Association Between Arousals During Sleep and Hypertension Among Patients With Obstructive Sleep Apnea

Background Sleep fragmentation induced by repetitive arousals is a hallmark of obstructive sleep apnea (OSA). Sleep fragmentation has been linked to hypertension in community‐based studies, but it is unclear if this association is manifest in OSA. We aimed to explore whether frequent arousals from sleep modify the relationship between OSA and prevalent hypertension. Methods and Results A total of 10 102 patients with OSA and 1614 primary snorers were included in the study. Hypertension was defined on either direct blood pressure measures or diagnosis by a physician. Spontaneous, respiratory, and movement arousals were derived by polysomnography. Logistic regression models were used to estimate the associations between arousals and prevalent hypertension in patients with OSA and primary snorers. For every 10‐unit increase of total arousal index, odds of hypertension significantly increased in both the total sample (odds ratio [OR], 1.08; 95% CI, 1.03–1.14; P =0.002) and patients with OSA (OR, 1.10; 95% CI, 1.04–1.16; P <0.001), but not in the primary snoring group. Total arousal index was significantly associated with systolic blood pressure and diastolic blood pressure in the total sample (β=0.05 and β=0.06; P <0.001) and in patients with (β=0.05 and β=0.06; P <0.01), but not in primary snorers. In addition, a greater influence of respiratory events with arousals than respiratory events without arousals on blood pressure in OSA was also noted. Results were independent of confounders, including apnea‐hypopnea index and nocturnal hypoxemia. Conclusions We conclude that repetitive arousals from sleep are independently associated with prevalent hypertension in patients with OSA.

Extreme sleep fragmentation for 11 consecutive days and nights does not significantly alter total sleep time, and sleep stage distribution, during the continuous alpine downhill skiing world record

Introduction: Extreme levels of sleep deprivation, fragmentation and management, are major problems in many sportive disciplines, ultramarathons, polar or extreme altitude expeditions, and in space operations. Material and methods: Polysomnographic (PSG) data was continuously recorded (total sleep time and sleep stage distribution) in a 34-year-old male whilst performing the new world record in long-term downhill skiing. He napped only during the short ski lift rides for 11 days and nights. Results: After an initial period of complete sleep deprivation for 24 hours, total sleep time and the total times of non-REM and REM achieved during the lift rides returned to standard values on the second day. PSG data revealed an average sleep time per 24 hours of 6 hours and 6 minutes. During daylight sleep was rarely registered. The subject experienced only two minor falls without injury and immediately resumed skiing. Conclusion: In a healthy, trained, elite male athlete, sleep fragmentation over 11 consecutive days did not significantly impair the sleep, motor or cognitive skills required to perform a continuous downhill skiing world record after an initial adaptation phase.

Does Chronic Sleep Fragmentation Lead to Alzheimer's Disease in Young Wild-Type Mice?

Chronic sleep insufficiency is becoming a common issue in the young population nowadays, mostly due to life habits and work stress. Studies in animal models of neurological diseases reported that it would accelerate neurodegeneration progression and exacerbate interstitial metabolic waste accumulation in the brain. In this paper, we study whether chronic sleep insufficiency leads to neurodegenerative diseases in young wild-type animals without a genetic pre-disposition. To this aim, we modeled chronic sleep fragmentation (SF) in young wild-type mice. We detected pathological hyperphosphorylated-tau (Ser396/Tau5) and gliosis in the SF hippocampus. 18F-labeled fluorodeoxyglucose positron emission tomography scan (18F-FDG-PET) further revealed a significant increase in brain glucose metabolism, especially in the hypothalamus, hippocampus and amygdala. Hippocampal RNAseq indicated that immunological and inflammatory pathways were significantly altered in 1.5-month SF mice. More interestingly, differential expression gene lists from stress mouse models showed differential expression patterns between 1.5-month SF and control mice, while Alzheimer's disease, normal aging, and APOEε4 mutation mouse models did not exhibit any significant pattern. In summary, 1.5-month sleep fragmentation could generate AD-like pathological changes including tauopathy and gliosis, mainly linked to stress, as the incremented glucose metabolism observed with PET imaging suggested. Further investigation will show whether SF could eventually lead to chronic neurodegeneration if the stress condition is prolonged in time.

Objective Sleep Quality and the Underlying Functional Neural Correlates Among Older Adults With Probable MCI

Poor sleep is a strong risk factor for dementia and is commonly reported among older adults with mild cognitive impairment (MCI). However, the neural underpinnings of poor sleep among older adults with MCI remains equivocal. The goal of this cross-sectional analysis was to explore the relationship between resting-state functional connectivity in the brain and sleep quality as measured by actigraphy. We hypothesize lower sleep efficiency and higher sleep fragmentation may be associated with aberrant functional connectivity of brain regions involved in somatosensory, somatomotor, and attentional processing. Thirty-six community-dwelling older adults with probable MCI between 65-85 years (mean=71.8 years) were assessed for sleep quality using a motion watch to quantify sleep efficiency and fragmentation over 14 days. All participants completed resting-state functional magnetic resonance imaging (fMRI) within 14 days of sleep monitoring. Independent associations between network connectivity and sleep quality were determined using general linear models. Examined networks included the somatosensory network (SMN), dorsal attention network (DAN), ventral attention network (VAN), frontoparietal network (FPN), and default mode network (DMN). Mean Montreal Cognitive Assessment score was 22.5 (SD=2.7) and Mini-Mental State Examination score was 28.3 (SD=1.5). Mean sleep efficiency and fragmentation index was 80.1% and 31.8 respectively. Higher sleep fragmentation correlated with increased connectivity between the SMN and insula, the SMN and posterior cingulate, as well as FPN and primary motor area (Z=3.1; p&lt;0.05). These results suggest aberrant functional connectivity between brain regions involved in attentional and somatosensory processes may be associated with disrupted sleep mechanisms in older adults with MCI.

