Increased Sleep Fragmentation Research Articles

P14: Chronobiological assessment of stable elderly individuals with type I bipolar disorder

Objectives: Evaluate the chronobiological rhythm of elderly people with type I bipolar disorder (BD), stable and without dementia, compared to controls.Methods: A cross-sectional study was performed with 20 patients diagnosed with type I bipolar disorder, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and 20 controls. Actigraphic records were gathered from all participants over 7 days, besides clinical and demographic information. Non-parametric chronobiological measurements were calculated to evaluate the activity-rest cycle. Comparisons between groups were evaluated using Student’s t-test or Mann-Whitney test, for data with normal and non- normal distribution, respectively. All procedures were conducted following the principles outlined in the Declaration of Helsinki.Results: Compared to controls, patients with type I BD exhibited lower M10 values, which represent the average activity during the 10 hours of peak movement within 24 hours. Additionally, they showed increased daytime and nighttime inactivity, decreased exposure to nighttime light, and higher sleep fragmentation, as evaluated by the Hurst exponent. No differences were observed between the groups about L5 values, a parameter that indicates the average activity time in the 5 hours of least activity within 24 hours, exposure to daylight, and autocorrelation, a measure that assesses sleep synchronization.Conclusions: Differences in chronobiological patterns were observed between elderly patients with type I BD and controls. In general, patients exhibited reduced activity levels, both during the daytime and nighttime. These findings may be related to the progression of the disease, as well as prolonged exposure to medications to treat BD, such as mood stabilizers and antipsychotics. The increased sleep fragmentation observed in patients may also be associated with these factors. To date, there is a lack of data assessing the chronobiological rhythm and sleep patterns in elderly individuals with TB, underscoring the need for further studies involving thispopulation.

Sleep disturbance in clinical and preclinical scrapie-infected sheep measured by polysomnography

Neurodegenerative diseases are characterised by neuronal loss and abnormal deposition of pathological proteins in the nervous system. Among the most common neurodegenerative diseases are Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease and transmissible spongiform encephalopathies (TSEs). Sleep and circadian rhythm disturbances are one of the most common symptoms in patients with neurodegenerative diseases. Currently, one of the main objectives in the study of TSEs is to try to establish an early diagnosis, as clinical signs do not appear until the damage to the central nervous system is very advanced, which prevents any therapeutic approach. In this paper, we provide the first description of sleep disturbance caused by classical scrapie in clinical and preclinical sheep using polysomnography compared to healthy controls. Fifteen sheep classified into three groups, clinical, preclinical and negative control, were analysed. The results show a decrease in total sleep time as the disease progresses, with significant changes between control, clinical and pre-clinical animals. The results also show an increase in sleep fragmentation in clinical animals compared to preclinical and control animals. In addition, sheep with clinical scrapie show a total loss of Rapid Eye Movement sleep (REM) and alterations in Non Rapid Eyes Movement sleep (NREM) compared to control sheep, demonstrating more shallow sleep. Although further research is needed, these results suggest that prion diseases also produce sleep disturbances in animals and that polysomnography could be a diagnostic tool of interest in clinical and preclinical cases of prion diseases.

The Swiss Primary Hypersomnolence and Narcolepsy Cohort Study: feasibility of long-term monitoring with Fitbit smartwatches in central disorders of hypersomnolence and extraction of digital biomarkers in narcolepsy.

The Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (SPHYNCS) is a multicenter research initiative to identify new biomarkers in central disorders of hypersomnolence (CDH). Whereas narcolepsy type 1 (NT1) is well characterized, other CDH disorders lack precise biomarkers. In SPHYNCS, we utilized Fitbit smartwatches to monitor physical activity, heart rate, and sleep parameters over 1 year. We examined the feasibility of long-term ambulatory monitoring using the wearable device. We then explored digital biomarkers differentiating patients with NT1 from healthy controls (HC). A total of 115 participants received a Fitbit smartwatch. Using a adherence metric to evaluate the usability of the wearable device, we found an overall adherence rate of 80% over 1 year. We calculated daily physical activity, heart rate, and sleep parameters from 2 weeks of greatest adherence to compare NT1 (n = 20) and HC (n = 9) participants. Compared to controls, NT1 patients demonstrated findings consistent with increased sleep fragmentation, including significantly greater wake-after-sleep onset (p = .007) and awakening index (p = .025), as well as standard deviation of time in bed (p = .044). Moreover, NT1 patients exhibited a significantly shorter REM latency (p = .019), and sleep latency (p = .001), as well as a lower peak heart rate (p = .008), heart rate standard deviation (p = .039) and high-intensity activity (p = .009) compared to HC. This ongoing study demonstrates the feasibility of long-term monitoring with wearable technology in patients with CDH and potentially identifies a digital biomarker profile for NT1. While further validation is needed in larger datasets, these data suggest that long-term wearable technology may play a future role in diagnosing and managing narcolepsy.

