Circadian Rhythm Sleep–Wake Disorders: a Contemporary Review of Neurobiology, Treatment, and Dysregulation in Neurodegenerative Disease

Circadian rhythms oscillate throughout a 24-h period and impact many physiological processes and aspects of daily life, including feeding behaviors, regulation of the sleep-wake cycle, and metabolic homeostasis. Misalignment between the endogenous biological clock and exogenous light–dark cycle can cause significant distress and dysfunction, and treatment aims for resynchronization with the external clock and environment. This article begins with a brief historical context of progress in the understanding of circadian rhythms, and then provides an overview of circadian neurobiology and the endogenous molecular clock. Various tools used in the diagnosis of circadian rhythm sleep–wake disorders, including sleep diaries and actigraphy monitoring, are then discussed, as are the therapeutic applications of strategically timed light therapy, melatonin, and other behavioral and pharmacological therapies including the melatonin agonist tasimelteon. Management strategies towards each major human circadian sleep–wake rhythm disorder, as outlined in the current International Classification of Sleep Disorders – Third Edition, including jet lag and shift work disorders, delayed and advanced sleep–wake phase rhythm disorders, non-24-h sleep–wake rhythm disorder, and irregular sleep–wake rhythm disorder are summarized. Last, an overview of chronotherapies and the circadian dysregulation of neurodegenerative diseases is reviewed.