Shen Guoping, Xu Xue, Li Minping, Sun Zaiyuan, Wei Linyu, Deng Zhezhi, Lin Zehuang, Huang Jianwen, Qi Weiwei, Xu Jia
Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, PR China.
Department of Neurology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, PR China.
CNS Neurosci Ther. 2025 Jun;31(6):e70492. doi: 10.1111/cns.70492.
Not only drug and non-drug development but also non-therapeutic research in Alzheimer's disease (AD) clinical trials is unclear.
The participants were AD clinical trials obtained from the clinicaltrials.gov registry. The research objectives and interventions of those trials were analyzed. Bibliometric network analysis of those published articles in PubMed was also conducted.
A total of 1681 clinical trials and 565 corresponding published articles in the past 20 years were included in the analysis. "Safety", "dose", "adverse events", and "biomarker" were the most frequently used words that appeared in the title or abstract of published articles. The top three classes of 362 drugs were anti-Amyloid, enhancing acetylcholine, neurotransmitter, or targeting its receptor. The physical therapy, diet, and cognitive training ranked as the first three classes of non-drug therapy. Imaging, risk factors, and molecular biomarkers were the three most abundant categories in non-therapeutic research, and three fields of prevention, risk factors, and the dental or intestinal microbiome showed an escalated trend (All P < 0.05).
The results described a comprehensive landscape for the clinical studies of AD. Although most drugs treated AD abortively, the success of lecanemab and decanemab provides confidence for us to further study the pathogenesis of AD and explore new therapeutic targets to develop anti-AD drugs. Rising non-drug and non-therapeutic research will provide more possible methods for the treatment and prevention of AD in thefuture.
在阿尔茨海默病（AD）临床试验中，不仅药物和非药物研发情况不明，非治疗性研究亦是如此。
研究对象为从clinicaltrials.gov注册库获取的AD临床试验。对这些试验的研究目标和干预措施进行了分析。还对PubMed上发表的相关文章进行了文献计量网络分析。
分析纳入了过去20年中的1681项临床试验及565篇相应的发表文章。“安全性”“剂量”“不良事件”和“生物标志物”是发表文章标题或摘要中最常出现的词汇。362种药物的前三类分别是抗淀粉样蛋白、增强乙酰胆碱、神经递质或靶向其受体的药物。物理治疗、饮食和认知训练是非药物治疗的前三类。影像学、危险因素和分子生物标志物是非治疗性研究中最丰富的三个类别，预防、危险因素以及牙齿或肠道微生物组这三个领域呈上升趋势（所有P<0.05）。
研究结果描绘了AD临床研究的全面图景。尽管大多数治疗AD的药物未获成功，但lecanemab和decanemab的成功为我们进一步研究AD的发病机制和探索新的治疗靶点以开发抗AD药物提供了信心。不断兴起的非药物和非治疗性研究将为未来AD的治疗和预防提供更多可能的方法。