Sleep fragmentation affects glymphatic system through the different expression of AQP4 in wild type and 5xFAD mouse models

AbstractBackgroundSleep is an important physiological process, during which extracellular metabolic wastes, such as amyloid and tau protein, are cleared via paravascular pathway. Changes in the timing and structure of sleep occur across the lifespan. Increased sleep fragmentation and reductions in slow wave sleep (SWS) represent the hallmark signs of age‐related changes in sleep. The origin of sleep disturbances in AD is thought to be multifactorial. In the aging brain, the impairment of glymphatic pathway function slows the clearance of interstitial Aβ, rendering the aging brain vulnerable to neurodegenerative disease. Several authors have independently shown that glymphatic flux depends upon the expression and perivascular localization of the astroglial water channel aquaporin‐4 (AQP4).MethodIn this study, we performed and validated a mouse model of AD and chronic sleep fragmentation, a sleep disorder that mimics more correctly a real condition of intermittent and continuous awakening. We analyzed the effect of sleep fragmentation in wild type and 5xFAD mice. All the animals underwent to behavioral studies to analyze anxiety and spatial and working memory. We had validated sleep fragmentation and its effect through EEG and biomolecular analysis, by observing all the macro‐areas implied in sleep regulation.ResultWe noticed that sleep fragmentation induces a general acceleration of AD progression in 5xFAD mice, while in wild type mice it affects cognitive behaviors in particular learning and memory. Both these events may be correlated to AQP4 modulation, a crucial player of the glymphatic system activity. In particular, sleep fragmentation differentially affects AQP4 expression according to the stage of the disease, with an up‐regulation in younger animals, while such change cannot be detected in older ones. Moreover, in wild type mice sleep fragmentation affects cognitive behaviors, in particular learning and memory, by compromising the glymphatic system through the decrease of AQP4.ConclusionNevertheless, an in‐depth study is needed to better understand the mechanism by which AQP4 is modulated and whether it could be considered a risk factor for the disease development in wild type mice. If our hypotheses are going to be confirmed, AQP4 modulation may represent the convergence point between AD and sleep disorder pathogenic mechanisms

Abstract 18921: Obstructive Sleep Apnea in the Presence of Heart Failure With Preserved Ejection Fraction is Associated With Low Arousal Threshold and Increased Sleep Fragmentation

Introduction: Heart failure with preserved ejection fraction (HFpEF) is often accompanied by obstructive sleep apnea (OSA). The effects of HFpEF on OSA pathophysiology remain relatively unexplored. Pulmonary congestion and sympathetic nervous activity (SNA) may drive ventilatory control instability (high loop gain [LG]). Elevated SNA also theoretically predisposes sleep to easier interruption by breathing events of OSA, reflected by low arousal threshold (ArTH). Hypothesis: In comparison to patients with OSA alone, patients with both OSA and HFpEF have higher LG and lower ArTH. Methods: We reviewed records to include patients with 1) transthoracic echocardiography with EF>40% and left ventricular diastolic dysfunction by decreased age-adjusted e’ and/or left atrial volume index >28 mL/m 2 ; 2) OSA by apnea-hypopnea index (AHI3A) ≥15 events/hour; and 3) raw polysomnography (PSG) data available for advanced signal analysis. LG and ArTH were estimated by Phenotyping Using Polysomnography (PUP), a MATLAB algorithm that quantifies pathophysiologic mechanisms of OSA using PSG data. Values in HFpEF+OSA patients were compared to values from research volunteers with OSA alone. Results: The HFpEF+OSA group included 21 patients. The OSA alone group included 43 research volunteers. LG was lower for HFpEF+OSA (0.63±18) compared to OSA alone (0.69±18), but the difference was not statistically significant. ArTH was significantly lower for HFpEF+OSA (117.0±15.9 %eupnea) compared to OSA alone (152.8±54.8 %eupnea, p = <0.001) and remained significant after adjustment for age, sex, and body mass index. ArTH was correlated with sleep efficiency (R = 0.43, p = <0.001) and negatively correlated with wake after sleep onset (R = -0.35, p =0.005). Conclusions: HFpEF is associated with low arousal threshold, which may contribute to sleep fragmentation. Our data did not confirm the hypothesis of greater breathing instability in patients with HFpEF and OSA compared to OSA alone.

