donepezil increased glucose metabolism in the bilateral frontal lobe, parietal lobe, and hippocampus. Reduced glucose metabolism was more prominent after treatment with doxorubicin than cyclophosphamide. Our results demonstrated the neural mechanisms for cognitive impairment after chemotherapy and show that cognition was improved after donepezil intervention using both behavioral and imaging methods. Our results suggested that donepezil can be employed clinically for the treatment of cognitive deficits after chemotherapy.
authors.affiliation: Division of RI-Convergence Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea; Department of Nuclear Medicine, Korea Cancer Center Hospital, Seoul 01812, Republic of Korea.
authors.forename: Ilhan
authors.initials: I
authors.lastname: Lim
authors.affiliation: Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Hye-Young
authors.identifier: 0000-0002-1947-3989
authors.initials: HY
authors.lastname: Joung
authors.affiliation: Division of RI-Convergence Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea.
authors.forename: A Ram
authors.initials: AR
authors.lastname: Yu
authors.affiliation: Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Insop
authors.identifier: 0000-0002-8014-9782
authors.initials: I
authors.lastname: Shim
authors.affiliation: Division of RI-Convergence Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea.
authors.forename: Jin Su
authors.identifier: 0000-0001-8965-9538
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D004195:Disease Models, Animal; D000077265:Donepezil; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D007189:Indans / Q000494:pharmacology* / Q000627:therapeutic use*; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use*; D049268:Positron-Emission Tomography; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents; D007189:Indans; D010880:Piperidines; D019788:Fluorodeoxyglucose F18; D000077265:Donepezil