Comparative Efficacy, Tolerability, and Acceptability of Donanemab, Lecanemab, Aducanumab, Melatonin, and Aerobic Exercise for a Short Time on Cognitive Function in Mild Cognitive Impairment and Mild Alzheimer's Disease: A Systematic Review and Network Meta-Analysis.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
melatonin administration | increase | cognitive function | people with mild AD and MCI | - | significantly more effective than donanemab, lecanemab, aducanumab and placebo | #1 |
aerobic exercise for a short time | increase | cognitive function | people with mild AD and MCI | - | significantly more effective than donanemab, lecanemab, aducanumab and placebo | #2 |
melatonin | increase | cognitive function | people with mild AD and MCI | - | significantly more effective than donanemab, lecanemab, aducanumab and placebo | #3 |
aerobic exercise for a short time | decrease | acceptability | people with mild AD and MCI | - | significantly less acceptable than donanemab, aducanumab and placebo | #4 |
donanemab | decrease | tolerability | people with mild AD and MCI | - | significantly less tolerable than placebo | #5 |
lecanemab | decrease | tolerability | people with mild AD and MCI | - | significantly less tolerable than placebo | #6 |
aducanumab | decrease | tolerability | people with mild AD and MCI | - | significantly less tolerable than placebo | #7 |
donanemab | decrease | acceptability | people with mild AD and MCI | - | significantly less acceptable than placebo | #8 |
lecanemab | decrease | acceptability | people with mild AD and MCI | - | significantly less acceptable than placebo | #9 |
aerobic exercise for a short time | increase | cognitive decline | people with mild AD and MCI | - | might also be better than donanemab, lecanemab and aducanumab if continued | #10 |
BACKGROUND: 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. OBJECTIVE: 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. METHODS: We systematically reviewed relevant randomized placebo-controlled trials (RCTs) in PubMed, the Cochrane Library, CINHAL, and ClinicalTrials.gov and performed network meta-analyses. RESULTS: 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. CONCLUSIONS: 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.