0097 Sleep and Eating Rhythms are Associated with Metabolic Risk in Postmenopausal Women

Abstract Introduction Postmenopausal women are particularly vulnerable to metabolic dysfunction. Compelling evidence suggests that this is due to their lacking the protective effect of estrogens. We have shown that circulating estrogens regulate daily eating and sleep-activity rhythms in female mice and protect them from obesity and diabetes. However, few studies have investigated whether postmenopausal women have disrupted eating and sleep-activity rhythms that could contribute to their metabolic dysfunction. The purpose of this study was to investigate the relationship between eating rhythms, sleep, and metabolic risk in postmenopausal women. Methods During 7 days, we studied sedentary, postmenopausal women who were not taking hormones (estrogens ± progestin) and were metabolically unhealthy, defined as prediabetic or normal glucose tolerance with at least 1 feature of the metabolic syndrome. Women taking medications affecting sleep or eating were excluded. Sleep timing and quality were assessed by actigraphy and sleep logs. Times of first and last meals were collected from participants with a texting system. Body composition (DXA), body mass index (BMI), and waist circumference were collected as markers of obesity. Lipid metabolism and glycemic control were assessed by fasting lipid panel and HbA1c as well as oral glucose tolerance test. Results Eighteen postmenopausal women (mean ± SEM; 57.2 ± 1.1 years) participated in the study. Both sleep timing and quality were associated with metabolic risk in postmenopausal women. Specifically, later timing of sleep onset was associated with later meal timing and greater BMI and body fat percentage. Increased sleep fragmentation was associated with reduced HDL. In addition, both the timing and duration of eating were associated with worse metabolic measures. Longer eating duration was associated with larger waist circumference. Later eating time was associated with greater waist circumference and BMI. Conclusion We found that late timing and poor quality of sleep, as well as long eating duration, are associated with markers of metabolic risk in postmenopausal women. These data suggest that interventions that reduce eating duration and advance the timing of last meal and sleep onset may improve metabolic risk in postmenopausal women. Support (if any) This study is supported by NIH awards R01DK124774, T32 AG078110, and UL1TR001998.

Somatostatin neuron contributions to cortical slow wave dysfunction in adult mice exposed to developmental ethanol.

Transitions between sleep and waking and sleep-dependent cortical oscillations are heavily dependent on GABAergic neurons. Importantly, GABAergic neurons are especially sensitive to developmental ethanol exposure, suggesting a potential unique vulnerability of sleep circuits to early ethanol. In fact, developmental ethanol exposure can produce long-lasting impairments in sleep, including increased sleep fragmentation and decreased delta wave amplitude. Here, we assessed the efficacy of optogenetic manipulations of somatostatin (SST) GABAergic neurons in the neocortex of adult mice exposed to saline or ethanol on P7, to modulate cortical slow-wave physiology. SST-cre × Ai32 mice, which selectively express channel rhodopsin in SST neurons, were exposed to ethanol or saline on P7. This line expressed similar developmental ethanol induced loss of SST cortical neurons and sleep impairments as C57BL/6By mice. As adults, optical fibers were implanted targeting the prefrontal cortex (PFC) and telemetry electrodes were implanted in the neocortex to monitor slow-wave activity and sleep-wake states. Optical stimulation of PFC SST neurons evoked slow-wave potentials and long-latency single-unit excitation in saline treated mice but not in ethanol mice. Closed-loop optogenetic stimulation of PFC SST neuron activation on spontaneous slow-waves enhanced cortical delta oscillations, and this manipulation was more effective in saline mice than P7 ethanol mice. Together, these results suggest that SST cortical neurons may contribute to slow-wave impairment after developmental ethanol.

