Fornalik Michał, Moska Sandra, Gimła Mariola, Yabluchanskiy Andriy, Bonin Pinto Camila
Aging and Metabolism Research Program, The Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Faculty of Medicine, Poznan University of Medical Sciences, Poznan, Poland.
Clin Exp Med. 2025 Jun 10;25(1):196. doi: 10.1007/s10238-025-01708-w.
Cancer-related cognitive impairment (CRCI) affects a significant proportion of cancer patients and survivors, impacting their memory, focus, mood, and quality of life. While non-pharmacological interventions have shown effectiveness in managing this condition, some studies have also explored various pharmacological agents, including donepezil, a reversible acetylcholinesterase inhibitor. This compound demonstrated beneficial effects on cognition in Alzheimer's disease; however, its effectiveness in CRCI remains unknown. This systematic review and meta-analysis aims to evaluate the efficacy of donepezil in improving cognitive outcomes in cancer patients. We conducted a search of PubMed/Medline, Embase, Cochrane Library, ClinicalTrials.gov, and the International Clinical Trials Registry Platform. Both randomized controlled trials and observational studies were included. We extracted data on cognitive outcomes of donepezil treatment, including the Hopkins Verbal Learning Test-Revised (HVLT-R), Trail Making Test (TMT), and Controlled Oral Word Association Test (COWA), as well as reported adverse events (AEs). Out of 896 identified records, nine studies involving 837 patients met the inclusion criteria, including five RCTs and four observational studies. Donepezil failed to demonstrate significant improvements in cognitive outcomes in HVLT-R, TMT, and COWA. Fatigue, measured as a secondary outcome, also showed no significant improvement. AEs, such as insomnia and headache, were more prevalent in adults than children. Donepezil did not increase the risk of AEs compared to placebo. This meta-analysis found that donepezil does not provide cognitive improvements for CRCI patients. Given the complex and multifactorial nature of CRCI, the lack of efficacy suggests that donepezil may not address the underlying mechanisms of the condition.
癌症相关认知障碍（CRCI）影响着相当一部分癌症患者及其幸存者，对他们的记忆力、注意力、情绪和生活质量产生影响。虽然非药物干预已显示出对这种情况的管理效果，但一些研究也探索了各种药物制剂，包括多奈哌齐，一种可逆性乙酰胆碱酯酶抑制剂。该化合物在阿尔茨海默病中对认知功能显示出有益作用；然而，其在CRCI中的有效性仍不明确。本系统评价和荟萃分析旨在评估多奈哌齐在改善癌症患者认知结局方面的疗效。我们检索了PubMed/Medline、Embase、Cochrane图书馆、ClinicalTrials.gov和国际临床试验注册平台。纳入了随机对照试验和观察性研究。我们提取了多奈哌齐治疗的认知结局数据，包括修订版霍普金斯言语学习测验（HVLT-R）、连线测验（TMT）和受控口语词语联想测验（COWA），以及报告的不良事件（AE）。在896条识别记录中，9项涉及837名患者的研究符合纳入标准，包括5项随机对照试验和4项观察性研究。多奈哌齐在HVLT-R、TMT和COWA的认知结局方面未显示出显著改善。作为次要结局测量的疲劳也未显示出显著改善。失眠和头痛等不良事件在成人中比儿童中更普遍。与安慰剂相比，多奈哌齐未增加不良事件的风险。这项荟萃分析发现，多奈哌齐不能改善CRCI患者的认知功能。鉴于CRCI的复杂性和多因素性质，缺乏疗效表明多奈哌齐可能无法解决该病症的潜在机制。
