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Important advances in sleep research in 2021

Leslie c west, clete a kushida.

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Issue date 2022 Jan.

Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Advances in sleep research in 2021 have brought about clinical developments for the next decade. Additionally, sleep telemedicine services have expanded rapidly, driven by the COVID-19 pandemic, to best serve patients with sleep disorders. 1 Here, we will explore some of the most impactful clinical studies from this field in 2021.

Progress has been made in evaluating the relationship between obstructive sleep apnoea and incidence of Alzheimer's disease. In a large cohort study of 53 321 patients with obstructive sleep apnoea, patients treated with continuous positive airway pressure (CPAP) were compared with those who were not. In adjusted models, those who were treated had a significantly lower odds of incident diagnosis of Alzheimer's disease or dementia (odds ratio 0·78, 95% CI 0·69–0·89). 2 This finding adds population-based evidence to suggest a temporal association between obstructive sleep apnoea treatment and dementia risk. In a study that analysed autopsy brains from 34 Icelandic patients with clinically verified obstructive sleep apnoea, Owen and colleagues 3 found that, as the severity of obstructive sleep apnoea increased, the burden of amyloid β in the hippocampus increased too, even after controlling for age, sex, body-mass index, and CPAP use. These findings, although in a small sample size, provide further neuropathological evidence for an association between Alzheimer's disease and obstructive sleep apnoea.

Throughout the COVID-19 pandemic, there have been reports of more frequent sleep disturbances. Morin and colleagues 4 conducted a multicentre survey of 22 330 adults from 13 countries and found that more than 35% of respondents reported insomnia symptoms, with about 17% meeting criteria for a probable insomnia disorder during the first months of the pandemic. These data provide an indication of the need for programmes to tackle insomnia during a global crisis. Arnedt and colleagues 5 reported findings of a placebo-controlled randomised trial of 65 adults assigned to telemedicine or in-person delivery of cognitive behavioural therapy for insomnia. They showed that cognitive behaviour therapy delivered via telemedicine was non-inferior to therapy done in-person, according to the reduction in insomnia severity index score.

Dual orexin receptor antagonists have been evaluated in clinical research as an additional treatment option for insomnia. 12-month results from the phase 3 analysis of the Study of the Efficacy and Safety of Lemborexant in Subjects 55 and Older with Insomnia Disorder (SUNRISE 2) were published in 2021. 6 This international, multicentre, randomised, double-blind, placebo-controlled, parallel-group study compared two doses of lemborexant (5 mg and 10 mg) with placebo, and enrolled 949 participants, including 318 who received placebo. Patients randomly assigned to treatment showed a benefit, with shorter sleep onset latency, increased subjective total sleep time, and decreased subjective wake after sleep onset, at 12-month follow-up.

Dauvilliers and colleagues 7 conducted a phase 3 randomised controlled trial of lower-sodium oxybate for the treatment of patients with idiopathic hypersomnia. They found a significant change in the Epworth Sleepiness Scale compared with placebo (difference of –6·5, 95% CI –8·0 to –5·0), indicating a clinically meaningful effect on excessive daytime sleepiness. Overall idiopathic hypersomnia symptom severity showed significant improvement in patients randomly assigned to lower-sodium oxybate compared with placebo.

Gaspar and colleagues 8 examined the effect of obstructive sleep apnoea on disruption of circadian rhythms. Their study was the first to compare the effect of CPAP in the short term (4 months) and long term (2 years) on circadian characteristics in a case-control study of 34 male patients with obstructive sleep apnoea and seven age-matched and sex-matched healthy controls. The investigators found that long-term, but not short-term, CPAP treatment was able to re-establish levels of major clock circadian outputs, including plasma melatonin, cortisol, and body temperature. The authors found that CPAP does not fully re-establish the expression profile of clock genes, but leads to evident improvements.

Regarding public health policy, further evidence was published from the Changing Start Times: Longitudinal Effects Study (CaSTLES) evaluating school start times at or after 0830 h for middle-school and high-school students. 9 The findings showed that, when start times were 40–70 min later, middle-school students obtained an extra 2·4 h of sleep per week and high-school students an extra 3·8 h of sleep per week, with maintenance of this effect over 2 years.