Polysomnographic Assessment of Effects of Tobacco Smoking and Alcohol Consumption on Sleep Bruxism Intensity.

Background: Sleep bruxism (SB) is a common sleep-related movement behavior with a complex etiology. A recent hypothesis suggests psychoactive substance usage, tobacco smoking, and alcohol intake are risk factors for SB. This study aimed to evaluate SB intensity in tobacco smokers and alcohol drinkers. Methods: A total of 133 adults underwent full-night audio- and video-polysomnography, and the polysomnograms were evaluated using the American Academy of Sleep Medicine guidelines. The study group was divided into smoker and nonsmoker groups as well as drinker and non-drinker groups. Results: The results of the polysomnographic analysis confirmed that tobacco smoking has a significant effects on SB. Tobacco smokers showed increased bruxism intensity (5.50 ± 4.71 vs. 3.83 ± 3.26, p < 0.05), especially the mixed phenotype (0.93 ± 1.00 vs. 0.59 ± 0.59, p < 0.05), in the N1 sleep stage (22.84 ± 20.45 vs. 15.66 ± 13.60, p < 0.05) and the nonsupine position (4.93 ± 5.56 vs. 2.50 ± 2.31, p < 0.05). They also showed a higher number of bruxism episodes with arousal compared with nonsmokers (2.91 ± 2.83 vs. 1.61 ± 1.49, p < 0.05), indicating increased sleep fragmentation. However, no significant effect of alcohol on SB intensity was observed, and the bruxism episode index was similar in alcohol drinkers and nondrinkers. In addition, electrolyte disturbances and lipid disorders were evaluated. Compared with nonsmokers, tobacco smokers showed a higher concentration of plasma triglycerides (177.67 ± 106.9 vs. 129.18 ± 65.61) and lower levels of iron and magnesium (96.68 ± 43.58 vs. 123.83 ± 52.36 and 1.85 ± 0.22 vs. 1.96 ± 0.21, respectively). Conclusions: In summary, this study showed that tobacco smoking, but not alcohol consumption, is related to bruxism intensity and lipid and electrolyte disturbances in individuals with sleep disorders.

Age estimation from sleep studies using deep learning predicts life expectancy

Sleep disturbances increase with age and are predictors of mortality. Here, we present deep neural networks that estimate age and mortality risk through polysomnograms (PSGs). Aging was modeled using 2500 PSGs and tested in 10,699 PSGs from men and women in seven different cohorts aged between 20 and 90. Ages were estimated with a mean absolute error of 5.8 ± 1.6 years, while basic sleep scoring measures had an error of 14.9 ± 6.29 years. After controlling for demographics, sleep, and health covariates, each 10-year increment in age estimate error (AEE) was associated with increased all-cause mortality rate of 29% (95% confidence interval: 20–39%). An increase from −10 to +10 years in AEE translates to an estimated decreased life expectancy of 8.7 years (95% confidence interval: 6.1–11.4 years). Greater AEE was mostly reflected in increased sleep fragmentation, suggesting this is an important biomarker of future health independent of sleep apnea.

