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  • Review Article
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Circadian rhythms in neurodegenerative disorders

Nature Reviews Neurology volume 18, pages 7–24 (2022)Cite this article

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Abstract

Endogenous biological clocks, orchestrated by the suprachiasmatic nucleus, time the circadian rhythms that synchronize physiological and behavioural functions in humans. The circadian system influences most physiological processes, including sleep, alertness and cognitive performance. Disruption of circadian homeostasis has deleterious effects on human health. Neurodegenerative disorders involve a wide range of symptoms, many of which exhibit diurnal variations in frequency and intensity. These disorders also disrupt circadian homeostasis, which in turn has negative effects on symptoms and quality of life. Emerging evidence points to a bidirectional relationship between circadian homeostasis and neurodegeneration, suggesting that circadian function might have an important role in the progression of neurodegenerative disorders. Therefore, the circadian system has become an attractive target for research and clinical care innovations. Studying circadian disruption in neurodegenerative disorders could expand our understanding of the pathophysiology of neurodegeneration and facilitate the development of novel, circadian-based interventions for these disabling disorders. In this Review, we discuss the alterations to the circadian system that occur in movement (Parkinson disease and Huntington disease) and cognitive (Alzheimer disease and frontotemporal dementia) neurodegenerative disorders and provide directions for future investigations in this field.

Key points

  • Numerous manifestations associated with Parkinson disease, Huntington disease, Alzheimer disease and frontotemporal dementia exhibit diurnal fluctuations, which might have circadian origins.

  • Neurodegenerative processes disrupt the structure and function of the circadian system.

  • Circadian disruption might be a risk factor for the development of neurodegenerative disorders.

  • Circadian-based interventions, such as timed light exposure, timed physical activity and melatonin, might improve some symptoms of neurodegenerative disorders and possibly affect the progression of neurodegeneration by restoring circadian homeostasis.

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Fig. 1: Organization of human circadian system.
Fig. 2: The relationships between circadian and sleep dysregulation and neurodegenerative disorders.

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Authors and Affiliations

  1. Division of Sleep Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Malik Nassan

  2. Mesulam Center for Cognitive Neurology, Northwestern University, Chicago, IL, USA

    Malik Nassan

  3. Division of Sleep Medicine, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Aleksandar Videnovic

  4. Division of Movement Disorders, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Aleksandar Videnovic

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Glossary

Actigraphy

An objective method of measuring motor activity as a proxy for rest and activity periods over days to weeks using a non-invasive accelerometer.

Mesor

A circadian rhythm-adjusted mean.

Acrophase

The time at which the peak of a rhythm occurs.

Phase advance

The onset of the cycle is advanced.

Sundowning

A set of symptoms characterized by confusion, anxiety, agitation or aggression, which usually occur in the late afternoon and early evening.

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Nassan, M., Videnovic, A. Circadian rhythms in neurodegenerative disorders. Nat Rev Neurol 18, 7–24 (2022). https://doi.org/10.1038/s41582-021-00577-7

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