Role of suvorexant in Alzheimer's disease: Targeting sleep, orexin signaling, and disease pathophysiology

The defining features of Alzheimer's disease (AD) include neurodegeneration, a decline in cognition, and tau and amyloid-β protein pathologies. Sleep problems affect many individuals with AD and could be an aggravating factor in the disease because it creates a barrier to the glymphatic system's ability to clear neurotoxic proteins, disrupt the plasticity of synapses, and increase neuroinflammation. Suvorexant, which works as a dual orexin receptor antagonist, has proven effective in the management of sleep problems by fine-tuning the orexin system, which regulates arousal. Preliminary studies indicate that, in addition to improving sleep, Suvorexant could potentially help in the reduction of amyloid and tau buildup, as well as the improvement of synaptic activity and reduction of neuroinflammation. Recent clinical studies show improvements in sleep quality among older adults, in addition to safety and efficacy, and suggest increasing cognitive functioning in mild cognitive impairment and early AD. This review summarizes the existing research on the potential of Suvorexant as a therapeutic to address the mechanisms of orexin signaling in AD, as well as the sleep-targeted interventions to address the symptoms and modify the disease to improve cognitive functioning. We also emphasize future research directions such as cognitive outcomes over extended periods, potential optimal dosing, and combinatory strategies with lifestyle and/or medication therapies. This review will discuss the current evidence regarding the therapeutic effects of suvorexant and orexin signaling in AD.