'The clocks that time us'--circadian rhythms in neurodegenerative disorders.
Circadian rhythms are physiological and behavioural cycles generated by an endogenous biological clock, the suprachiasmatic nucleus. The circadian system influences the majority of physiological processes, including sleep-wake homeostasis. Impaired sleep and alertness are common symptoms of neurodegenerative disorders, and circadian dysfunction might exacerbate the disease process. The pathophysiology of sleep-wake disturbances in these disorders remains largely unknown, and is presumably multifactorial. Circadian rhythm dysfunction is often observed in patients with Alzheimer disease, in whom it has a major impact on quality of life and represents one of the most important factors leading to institutionalization of patients. Similarly, sleep and circadian problems represent common nonmotor features of Parkinson disease and Huntington disease. Clinical studies and experiments in animal models of neurodegenerative disorders have revealed the progressive nature of circadian dysfunction throughout the course of neurodegeneration, and suggest strategies for the restoration of circadian rhythmicity involving behavioural and pharmacological interventions that target the sleep-wake cycle. In this Review, we discuss the role of the circadian system in the regulation of the sleep-wake cycle, and outline the implications of disrupted circadian timekeeping in neurodegenerative diseases.
Neurological Clinical Research Institute, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 165 Cambridge Street Suite 650, Boston, MA 02114, USA.
Aleksandar
A
Videnovic
University of Cambridge, John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, Forvie Site, Cambridge CB2 2PY, UK.
Alpar S
AS
Lazar
University of Cambridge, John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, Forvie Site, Cambridge CB2 2PY, UK.
Roger A
RA
Barker
Department of Neurology, Radboud University Medical Centre, P.O. Box 9101, Nijmegen 6500 HB, Netherlands.
Sebastiaan
S
Overeem
D000818:Animals; D057906:Circadian Clocks / Q000502:physiology*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000503:physiopathology*