Terao Itsuki, Kodama Wakako
Department of Psychiatry, Ikokoro Clinic Nihonbashi, Tokyo, Japan.
Department of Psychiatry, Negishi Hospital, Tokyo, Japan.
J Alzheimers Dis. 2024;98(3):825-835. doi: 10.3233/JAD-230911.
The Food and Drug Administration (FDA) has approved lecanemab and aducanumab and is reviewing donanemab, but they have questionable efficacy, serious side effects and are costly, whereas melatonin administration and aerobic exercise for a short time may overcome these problems.
We aim to compare the efficacy on cognitive function, tolerability and acceptability of melatonin administration and aerobic exercise for a short time with donanemab, lecanemab, and aducanumab in people with mild AD and MCI.
We systematically reviewed relevant randomized placebo-controlled trials (RCTs) in PubMed, the Cochrane Library, CINHAL, and ClinicalTrials.gov and performed network meta-analyses.
The analysis included 10 randomized placebo-controlled trials with 4,599 patients. Although melatonin and aerobic exercise for a short time were significantly more effective than donanemab, lecanemab, aducanumab and placebo in the primary analysis, there was significant heterogeneity. In the sensitivity analysis excluding exercise, melatonin was significantly more effective than donanemab, lecanemab, aducanumab and placebo, with no significant heterogeneity. Aerobic exercise for a short time was significantly less acceptable than donanemab, aducanumab and placebo. Donanemab, lecanemab, and aducanumab were significantly less tolerable than placebo and donanemab and lecanemab were significantly less acceptable than placebo.
Melatonin may be a better potential disease-modifying treatment for cognitive decline in mild AD and MCI. Aerobic exercise for a short time might also be better than donanemab, lecanemab and aducanumab if continued, as it is well tolerated and more effective, although less valid due to heterogeneity. Another limitation is the small number of participants.
美国食品药品监督管理局（FDA）已批准了lecanemab和aducanumab，并正在审评donanemab，但它们的疗效存疑、有严重副作用且成本高昂，而短期服用褪黑素和进行有氧运动可能会克服这些问题。
我们旨在比较短期服用褪黑素和进行有氧运动与donanemab、lecanemab和aducanumab对轻度阿尔茨海默病（AD）和轻度认知障碍（MCI）患者认知功能、耐受性和可接受性的疗效。
我们在PubMed、考克兰图书馆、CINHAL和ClinicalTrials.gov上系统检索了相关的随机安慰剂对照试验（RCT），并进行网状Meta分析。
该分析纳入了10项随机安慰剂对照试验，共4599例患者。虽然在初步分析中，短期服用褪黑素和进行有氧运动比donanemab、lecanemab、aducanumab和安慰剂显著更有效，但存在显著异质性。在排除运动的敏感性分析中，褪黑素比donanemab、lecanemab、aducanumab和安慰剂显著更有效，且无显著异质性。短期有氧运动的可接受性显著低于donanemab、aducanumab和安慰剂。Donanemab、lecanemab和aducanumab的耐受性显著低于安慰剂，且donanemab和lecanemab的可接受性显著低于安慰剂。
褪黑素可能是治疗轻度AD和MCI认知功能下降的更有潜力的疾病改善疗法。如果持续进行，短期有氧运动可能也比donanemab、lecanemab和aducanumab更好，因为它耐受性良好且更有效，尽管由于异质性有效性较低。另一个局限性是参与者数量较少。
