Effect and Mechanism of Exogenous Melatonin on Cognitive Deficits in Animal Models of Alzheimer's Disease: A Systematic Review and Meta-analysis.

Melatonin (MT) has been reported to control and prevent Alzheimer's disease (AD) in the clinic; however, the effect and mechanism of MT on AD have not been specifically described. Therefore, the main purpose of this meta-analysis was to explore the effect and mechanism of MT on AD models by studying behavioural indicators and pathological features. Seven databases were searched and 583 articles were retrieved. Finally, nine studies (13 analyses, 294 animals) were included according to pre-set criteria. Three authors independently judged the selected literature and the methodological quality. Meta-analysis showed that MT markedly ameliorated the learning ability by reducing the escape latency, and the memory deficit was significantly corrected by increasing the dwell time in the target quadrant and crossings over the platform location in the Morris Water Maze (MWM). Among the pathological features, subgroup analysis found that MT may ease the symptoms of AD mainly by reducing the deposition of Aβ40 and Aβ42 in the cortex. In addition, MT exerted a superior effect on ameliorating the learning ability of senescence-related and metabolic AD models, and corrected the memory deficit of the toxin-induced AD model. The study was registered at PROSPERO (CRD42021226594).