Donepezil reduces cognitive impairment associated with anti-cancer drugs in a mouse model

Adjuvant cancer chemotherapy often causes cognitive impairment that can be long-lasting and adversely affect quality of life. The present study sought to determine if the cognitive enhancing drug, donepezil, can reduce cognitive impairment induced by a combination of methotrexate +5-fluorouracil, two drugs commonly used in cancer chemotherapy. Four groups of mice: (1) chemotherapy-only; (2) chemotherapy+donepezil; (3) saline-only; (4) saline+donepezil, were administered the following learning and memory tests: (1) standard spatial memory (SM); (2) non-spatial cued memory (CM); (3) non-matching-to-sample (NMTS) rule-learning; (4) delayed-NMTS (DNMTS). The chemotherapy-only group was impaired on the SM, NMTS, and DNMTS tasks. Chemotherapy-induced cognitive deficits were significantly reduced in the chemotherapy+donepezil group whose performance on some measures was very similar to that of the saline-only group. There was no evidence that donepezil improved the performance of saline-treated mice. The results confirm the adverse effects of chemotherapy on cognitive function and demonstrate that they can be ameliorated by donepezil, which is widely used to treat cognitive impairment in other clinical populations (e.g., Alzheimer's disease).