0319 Age Estimation from Sleep using Deep Learning Predicts Life Expectancy

Abstract Introduction Sleep disturbances increase with age and are predictors of mortality. However, summary metrics typically derived in sleep clinics from gold standard clinical analysis of polysomnograms (PSGs) only represent a very small fraction of data collected. In this study, we designed deep neural networks that estimate age as a proxy for overall health using full PSG signals. Age estimation was next used to evaluate association to mortality risk. Methods Aging was modeled using 2,500 PSGs and tested in 10,808 PSGs from men and women in 7 different cohorts aged between 20 and 90. The deep neural network was trained using as a regression model of age in the 2,500 PSGs roughly uniformly distributed across 6 to 90 years. The estimates of the network were interpreted using Gradient SHAP, which attributes relevance scores to the input in terms of the age estimate. The association between age estimate error (AEE), which is the residual of the estimate, and mortality risk was investigated with Cox proportional hazards models that adjusted for demographics, sleep, and health covariates. Results Ages were estimated with a mean absolute error of 5.81 ± 1.18 years, while a linear regression model using basic sleep scoring measures had an error of 15.10 ± 6.48 years. Interpretation of the network revealed that patterns such as arousal, sleep apnea, and sleep stage transitions contribute to the age estimate. Each 10-year increment in AEE was associated with increased all-cause mortality rate of 28 % (95% confidence interval: 19–38 %) and cardiovascular mortality rate of 38 % (95% confidence interval: 19 – 59 %). An increase from -10 to +10 years in AEE translates to an estimated decreased life expectancy of 6.21 years (95% confidence interval: 4.31–8.21 years). Conclusion Greater AEE was mostly reflected in increased sleep fragmentation, suggesting this is an important biomarker of future health independent of sleep apnea. Support (If Any) The Klarman Family Foundation and grants HL46380, M01 RR00080-39, T32-HL07567, RO1-46380, U01HL53916, U01HL53931, U01HL53934, U01HL53937, U01HL64360, U01HL53938, U01HL53940, U01HL53941, U01HL63463, 38-PM-07, R01HL62252, R01AG036838, R01AG058680, 1UL1RR025011, U01AG027810, U01AG042124, U01AG042139, U01AG042140, U01AG042143, U01AG042145, U01AG042168, U01AR066160, UL1TR000128, R01HL071194, R01HL070848, R01HL070847, R01HL070842, R01HL070841, R01HL070837, R01HL070838, R01HL070839, R24HL114473, and 75N92019R002.

0132 Loss of Neurons in the Intermediate Nucleus is Related to Perturbed Sleep-Wake Rhythms in Older Adults

Abstract Introduction The ventrolateral preoptic nucleus (VLPO) is composed of neurons that are maximally active during sleep. In animal studies, VLPO lesion decreased the amount of sleep but only marginally attenuated circadian rhythm. The human intermediate nucleus (IN) is believed to be the homologue of the VLPO. Neuronal loss in IN has found to be associated with increased sleep fragmentation in older adults. We investigated whether IN neuronal loss is also associated with perturbed sleep-wake rhythms in humans. Methods We studied 50 deceased participants [age at death: 88.9±6.1 (mean±SD; female: 33 (66%)] from the Rush Memory and Aging Project, who had actigraphy assessment 1.6±1.3 years (range: 0.1-5.1 years) before death. Post-mortem immunohistochemical and stereological analysis was performed to quantify the count of galanin-immunoreactive neurons (Gal+) in the IN of them. Actigraphy data were used to calculate amplitude, acrophase, interdaily stability, and intradaily variability of the 24-h activity rhythms. Linear regression models were used to determine the associations of the four measures of sleep-wake rhythms with the GAL+ neuron counts, adjusting for age at death and sex. Further covariates considered included sleep fragmentation (derived from actigraphy) and the time interval between actigraphy assessment and death. Results The number of Gal+ neurons in IN was positively associated with interdaily stability and amplitude, and negatively associated with intradaily variability. Specifically, for one-SD decrease in Gal+ neurons, interdaily stability decreased by 0.06±0.02 (mean±standard error; equivalent to 40% SD of interdaily stability; p=0.009), amplitude decreased by 5.8±2.3 (equivalent to 35% SD of amplitude; p=0.014), and intradaily variability increased by 0.12±0.04 (equivalent to 36% SD of intradaily variability; p=0.009). Longer time interval between actigraphy and death showed a trend to attenuate these associations although not statistically significant (all p&amp;gt;0.1). These observations also remained statistically significant after adjusting for sleep fragmentation. Conclusion Neuronal loss in the IN was linked with perturbed sleep-wake rhythms in older adults. Further investigations are warranted to examine whether the observed associations are mediated by reduced sleep quantity or other aspects of sleep quality. Support (If Any) NIH RF1AG064312, RF1AG059867, R01AG017917, R01AG56352; and the BrightFocus Foundation A2020886S.

Sleep in children with refractory epilepsy and epileptic encephalopathies: A systematic review of literature.

