促食欲素受体拮抗剂治疗阿尔茨海默病的潜在可能性及研究进展OA

Alzheimer disease(AD)is a neurodegenerative disease with the core pathological features of β-amyloid(Aβ)deposition and abnormal tau phosphorylation,and it is often comorbid with sleep disturbance,with the presence of bi-directional interactions between the two diseases.orexin is a key neurotransmitter in the regulation of sleep-wake cycles,and the potential of orexin receptor antagonists(ORAs)in improving insomnia has attracted more and more attention.This article reviews the mechanism of interaction between AD and sleep disturbance,with a focus on the effect on ORAs,especially dual orexin receptor antagonists(DORAs)such as Suvorexant and Lemborexant,on AD pathology and sleep disturbance by regu-lating the orexin signaling pathway.Clinical studies have shown that DORAs can significantly improve sleep quality in AD pa-tients by increasing total sleep time and reducing nocturnal awakenings and may reduce the levels of Aβ and phosphorylated tau protein in cerebrospinal fluid for a short period of time.However,current studies have the limitations of a small sample size and a short follow-up time,with insufficient evidence on the improvement in cognitive function and the presence of ad-verse reactions including somnolence.Future research should further explore the long-term efficacy and safety of ORAs in AD,in order to clarify the clinical value of ORAs in the comprehensive treatment of AD.