Defining circadian disruption in neurodegenerative disorders

Oct 1, 2021The Journal of clinical investigation

Understanding Daily Rhythm Disturbances in Brain Degeneration Disorders

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Abstract

Circadian disruption may be a core symptom of neurodegenerative diseases such as Alzheimer's, Huntington's, and Parkinson's.

Neurodegenerative diseases are characterized by misfolded proteins and the progressive loss of neurons.
Symptoms can vary, with some patients experiencing motor issues while others face cognitive and psychiatric challenges.
Disruption of the sleep/wake cycle is observed early in the disease trajectory and could be a risk factor for disease development.
Neurodegenerative processes may impair the structure and function of the circadian timing system.
Circadian-based interventions and timed drug treatments have the potential to improve symptoms associated with these disorders.
Key gaps in knowledge regarding circadian disruption and neurodegeneration are identified.

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Neurodegenerative diseases encompass a large group of conditions that are clinically and pathologically diverse yet are linked by a shared pathology of misfolded proteins. The accumulation of insoluble aggregates is accompanied by a progressive loss of vulnerable neurons. For some patients, the symptoms are motor focused (ataxias), while others experience cognitive and psychiatric symptoms (dementias). Among the shared symptoms of neurodegenerative diseases is a disruption of the sleep/wake cycle that occurs early in the trajectory of the disease and may be a risk factor for disease development. In many cases, the disruption in the timing of sleep and other rhythmic physiological markers immediately raises the possibility of neurodegeneration-driven disruption of the circadian timing system. The aim of this Review is to summarize the evidence supporting the hypothesis that circadian disruption is a core symptom within neurodegenerative diseases, including Alzheimer's disease, Huntington's disease, and Parkinson's disease, and to discuss the latest progress in this field. The Review discusses evidence that neurodegenerative processes may disrupt the structure and function of the circadian system and describes circadian-based interventions as well as timed drug treatments that may improve a wide range of symptoms associated with neurodegenerative disorders. It also identifies key gaps in our knowledge.

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Defining circadian disruption in neurodegenerative disorders

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