Sleep Disorders and Circadian Rhythms*

Date/Time: Monday, September 11, 2023 - 4:15 PM – 5:45 PM
Track: Special Interest Group (SIG) Session
Room: Salons C-D (5th Floor)
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Chair: Sabra Abbott, MD, PhD

Co-Chair: Brendan Lucey, MD

This session will highlight state of the art research in the area of sleep and circadian rhythm disorders that is relevant for researchers and practicing clinicians.

Learning Objectives:

  • Define sleep and circadian disruption.
  • Recognize the role of this disruption in the pathophysiology of neurological disorders.
  • Use strategies aimed at optimizing sleep and circadian health as a tool for neurological disease treatment and prevention.

Bidirectional Role of Sleep and Stroke

Speaker: Eric Landsness, MD, PhD

There is a bidirectional relationship between stroke disrupting sleep and how sleep disorders increase the risk of stroke.  This talk will discuss the evidence to date, how it affects clinical practice and the latest advances in the science of understanding sleep and stroke.

Circadian Rhythms in Neurodegenerative Disorders

Speaker: Aleksander Videnovic, MD, MSc, FANA

Endogenous biological clocks time the circadian rhythms that synchronize human physiology and behavior. Disruption of circadian homeostasis has deleterious effects on human health. Neurodegenerative disorders involve a wide range of symptoms and many exhibit diurnal variations in frequency and intensity. These disorders also disrupt circadian homeostasis, which negatively affects symptoms and quality of life. Emerging evidence points to a bidirectional relationship between circadian homeostasis and neurodegeneration, suggesting that circadian function might be important in the progression of neurodegenerative disorders. Therefore, the circadian system has become an attractive target for research and clinical care innovations. In this presentation, we discuss the alterations to the circadian system that occur in neurodegenerative disorders and provide directions for future investigations in this field.

The Impact of CPAP Therapy for 4 Months for Management of SRBDs on Psychosocial Outcomes in Individuals with Chronic Spinal Cord Injury: A Mixed-Methods Study

Oral Abstract Presenter: Julio Furlan, MD, LLB, MBA, PhD, MSc, FRCPC

Background: Sleep-related breathing disorders (SRBDs) are common but under-recognized after spinal cord injury (SCI). We report preliminary data from an ongoing study examining the potential psychosocial benefits of continuous positive airway pressure (CPAP) therapy in people with SCI and moderate-to-severe SRBDs. Methods: This single-arm clinical trial (NCT04007380) aims to evaluate the impact of 4 months of CPAP therapy among adults with chronic SCI who were newly diagnosed with moderate-to-severe SRBDs. Outcome measures included Epworth Sleepiness Scale (ESS), Medical Outcomes Study Sleep Scale (MOS-SS), Fatigue Severity Scale (FSS), Depression, Anxiety & Stress Scale-21 (DASS-21), Montreal Cognitive Assessment (MoCA), SF-36, and Craig Handicap Assessment & Reporting Technique (CHART). All participants were invited for a semi-structured interview to share their experience after the trial (qualitative analysis). Adherence was defined as the use of CPAP for ≥4 hours/night on ≥5 nights of the week. Results: By February/2023, we screened 33 individuals (10 females, 23 males; ages range: 37-79 years; mean age: 58.3 years) with complete (n=15) or incomplete SCI at the cervical (n=22) or thoracic level. Mean time from SCI onset was 180.3 months (range: 4-793 months). Of the 33 screened participants, the apnea-hypopnea index (AHI) varied from 2.6 to 83.7 events/hour (mean AHI: 24.6), and 25 individuals with moderate-to-severe SRBDs initiated CPAP therapy. Overall, 19 individuals have completed the trial, whereas 8 individuals withdrew from the study. The overall mean adherence rate to CPAP was 42.1% among those who completed the trial. Daytime sleepiness and sleep quality significantly improved with CPAP therapy (pre-ESS=9.4, post-ESS=4.9, p=0.0002; pre-MOS-SS=27.9, post-MOS-SS=57.9, p<0.0001). The FSS also significantly decreased with CPAP therapy (pre-FSS=44.0, post-FSS=34.9, p=0.0194). Health-related quality of life also significantly improved after CPAP therapy (SF-36 physical component summary: p=0.0104; SF-36 mental component summary: p=0.00561). There was a numeric increase in MoCA, DASS-21 and CHART scores, but they did not yet reach significance (MoCA: p=0.079; DASS-21: p=0.207; CHART: p=0.221). Notably, the DASS-21 anxiety subscore significantly reduced with CPAP therapy (p=0.043). All 19 participants confirmed that CPAP therapy had a major beneficial impact on psychosocial outcomes in the qualitative study. Conclusions: Our preliminary results suggest that 4-month CPAP therapy significantly improves sleep quality, and quality of life, and mitigates daytime sleepiness, fatigue, and anxiety in people with chronic SCI. These findings were corroborated by the results of the qualitative analysis.

