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July 11, 2022

Targeting Sleep and Circadian Function in the Prevention of Alzheimer Disease

Author Affiliations
  • 1Department of Neurology, Washington University School of Medicine, St Louis, Missouri
  • 2Center on Biological Rhythms and Sleep (COBRAS), Washington University School of Medicine, St Louis, Missouri
JAMA Neurol. 2022;79(9):835-836. doi:10.1001/jamaneurol.2022.1732

The accelerating pace of research on sleep or circadian function and Alzheimer disease (AD) has raised the possibility of targeting sleep or circadian behaviors to mitigate AD risk. Sleep and circadian functions are separate but intertwined, in that circadian mechanisms coordinate physiological functions to the 24-hour clock for optimal function, including sleep-wake state. Accumulating data support a bidirectional association between AD pathology and sleep and circadian function. Even during the more than 15-year preclinical (presymptomatic) stage of AD, decreased sleep quality and fragmented circadian rhythms are associated with AD pathology.1,2 Conversely, sleep and circadian dysfunction, particularly slow-wave sleep disruption, elevates levels of amyloid-β and tau.3-5 Large longitudinal studies show that obstructive sleep apnea (OSA) and insufficient sleep increase risk of cognitive impairment.6,7 Given the high prevalence of sleep and circadian dysfunction, with an estimated 1 billion individuals worldwide having OSA, and 40% in a large survey conducted in the UK reporting insufficient sleep,7 sleep and circadian function may be a high-value target for intervention as a modifiable AD risk factor.

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1 Comment for this article
Sleep and Alzheimer Disease - Take Care with the Eyes
Peter Shah, BSc MA FRCOphth FRCP Edin | University Hospitals Birmingham NHS Foundation Trust
The influence of sleep and circadian function on susceptibility to and progression of Alzheimer disease is a fascinating area of hope in this devastating disease. As this area opens up with new potential treatments, it is important to consider the impact of co-existing eye disease in this complex neuro-ophthalmic area.

As an example, glaucoma can have a profound impact on sleep quality and circadian rhythm. Glaucoma is a common optic neuropathy characterised by loss of retinal ganglion cells (RGCs), the majority of which are involved in the generation of cortical images. However, about 3% of the RGC population express
melanopsin and are specialised into other areas of non-visual activity, such as modulation of circadian rhythm and pupillary light reflexes.

It is intriguing to think that the health of this relatively small population of intraocular intrinsically photosensitive retinal ganglion cells (ipRGCs) may play a part in maintenance of our cognition.