The sleep and circadian problems of Huntington’s Disease: When, why and their importance

Zanna Voysey, Shaline V. Fazal, Alpar Lazar, Roger A. Barker

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Abstract

Introduction
Mounting evidence supports the existence of an important feedforward cycle between sleep and neurodegeneration, wherein neurodegenerative diseases cause sleep and circadian abnormalities, which in turn exacerbate and accelerate neurodegeneration. If so, sleep therapies bear important potential to slow progression in these diseases.

Findings
This cycle is challenging to study, as its bidirectional nature renders cause difficult to disentangle from effect. Likewise, well-controlled intervention studies are often impractical in the setting of established neurodegenerative disease. It is this that makes understanding sleep and circadian abnormalities in Huntington’s disease (HD) important: as a monogenic fully penetrant neurodegenerative condition presenting in midlife, it provides a rare opportunity to study sleep and circadian abnormalities longitudinally, prior to and throughout disease manifestation, and in the absence of confounds rendered by age and comorbidities. It also provides potential to trial sleep therapies at a preclinical or early disease stage. Moreover, its monogenic nature facilitates the development of transgenic animal models through which to run parallel pre-clinical studies. HD, therefore, provides a key model condition through which to gain new insights into the sleep-neurodegeneration interface.

Conclusions
Here, we begin by summarising contemporary knowledge of sleep abnormalities in HD, and consider how well these parallel those of Alzheimer’s and Parkinson’s as more common neurodegenerative conditions. We then discuss what is currently known of the sleep-neurodegeneration cyclical relationship in HD. We conclude by outlining key directions of current and future investigation by which to advance the sleep-neurodegeneration field via studies in HD.
Original languageEnglish
Pages (from-to)2275–2283
Number of pages9
JournalJournal of Neurology
Volume268
Issue number6
Early online date23 Dec 2020
DOIs
Publication statusPublished - Jun 2021

Keywords

  • Circadian rhythm
  • Dementia
  • Huntington’s disease
  • Neurodegeneration
  • Sleep

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