Circadian Rhythm Disruption in Alzheimer's Disease: Mechanistic Insights, Diagnostic Implications, and Emerging Chronotherapeutic Strategies: A Narrative Review
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disease with a complex etiology that involves environmental, genetic, and metabolic components. Among these, circadian rhythm disruption has been seen critical but underexplored component in the pathogenesis of Alzheimer's disease. The suprachiasmatic nucleus (SCN), the central pacemaker of circadian regulation, coordinates all the physiological processes, such as sleep-wake cycles, metabolism, and neuroendocrine signalling. Tau-pathology, neuroinflammation, amyloid-β build-up, and cognitive decline in Alzheimer's disease are all becoming gradually linked to dysregulation of the system. A detailed review of literature was performed to study the role of circadian disruption in Alzheimer's disease. Alzheimer's disease-related circadian rhythm dysregulation is expressed through decreased melatonin secretion, sleep disturbances, and modified SCN signalling. Neuronal dysfunction could be caused by mutations in important clock genes (BMAL1, PER, CRY, and CLOCK). Sleep deprivation increases the buildup of amyloid-β and impairs glymphatic clearance. Also, tau pathology interrupts the circadian clock, further speeding up cognitive decline. Chronotherapies involving melatonin supplementation, light therapy, environment, and sleep hygiene provide promising effects in restoring circadian regulation and enhancing cognitive performance. According to the research from both experimental and clinical studies, there is a link between…
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