Children with epilepsy have more sleep disorders compared to healthy children. The bidirectional interaction between epilepsy and sleep is not completely understood. However, disruption of sleep architecture during childhood may have consequences for cognitive development. As children with drug-refractory epilepsy often have intellectual disability, sleep disruption could be an important contributing factor in severity of their cognitive impairment. To better understand these interactions, sleep architecture in children with drug-refractory epilepsy and epileptic encephalopathies should be investigated. In this review, we conducted a systematic literature search on this topic. Articles that investigated sleep macro- and/or microstructure by means of electroencephalogram/polysomnography were included, as well as articles that used validated questionnaires. Sixteen articles were reviewed, eight of which used polysomnography. Only 2 articles examined sleep in children with epileptic encephalopathies. Consistent findings on measures of sleep architecture were a reduction in REM percentage and an increase in sleep fragmentation when comparing drug-refractory patients with non-refractory and healthy subjects. The findings on slow wave sleep were less clear. Studies with questionnaires unambiguously confirmed subjectively more sleep problems in children with drug-refractory epilepsy. This is the first review of literature in this patient population. More good quality sleep studies in children with drug-refractory epilepsy are warranted. The use of wearables in the home setting together with automatic sleep staging could provide more insights.

Objectively-measured sleep patterns and cardiometabolic health in a rural South African setting: a cross sectional analysis

BackgroundTo investigate the relationship between objectively-measured, free-living sleep patterns, and cardiometabolic health, in a rural South African health and demographic surveillance site.MethodsWrist-mounted actigraphy data was collected over nine days from 167 adults (≥ 40 years). Sleep patterns were constructed from tertiles of sleep quantity and quality parameters (TST: total sleep time, AC: activity counts during sleep) from valid minute-by-minute data. The reference category was Moderate TST/Low-to-Moderate AC. Self-reported data included behavioural, health and socio-demographic variables. Biological data included anthropometry, resting blood pressure and fasting blood glucose, insulin and lipids. Binary and ordinal logistic regression models were constructed to determine the association between TST and AC, the factors associated with sleeping patterns, and the association between sleeping patterns and Insulin resistance (HOMA-IR) and Metabolic Syndrome (MetS). HOMA-IR and MetS were also examined across sleep patterns using analysis of variance models.ResultsA total of 139 adults (71.2% female) had a complete dataset. In unadjusted analyses, females had poorer sleep quality, were more physically active, and displayed poorer cardiometabolc health and greater adiposity than males (p ≤ 0.017). There were no sex differences in TST or sleep pattern distribution (p ≤ 0.901). Not being classified as Low TST/High AC or exposed to ≥ 1 bout of Low TST/High AC sleep was associated with lower physical activity, longer sleep duration, better sleep quality and lower IR (p ≤ 0.0452). In multivariate analyses, there was no association between TST and AC (p = 0.921), while increasing age and people-to-bedroom density, and lower physical activity where significantly associated with increasing TST (p ≤ 0.027). Participants classified as Low TST/High AC had significantly higher HOMA-IR, but not MetS, compared with Moderate TST/Low AC (p = 0.021). Being exposed to ≥ 1 bout of Low TST/High AC sleep was significantly associated with hypertension (OR = 2.31, 95%CI: 1.00, 5.34), but not for HOMA-IR or MetS (p ≥ 0.227).ConclusionsLong sleep was not associated with increased sleep fragmentation. Short, fragmented sleep was associated with insulin resistance. Exposure to at least one bout of short, fragmented sleep increased the likelihood of hypertension. Further studies are required to identify the factors associated with short, fragmented sleep in this setting.

The effects of napping on night-time sleep in healthy young adults.

The discrepancies in the effects of napping on sleep quality may be due to differences in methodologies, napping behaviours, and daytime activity levels across studies. We determined whether napping behaviours and daytime activity levels are associated with night-time sleep fragmentation and sleep quality in young adults. A total of 62 healthy adults (mean [SD] age 23.5[4.2]years) completed screening questionnaires for sleep habits, physical activity, medical and psychological history. Actigraphy was used to record sleep including naps. The fragmentation algorithm (KRA ) was applied to the actigraphic data to measure night-time sleep fragmentation. We classified participants' nap frequency as "non-nappers" (0naps/8days), "moderate nappers" (1-2naps/8days) or "frequent nappers" (≥3naps/8days) naps. Nap duration was defined as "short" (≤60min) or "long" (>60min). Naps' proximity to the night sleep episode was defined as "early" (≥7h) and "late" (<7h) naps. Outcome variables were night-time KRA and actigraphic sleep variables. Frequent nappers had a significantly higher KRA than moderate nappers (p<0.01) and non-nappers (p<0.02). Late naps were associated with poorer measures of night sleep quality versus early naps (all p≤0.02). Nap duration and daytime activity were not associated with significant differences in the outcome variables (all p>0.05). KRA correlated with sleep duration, sleep efficiency, and awakenings (r=-0.32, -0.32, and 0.53, respectively; all p<0.05). Frequent napping and late naps may be associated with increased sleep fragmentation and poorer sleep quality, reflected in longer sleep onsets and increased awakenings. These findings have implications for public health sleep hygiene recommendations.

