Associations of sleep and circadian phenotypes with COVID-19 susceptibility and hospitalization: an observational cohort study based on the UK Biobank and a two-sample Mendelian randomization study

Study Objectives Sleep and circadian phenotypes are associated with several diseases. The present study aimed to investigate whether sleep and circadian phenotypes were causally linked with coronavirus disease 2019 (COVID-19)-related outcomes. Methods Habitual sleep duration, insomnia, excessive daytime sleepiness, daytime napping, and chronotype were selected as exposures. Key outcomes included positivity and hospitalization for COVID-19. In the observation cohort study, multivariable risk ratios (RRs) and their 95% confidence intervals (CIs) were calculated. Two-sample Mendelian randomization (MR) analyses were conducted to estimate the causal effects of the significant findings in the observation analyses. Beta values and the corresponding 95% CIs were calculated and compared using the inverse variance weighting, weighted median, and MR-Egger methods. Results In the UK Biobank cohort study, both often excessive daytime sleepiness and sometimes daytime napping were associated with hospitalized COVID-19 (excessive daytime sleepiness [often vs. never]: RR=1.24, 95% CI=1.02-1.5; daytime napping [sometimes vs. never]: RR=1.12, 95% CI=1.02-1.22). In addition, sometimes daytime napping was also associated with an increased risk of COVID-19 susceptibility (sometimes vs. never: RR= 1.04, 95% CI=1.01-1.28). In the MR analyses, excessive daytime sleepiness was found to increase the risk of hospitalized COVID-19 (MR IVW method: OR = 4.53, 95% CI = 1.04-19.82), whereas little evidence supported a causal link between daytime napping and COVID-19 outcomes. Conclusions Observational and genetic evidence supports a potential causal link between excessive daytime sleepiness and an increased risk of COVID-19 hospitalization, suggesting that interventions targeting excessive daytime sleepiness symptoms might decrease severe COVID-19 rate.

Excessive Daytime Sleepiness Is Associated With Non-motor Symptoms of Multiple System Atrophy: A Cross-Sectional Study in China

Objectives: Excessive daytime sleepiness (EDS) in multiple system atrophy (MSA) has received scant attention in the literature, thus the present cross-sectional study aimed to investigate the prevalence of EDS and its potential risk factors among Chinese patients with MSA.Methods: A total of 66 patients with MSA (60.6% males) were consecutively recruited. Eighteen patients (27.3%, 13 men) with Epworth Sleepiness Scale score >10 were defined as having EDS. Demographic, motor [Unified Multiple-System Atrophy (UMSARS)] and non-motor symptoms [Non-Motor Symptoms Scale (NMSS)], and sleep parameters [polysomnography (PSG)] were compared between patients with MSA with and without EDS. A logistic regression analysis was used to calculate the risk factors of EDS in patients with MSA.Results: There were no significant differences in age, sex, MSA onset age, disease duration, MSA sub-type, and motor symptom severity between MSA patients with and without EDS. However, compared with the MSA patients without EDS, their counterparts with EDS had higher scores of NMSS (65.3 ± 23.1 vs. 43.4 ± 25.3, P = .0002), Hamilton Anxiety (HAMA) [15.3 (10.3–20.0) vs. 9.5 (3.0–15.0), P = 0.006], Hamilton Depression (HAMD) [13.7 (12.5–17.8) vs. 9.0 (4.0–13.0), P = 0.015], and Fatigue Severity Scale (FSS) [29.8 (17.3–47.8) vs. 18.7 (10.3–21.8), P = 0.040]. Conversely, the patients with EDS had lower score of Mini-Mental State Examination (MMSE) [23.3 (20.3–27.0) vs. 25.7 (22.0–29.0), P = 0.023]. Similarly, there was a significantly lower percentage of N3 sleep (%) [0.3 (0–0) vs. 2.0 (0–0), P = 0.007] and a higher apnea-hypopnea index (AHI/h) [30.5 (14.5–47.8) vs. 19.3 (5.0–28.7), P = 0.034] in patients with EDS. After adjusting for age, sex, disease duration, MSA sub-type, and UMSARS score, the odds ratio (OR) (95% CI) of EDS was higher while increasing scores in FSS [1.06 (1.02–1.11)], HAMA [1.16 (1.04–1.28)], HAMD [1.13 (1.02–1.25)], NMSS [1.04 (1.01–1.07)], and AHI [1.03 (1.00–1.10)]. The OR of EDS was lower while the MMSE score was increasing [0.85 (0.72–1.00)].Conclusions: The presence and severity of EDS may be significantly associated with the non-motor dysfunction, including fatigue, anxiety, depression, cognitive dysfunction, and sleep-related breathing disorder, but not with the motor dysfunction in MSA.

Early Daytime Sleepiness and Nighttime Slow-wave Sleep Disorganization in Progressive Macaque Model of Parkinson’s Disease

Parkinsonian patients often experience wake/sleep behavior disturbances, which can appear at an early stage of the disease in a way that is still not fully described. We aimed here at reproducing and characterizing these clinical signs in a progressive non-human primate model of the Parkinson’s disease to better understand the underlying physiopathology and to identify biomarkers of the disease. Three adult non-human primates (macaca fascicularis) were equipped with a polysomnographic telemetry system allowing the characterization of the wake/sleep behavior by long-term neurophysiological recordings and a modified multiple sleep latency test. Experiments were first performed in healthy animals and then during the progressive induction of a parkinsonian syndrome by chronic intramuscular injections of low doses of MPTP. We observed a significant early onset of wake/sleep behavior disturbances, before any motor symptoms, resulting in (i) a disorganization of nighttime sleep with more deep sleep and (ii) a disorganization of daytime naps with an excessive daytime sleepiness characterized by longer duration of naps, which occurred faster. These observations persisted and worsened in stable symptomatic state. In that latter state, we observed persistent excessive daytime sleepiness and more disorganized nighttime sleep architecture and continuity. Interpolating to the human condition, the present study suggests that nighttime and daytime sleep disorders may appear in early stage of the disease. They could thus be used as biomarkers of the disease for early stratification of patients who are at risk of developing Parkinson’s disease.