In basic sleep science research, Konkoly and colleagues 10 provided proof-of-concept evidence that individuals can be interviewed about their dreams while they are dreaming. In four independent laboratories in France, Germany, the Netherlands, and the USA, healthy participants and one patient with narcolepsy provided evidence for real-time communication during rapid eye movement (REM) sleep. This example of bidirectional communication during REM sleep showed the use of working memory, with yet-to-be explored potential clinical applications for cognitive improvement, learning, and beyond.

In conclusion, the advances during this year have included a broad landscape of investigations, while researchers and clinical teams adapted to the challenge of conducting studies during a pandemic, and provided far-reaching new insights for sleep medicine.

CAK reports personal fees related to consultancies or participation in medical advisory boards from XW Pharma, Idorsia, Merck, Jazz Pharmaceuticals, Avadel Pharmaceuticals, Cerebra, and VIVOS; grants or contracts with the National Institutes of Health, Avadel Pharmaceuticals, AmCad BioMed Corporation, Jazz Pharmaceuticals, Merck Sharp & Dohme, Parexel International Corporation, Asate, Inspire Medical Systems, and Respironics; lecture honoraria from ResMed Asia and Itamar Medical; and stock or stock options from M3 Public Benefit Corporation, Restful Robotics, VIVOS, and Koko. LCW declares no competing interests.

• 1. Shamim-Uzzaman QA, Bae CJ, Ehsan Z, et al. The use of telemedicine for the diagnosis and treatment of sleep disorders: an American Academy of Sleep Medicine update. J Clin Sleep Med. 2021;17:1103–1107. doi: 10.5664/jcsm.9194. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
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• 4. Morin CM, Bjorvatn B, Chung F, et al. Insomnia, anxiety, and depression during the COVID-19 pandemic: an international collaborative study. Sleep Med. 2021;87:38–45. doi: 10.1016/j.sleep.2021.07.035. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
• 5. Arnedt JT, Conroy DA, Mooney A, Furgal A, Sen A, Eisenberg D. Telemedicine versus face-to-face delivery of cognitive behavioral therapy for insomnia: a randomized controlled noninferiority trial. Sleep. 2021;44 doi: 10.1093/sleep/zsaa136. [ DOI ] [ PubMed ] [ Google Scholar ]
• 6. Yardley J, Kärppä M, Inoue Y, et al. Long-term effectiveness and safety of lemborexant in adults with insomnia disorder: results from a phase 3 randomized clinical trial. Sleep Med. 2021;80:333–342. doi: 10.1016/j.sleep.2021.01.048. [ DOI ] [ PubMed ] [ Google Scholar ]
• 7. Dauvilliers Y, Arnulf I, Foldvary-Schaefer N, et al. Safety and efficacy of lower-sodium oxybate in adults with idiopathic hypersomnia: a phase 3, placebo-controlled, double-blind, randomised withdrawal study. Lancet Neurol. 2022;21:53–65. doi: 10.1016/S1474-4422(21)00368-9. [ DOI ] [ PubMed ] [ Google Scholar ]
• 8. Gaspar LS, Hesse J, Yalçin M, et al. Long-term continuous positive airway pressure treatment ameliorates biological clock disruptions in obstructive sleep apnea. EBioMedicine. 2021;65 doi: 10.1016/j.ebiom.2021.103248. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
• 9. Meltzer LJ, Wahlstrom KL, Plog AE, Strand MJ. Changing school start times: impact on sleep in primary and secondary school students. Sleep. 2021;44 doi: 10.1093/sleep/zsab048. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
• 10. Konkoly KR, Appel K, Chabani E, et al. Real-time dialogue between experimenters and dreamers during REM sleep. Curr Biol. 2021;31:1417–1427. doi: 10.1016/j.cub.2021.01.026. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ]
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The importance of sleep regularity: a consensus statement of the National Sleep Foundation sleep timing and variability panel

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Conclusions

• Sleep patterns
• Circadian misalignment
• Catch-up sleep
• Performance

Introduction

Development of the questions, participants and procedures, panel deliberations and consensus voting.

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Literature review

Limitations

Credit author statement, acknowledgments, declaration of conflict of interest, appendix a supplementary material (1).