Efficiency of Donepezil in Elderly Patients Undergoing Orthopaedic Surgery Due To Underlying Post-Operative cognitive Dysfunction: Study Protocol for A Multicentre Randomised Controlled Trial

Abstract Background Post-operative cognitive dysfunction (POCD) is an overarching term used to describe cognitive impairment identified in the preoperative or post-operative period. After surgical operations, older patients are particularly vulnerable to memory disturbances and other types of cognitive impairment. However, the pathogenesis of POCD remains unclear and no confirmed preventable or treatment strategy avilable. Our previous study demonstrated that the concentration of choline acetyl transferase in the cerebral spinal fliud was a predictive factor of POCD, and donepezil is an acetylcholinesterase inhibitor which was used in clinical for the treatment of alzheimer's disease can prevent the learning and memory impairment after anesthesia/surgery in aged mice. This study aimed to determine the critical role of donepezil in preventing cognitive impairment in elder patients undergoing orthopaedic surgery. Methods A multicentre, double-blind, placebo-controlled, crossover clinical trial will be performed to assess the efficacy of donepezil in elderly patients undergoing orthopaedic surgery. Participants (n = 360) will receive donepezil (5 mg once daily) or placebo from 1 day prior to surgery until 5 days after surgery. Neuropsychological tests will be measured at 1 day before the operation and 1 week, 1 month, 6 months and 1 year after the operation. Discussion This research project mainly aimed to study the effects of donepezil in elderly patients undergoing orthopaedic surgery due to underlying POCD and to investigate the underlying physiological and neurobiological mechanisms of these effects. The results may provide important implications for the development of effective interfering strategies, specifically regarding cognitive dysfunction therapy using drugs. Trial registration: ClinicalTrials.gov, NCT04423276. Registered on 14 June 2020.