Effect of melatonin on cognitive function in adults with cognitive impairment: a multi-dimensional meta-analysis of randomized trials

Background: Cognitive impairment leads to poor daily social and occupational functions and sleep disturbances. Approximately two-thirds of all individuals with mild cognitive impairment (MCI) experience sleep problems that further reduce cognitive function. Melatonin, a hormone secreted by the pineal gland, has proven effective in mitigating sleep problems and cognitive function in individuals with MCI. The current review investigated the efficacy of melatonin in improving cognitive function in adults with cognitive impairment. Methods: Seven databases were systematically searched for relevant randomized controlled trials published (in English or Chinese) until April 2025. Two reviewers independently selected studies, assessed quality (using the Physiotherapy Evidence Database scale), and extracted data. Results: In total, 394 potentially eligible articles were identified. Finally, 8 studies (518 participants) were included. Five, one, and two studies had good, excellent, and low quality, respectively. Pooled results indicated that melatonin significantly improved cognitive function in adults with cognitive impairment (mean difference [MD]: 1.08; p < 0.0001). Subgroup analyses by treatment duration, administration time, and cognitive impairment level revealed that the effects of melatonin were significant when it was administered for 13–24 weeks (MD: 2.04; p < 0.00001), between the times of 20:30 and 21:00 (MD: 2.2; p < 0.00001), and to individuals with MCI (MD: 2.63; p < 0.000001). Conclusions: Our findings suggest that melatonin is relatively safe for individuals with cognitive impairment. Thus, we recommend it for adults with MCI. It should be administered between 20:30 and 21:00 for 13–24 weeks.