Sleep architecture in patients with interstitial lung disease with and without pulmonary hypertension

Sleep disturbance is common in patients with advanced interstitial lung disease (ILD) often complicated by pulmonary hypertension (PH) and may contribute to poor quality of life. The etiology of sleep disturbance and the relationship between PH and sleep architecture in patients with ILD remains unknown. We performed a retrospective cohort study comparing sleep architecture on polysomnography in patients with ILD with and without PH, defined as mean pulmonary artery pressure on right heart catheterization ≥ 20mmHg. We tested the hypothesis that patients with ILD and PH would have increased wake time after sleep onset (WASO) compared to patients with ILD without PH using univariate analysis and multivariable linear regression. In our cohort of patients with ILD who underwent polysomnography (N = 49), patients with PH had lower total diffusion capacity for carbon monoxide (DLCO) (9.28 vs. 12.87ml/min/mmHg, P = 0.04) and percent DLCO (39% vs. 53%, P = 0.03). On polysomnography, patients with PH had increased percentage of total sleep time with saturation < 90% (T90) (17% vs. 6%, P = 0.03), decreased N2 sleep (181 vs. 233min, P = 0.03), decreased %N2 sleep (59% vs. 66%, P = 0.04), increased %N1 sleep (22% vs. 14%, P = 0.02), decreased sleep efficiency (62% vs. 72%, P = 0.03), and increased WASO (133 vs. 84min, P = 0.01). In multivariable analysis, PH was associated with a 43-min increase in WASO (95% CI 6.2-80.2, P = 0.02). Patients with ILD and PH have decreased total and %N2 sleep, increased %N1 sleep, decreased sleep efficiency, and increased WASO, likely indicating increased sleep fragmentation.

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.

Sleep breathing disorders in pediatric patients with spinal muscular atrophy 2

ObjectivesThe study is aimed to analyze both sleep architecture and prevalence of sleep-disordered breathing (SDB), in a group of patients with type 2 spinal muscular atrophy (SMA), considering motor dysfunction, and compare them with age-matched controls. MethodsEighteen SMA type 2 patients (nine males median age 9.5 (4–17) years) and eighteen controls (fourteen males, median age 8,5 (1–16) years) underwent nocturnal polysomnography. SMA type 2 patients were evaluated with motor scales; Hammersmith Functional Motor Scale Expanded (HFMSE), Revised upper limb model (ULMR) and Egen Klassification Scale Version 2 (EK2). Parents/tutors completed two pediatric sleep questionnaires (respiratory subscale from Chervin Pediatric Sleep Questionnaire and Bruni's Sleep Disturbance Scale for Children). ResultsWhen compared with controls, SMA type 2 patients showed no significant differences in age (9.72 ± 4.2 vs 8.22 ± 3.9 (p = 0.28), gender 9 (9 men (50%) vs 14 (77,8%) (p = 0.083) and nutritional status; Body Mass Index (BMI) (16.4 (12.2–34.8) vs 17.6 (4.4–24.2) (p = 0.83). Apnea Hypopnea Index (AHI) was statistically higher in SMA type 2 patients (6.7 ± 6.2 vs 0.4 ± 0.3) (p < 0.001). The SpO2 mean values in cases were (96% ± 1.4) vs (97.5% ± 1.2) (p = 0.007). TcPCO2 median value (41,5 mmHg; (range 34–47.2) in the SMA type-2 patients within normal reference values. Only one motor scale; Hammersmith Functional Motor Scale Expanded (HFMSE) showed a negative correlation with AHI (r = −0.132). ConclusionsPatients affected by SMA type 2 presented significantly higher apnea-hypopnea indices than controls; differences in sleep architecture identified include: decreased total sleep time, increased percentage of stage N1 of NREM sleep as well as increased sleep fragmentation seen in the SMA type 2 group, due to respiratory related arousals. We would like to point out that validated pediatric sleep questionnaires in general population, may not be useful tools when screening for SDB in these patients. This should be taken into consideration in clinical practice and in the elaboration of future clinical guidelines for these patients.

