The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, China.
The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
Medicine (Baltimore). 2024 Apr 19;103(16):e37799. doi: 10.1097/MD.0000000000037799.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Dementia severity was assessed mainly through cognitive function, psychobehavioral symptoms, and daily living ability. Currently, there are not many drugs that can be selected to treat mild to moderate AD, and the value of drugs remains controversial.
The aim of this study is to quantitatively evaluate the efficacy and safety of cholinesterase inhibitors (ChEIs), memantine, and sodium oligomannate (GV-971) in the treatment of patients with AD. Additionally, molecular docking analysis will be used to investigate the binding affinities of donepezil, galantamine, rivastigmine, and memantine with key receptor proteins associated with AD, including beta-amyloid (Abeta), microtubule-associated protein (MAP), apolipoprotein E4 (APOE4), and Mitofusin-2 (MFN2), to further validate the results of the meta-analysis.
We obtained clinical trials characterized by randomization, placebo control, and double-blinded methodologies concerning ChEIs, memantine, and GV-971. Statistical analysis was performed using Review Manager Version 5.4 software. Molecular docking was also conducted to evaluate the results.
All drugs improved the cognitive function, with the effect value ranging from -1.23 (95% CI -2.17 to -0.30) for 20 mg memantine to -3.29 (95% CI -4.14 to -2.45) for 32 mg galantamine. Although 32 mg galanthamine and GV-971 did not improve the clinicians' Global Impression of Change scale, other drugs showed significant results compared with placebo. On NPI, only 10 mg of donepezil and 24 mg of galantamine had improvement effects. On ADCS/ADL, only 20 mg memantine and 900 mg GV-971 had no significant difference from the placebo. Donepezil 5 mg and GV-971 900 mg did not increase the drug withdrawal rates due to various reasons or adverse reactions when compared to the placebo. Donepezil demonstrated superior binding to the protein and exhibited greater efficacy compared to other drugs.
ChEIs, memantine, and GV-971 all can slow the progression of AD but have different effects on respective assessments. Donepezil and GV-971 were relatively well tolerated.
阿尔茨海默病（AD）是一种进行性神经退行性疾病。痴呆严重程度主要通过认知功能、精神行为症状和日常生活能力来评估。目前，可用于治疗轻度至中度 AD 的药物选择不多，且药物的价值仍存在争议。
本研究旨在定量评估胆碱酯酶抑制剂（ChEIs）、美金刚和寡甘露糖（GV-971）治疗 AD 患者的疗效和安全性。此外，还将进行分子对接分析，以研究多奈哌齐、加兰他敏、利伐斯的明和美金刚与 AD 相关关键受体蛋白（包括β淀粉样蛋白（Abeta）、微管相关蛋白（MAP）、载脂蛋白 E4（APOE4）和线粒体融合蛋白-2（MFN2））的结合亲和力，以进一步验证荟萃分析的结果。
我们检索了 ChEIs、美金刚和 GV-971 的随机、安慰剂对照和双盲临床试验。使用 Review Manager Version 5.4 软件进行统计分析。还进行了分子对接以评估结果。
所有药物均改善了认知功能，效果值范围从 20mg 美金刚的-1.23（95%CI -2.17 至 -0.30）到 32mg 加兰他敏的-3.29（95%CI -4.14 至 -2.45）。虽然 32mg 美金刚和 GV-971 对临床医生的总体印象变化量表没有改善作用，但与安慰剂相比，其他药物均显示出显著效果。在 NPI 方面，只有 10mg 多奈哌齐和 24mg 加兰他敏有改善作用。在 ADCS/ADL 方面，只有 20mg 美金刚和 900mg GV-971 与安慰剂无显著差异。与安慰剂相比，5mg 多奈哌齐和 900mg GV-971 因各种原因或不良反应导致药物停药率没有增加。与其他药物相比，多奈哌齐对蛋白的结合具有更强的亲和力，表现出更好的疗效。
ChEIs、美金刚和 GV-971 均可减缓 AD 的进展，但对各自的评估效果不同。多奈哌齐和 GV-971 具有较好的耐受性。