Self-reported sleep characteristics associated with dementia among rural-dwelling Chinese older adults: a population-based study

Background Sleep characteristics associated with dementia are poorly defined and whether their associations vary by demographics and APOE genotype among older adults are unclear. Methods This population-based cross-sectional study included 4742 participants (age ≥ 65 years, 57.1% women) living in rural China. Sleep parameters were measured using the self-rated questionnaires of the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE). Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria, and the National Institute on Aging-Alzheimer’s Association criteria for Alzheimer’s disease (AD). Data were analysed using multiple logistic and general linear regression models. Results Dementia was diagnosed in 173 participants (115 with AD). Multivariable-adjusted odds ratio (OR) of dementia was 1.71 (95%CI, 1.07-2.72) for sleep duration ≤4 h/night (vs. > 6-8 h/night), 0.76 (0.49-1.18) for > 4-6 h/night, 1.63 (1.05-2.55) for > 8 h/night, 1.11 (1.03-1.20) for lower sleep efficiency (per 10% decrease), and 1.85 (1.19-2.89) for excessive daytime sleepiness. Very short sleep duration (≤4 h/night), lower sleep efficiency, and excessive daytime sleepiness were significantly associated with being diagnosed with AD (multivariable-adjusted OR range = 1.12-2.07; p < 0.05). The associations of sleep problems with dementia and AD were evident mainly among young-old adults (65-74 years) or APOE ε4 carriers. Among dementia-free participants, these sleep characteristics were significantly associated with a lower MMSE score. Conclusions Self-reported sleep problems in dementia are characterized by very short or long sleep duration, low sleep efficiency, and excessive daytime sleepiness, especially among young-old people and APOE ε4 carriers. Trial registration ChiCTR1800017758 (Aug 13, 2018).

Evaluation Parameter of Excessive Daytime Sleepiness for Obstructive Sleep Apnea Patients

Background and Objective Obstructive sleep apnea (OSA) is a sleep-related breathing disorder caused by repetitive obstruction of the upper airway. Repetitive obstruction of the upper airway causes impaired gaseous exchange, resulting hypoxia, hypercapnia, and frequent arousals of sleep architecture. Polysomnography (PSG) is a gold standard for diagnosing OSA. Excessive daytime sleepiness (EDS) is a common accompanying daytime symptoms in OSA patients. Since EDS can cause unexpected events such as traffic accident or poor performance in workplace, it is regarded as a significant public health problem. Therefore, accurate assessment and prediction of this symptom is important. The Epworth Sleepiness Scale (ESS) and multiple sleep latency test are most commonly used to evaluate EDS, but their efficacies are controversial. The purpose of this study is to find the parameter to evaluate and predict the EDS for OSA patients.Methods We retrospectively reviewed the medical records of 88 OSA patients. Patients were divided into two groups according to the presence of EDS. We analyzed the clinical records, questionnaire scores, and PSG data to find the difference between two groups.Results ESS was 10.64 ± 4.28 in EDS patients and 8.63 ± 4.86 in non-EDS patients. ESS showed a statistically significant difference between two groups (p = 0.044). Also, the percentage of 1st stage non-REM sleep in total sleep time (N1%) was 25.09 ± 15.24 in EDS patients and 18.97 ± 10.30 in non-EDS patients and showed a statistically significant difference between groups (p = 0.033). Patients’ weight was 81.59 ± 20.52 in EDS patients and 74.14 ± 12.63 in non-EDS patients and showed a statistically significant difference between groups (p = 0.046).Conclusions ESS, N1% and patients’ weight were significant parameter which is related with the presence of EDS for OSA patients. These parameters will be useful in evaluating the presence of EDS for OSA patients. Also, in patients diagnosed with sleep disorder with high N1%, EDS must be accurately evaluated as well.

Treatment of narcolepsy: A rare disease of unknown etiology

Background: Narcolepsy, also known as Gélineau syndrome, is a chronic and neurological disease that affects 0.05% of the European population, though that percentage could be higher due to the diagnostic difficulties. The main symptom is excessive daytime sleepiness, although it may be accompanied by cataplexy, sleep paralysis and hypnagogic hallucinations. Objective: Nowadays, there is no cure for narcolepsy and the treatment is symptomatic: psychostimulants for the sleepiness by means of amphetamines, methylphenidate or modafinil, and antidepressants and sodium oxybate for treating cataplexy. Method: This is a short review regarding pharmacotherapy for narcolepsy. Result: Hypocretins were discovered in 1998. They are neuropeptides whose deficit is responsible for this symptomatology, has opened up a new field of investigation. Conclusion: Agonists of hypocretins could be a promising therapy against this disease.

Daytime Hypersomnolence in COVID-19: A Case Report and Literature Review

Coronavirus infectious disease 2019 (COVID-19) is confirmed to develop neurocognitive complications. In the present paper, we describe two patients with laboratory-confirmed COVID-19 and excessive daytime sleepiness. In the present study, we reported two laboratory-confirmed cases of COVID-19 with excessive daytime sleepiness. Patients had drowsiness and mild confusion on presentation. In both cases, CNS infections, including meningitis and encephalitis, were ruled out. Both patients’ symptoms remarkably improved following the therapeutic course indicating the direct effect of SARS-CoV2 in sleep modulating centers on the brain. COVID-19 should be considered in patients with excessive daytime sleepiness and drowsiness in the current outbreak.