Loneliness, Sleep Quality, and Cognitive Function in Community-Dwelling Older Adults

Loneliness is a risk factor for cognitive decline in older adults, however, the underlying mechanisms are less understood. Individuals who experience frequent loneliness tend to have poorer sleep quality. Empirical evidence supports the influence of sleep on cognitive health. This study examined the possible mediating effect of sleep characteristics on the relationship between loneliness and cognition. The study sample included 557 participants from wave 2 of the National Social Life, Health, and Aging Project who had actigraphy sleep measures (mean age = 73.17, 52.6% female). Loneliness was assessed with the 3-item UCLA Loneliness Scale. Cognitive function was measured with the Montreal Cognitive Assessment. Five sleep quality indicators were objectively recorded with wearable devices: assumed sleep time; actigraphy sleep time; time spent awake after sleep onset (WASO); sleep fragmentation; and sleep percentage (actigraphy sleep/(assumed sleep + WASO)). Path analysis model results show that WASO, fragmentation, and sleep percentage mediate the link between loneliness and cognitive function. Loneliness was positively related to WASO, and WASO was negatively associated with cognition. Loneliness correlated with increased sleep fragmentation which was associated with worse cognitive function. Individuals who had more frequent loneliness had a lower sleep percentage, and sleep percentage was positively associated with cognitive function. Nonetheless, the path from loneliness to these three sleep characteristics became insignificant after controlling for depressive symposiums. Depressive symptoms and fragmentation were found to double mediate the association between loneliness and cognitive function. Sleep and depression could be underlying pathways for the association between loneliness and cognition.

Differential Effect of Light and Dark Period Sleep Fragmentation on Composition of Gut Microbiome and Inflammation in Mice

Bi-directional interactions amongst the gut microbiota, immune system, and brain function are thought to be critical mediators of health and disease. The role sleep plays in mediating these interactions is not known. We assessed the effects of sleep fragmentation (SF) on the microbiota–gut–brain axis. Male C57BL/6NCrl mice (4 to 5 per cage, fed standard lab chow) experienced SF via mechanical stimulation at 2 min intervals during the light (SF) and dark (DD, dark disturbances) periods. Home cage (HC) controls were undisturbed. After 10 days, fecal samples were collected at light onset, midday, light offset, and midnight. Samples were also collected after 10 days without SF. Subsequently, the mice were randomized across groups and allowed 20 additional days of recovery followed by 10 days of SF or DD. To assess effects on the microbiota, 16S rRNA sequencing was used, and mesenteric lymph nodes (MLNs) and cortex and medial prefrontal cortex were analyzed using cytokine arrays. SF and DD produced significant alterations in the microbiota compared to HC, and DD had greater impact than SF on some organisms. SF produced marked suppression in MLNs of chemokines that regulate inflammation (CCL3, CCL4 and their receptor CCR5) and maintain the immune mucosal barrier (Cxcl13) at the same time that cortical cytokines (IL-33) indicated neuroinflammation. DD effects on immune responses were similar to HC. These data suggest that SF alters the microbiome and suppresses mucosal immunity at the same time that mediators of brain inflammation are upregulated. The translational implications for potential application to clinical care are compelling.

Effects of Chronic Intermittent Hypoxia and Chronic Sleep Fragmentation on Gut Microbiome, Serum Metabolome, Liver and Adipose Tissue Morphology

Chronic intermittent hypoxia (CIH) and chronic sleep fragmentation (CSF) are two cardinal pathological features of obstructive sleep apnea (OSA). Dietary obesity is a crucial risk intermediator for OSA and metabolic disorders. Gut microbiota affect hepatic and adipose tissue morphology under conditions of CIH or CSF through downstream metabolites. However, the exact relationship is unclear. Herein, chow and high-fat diet (HFD)-fed mice were subjected to CIH or CSF for 10 weeks each and compared to normoxia (NM) or normal sleep (NS) controls. 16S rRNA amplicon sequencing, untargeted liquid chromatography-tandem mass spectrometry, and histological assessment of liver and adipose tissues were used to investigate the correlations between the microbiome, metabolome, and lipid metabolism under CIH or CSF condition. Our results demonstrated that CIH and CSF regulate the abundance of intestinal microbes (such as Akkermansia mucinphila, Clostridium spp., Lactococcus spp., and Bifidobacterium spp.) and functional metabolites, such as tryptophan, free fatty acids, branched amino acids, and bile acids, which influence adipose tissue and hepatic lipid metabolism, and the level of lipid deposition in tissues and peripheral blood. In conclusion, CIH and CSF adversely affect fecal microbiota composition and function, and host metabolism; these findings provide new insight into the independent and synergistic effects of CIH, CSF, and HFD on lipid disorders.