COVID-19 Disrupts Sleep Architecture by Reducing N3 Stage Sleep

Oral Abstract Presenter: Sung Ji, MD, PhD

Coronavirus disease 2019 (COVID-19) is an infection caused by Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV2) that has led to the most devastating global pandemic in recent history, causing more than 6 million deaths globally. Despite its primary association with respiratory symptoms, nervous system involvement of COVID-19 was recognized early on. Neurologic complications during acute SARS-CoV2 infection were associated with a higher risk for persistent morbidity and mortality. There is interest in understanding the long-term neurologic consequences of COVID-19, as more patients report chronic sequelae of COVID-19 (termed Post-Acute Sequelae of COVID-19 [PASC]). Among the neurologic symptoms of PASC, sleep disturbance has been consistently endorsed in clinical settings and cohort studies, but these symptoms are largely based on subjective reports. How COVID-19 impacts sleep architecture has not been examined in a quantitative manner. To address this, we performed a retrospective study of available polysomnography (PSG) data from adult patients within the University of Washington Medicine who had at least 2 sets of PSG studies done. COVID-19 participants (n = 9) had one PSG study at least 1 month after COVID-19 (verified with positive SARS-CoV2 PCR) and another PSG study at least 1 month prior to COVID-19. For controls (n = 24; matched to COVID-19 participants for age, gender, body mass index, comorbidities and duration between studies), PSG data were taken from studies performed before January 2020, in order to eliminate any possibility of prior SARS-CoV2 infection. All PSG tests in this study were obtained for the purposes of monitoring responses to sleep apnea treatment. We found that COVID-19 patients developed a significant decrease in percentage of N3 stage sleep in their post-COVID-19 study compared to their pre-COVID-19 study (p = 0.001) despite similar total sleep duration and latency. To assess if these changes were truly due to SARS-CoV2 infection, our COVID-19 PSG data were compared to pre-pandemic matched control data. This demonstrated that over a similar time period, the percentage of N3 stage sleep significantly decreased in COVID-19 patients (-80.6 ± 8.4%) in contrast to the controls who showed an increase (+62.9 ± 23.6 %; p = 0.0009). This is one of the first study to demonstrate how COVID-19 impacts sleep architecture using PSG data. Given that reduced N3 stage sleep can contribute to the development of chronic fatigue syndrome and neurodegenerative diseases, these changes may have important implications for explaining the mechanisms underlying the neurologic symptoms of PASC.

Sleep Insufficiency, Circadian Rhythms, and Metabolomics: The Connection to Metabolic Sleep Disorders

Oral Abstract Presenter: Katherine Russell, MSPH

Purpose: The majority of US adults who report experiencing insufficient sleep are more likely to suffer from metabolic disorders such as hyperlipidemia, diabetes, and obesity than those with sufficient sleep. Less is understood about the underlying molecular mechanisms connecting these phenomena. A systematic, qualitative review of metabolomics studies exploring metabolic changes in response to sleep insufficiency, sleep deprivation, or circadian disruption was conducted in accordance with PRISMA guidelines. Methods: An electronic literature review in the PubMed database was performed considering publications through May 2021 and screening and eligibility criteria were applied to articles retrieved. The following keywords were used: “metabolomics” and “sleep disorders” or “sleep deprivation” or “sleep disturbance” or “circadian rhythm.” After screening and addition of studies included from reference lists of retrieved studies, 16 records were identified for review. Results: Consistent changes in metabolites were observed across studies between individuals experiencing sleep deprivation as compared to non-sleep deprivation controls. Significant increases in phosphatidylcholines, acylcarnitines, sphingolipids, and other lipids are consistent across studies. Increased levels of amino acids such as tryptophan and phenylalanine are also noted. However, studies are limited to small samples of young, healthy, mostly male participants conducted in short inpatient sessions, limiting generalizability. Conclusion: Changes in lipid and amino acid metabolites accompanying sleep deprivation and/or circadian rhythms may indicate cellular membrane and protein breakdown underlying the connection between sleep disturbance, hyperlipidemia, and other metabolic disorders. Larger epidemiological studies examining changes in the human metabolome in response to chronic insufficient sleep would help elucidate this relationship.