Short-term maintenance on a high-sucrose diet alleviates aging-induced sleep fragmentation in drosophila

ABSTRACT Sleep is a fundamental behavior in an animal’s life influenced by many internal and external factors, such as aging and diet. Critically, poor sleep quality places people at risk of serious medical conditions. Because aging impairs quality of sleep, measures to improve sleep quality for elderly people are needed. Given that diet can influence many aspects of sleep, we investigated whether a high-sucrose diet (HSD) affected aging-induced sleep fragmentation using the fruit fly, Drosophila melanogaster. Drosophila is a valuable model for studying sleep due to its genetic tractability and many similarities with mammalian sleep. Total sleep duration, sleep bout numbers (SBN), and average sleep bout length (ABL) were compared between young and old flies on a normal sucrose diet (NSD) or HSD. On the NSD, old flies slept slightly more and showed increased SBN and reduced ABL, indicating increased sleep fragmentation. Short-term maintenance of flies in HSD (up to 8 days), but not long-term maintenance (up to 35 days), suppressed aging-induced sleep fragmentation. Our study provides meaningful strategies for preventing the deterioration of sleep quality in the elderly.

EEG Patterns Prior to Motor Activations of Parasomnias: A Systematic Review.

IntroductionNon-rapid eye movement (NREM) parasomnias are defined as abnormal nocturnal behaviors that typically arise from the NREM sleep stage 3 during the first sleep cycle. The polysomnographic studies showed an increase in sleep fragmentation and an atypical slow wave activity (SWA) in participants with NREM parasomnias compared to healthy controls. To date, the pathophysiology of NREM parasomnias is still poorly understood. The recent investigation of the EEG patterns immediately before parasomnia events could shed light on the motor activations’ processes. This systematic review aims to summarize empirical evidence about these studies and provide an overview of the methodological issues.MethodsA systematic literature search was carried out in PubMed, Web of Science, and Scopus, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The documents obtained were evaluated using the Newcastle–Ottawa Scale (NOS).ResultsNine studies were included in the qualitative synthesis. The major evidence revealed an increased slow frequency EEG activity immediately before the motor activations in frontal and central areas and increased beta activity in the anterior cingulate cortices.DiscussionThe investigation of EEG patterns before parasomniac episodes could provide new insight into the study of NREM parasomnia pathophysiology. The high- and low-frequency EEG increase before the episodes could represent a predictive electrophysiological pattern of the motor activations’ onset. Overall, identifying specific sleep markers before parasomnias might also help differentiate between NREM parasomnias and other motor sleep disorders. Different methodological protocols should be integrated for overcoming the lack of consistent empirical findings. Thus, future studies should focus on the topographical examination of canonical EEG frequency bands to better understand spatial and time dynamics before the episodes and identify the networks underlying the onset of activations.

Objectively measured sleep fragmentation is associated with incident delirium in older hospitalized patients: Analysis of data collected from an randomized controlled trial.

Delirium may lead to poor outcomes in hospitalized older adults, and sleep deprivation may contribute to its pathogenesis. Thus, we sought to measure sleep duration and fragmentation using wrist-worn actigraphy in older, hospitalized patients with and without delirium, and to determine if actigraphy-based parameters could be used to predict delirium prior to clinical recognition. We conducted a secondary analysis of data from a recent, randomized clinical trial aimed at preventing inpatient delirium. Participants (n=70) were aged≥65 years admitted to an internal medicine service. Delirium was defined by the Confusion Assessment Method, or altered mental status identified by a clinician. Sleep measurements were actigraphy-based, and included total sleep time, median sleep bout duration and other measures of sleep fragmentation. We found that total sleep duration was similar between patients with (n=17) and without (n=53) delirium (mean 384.9±SD 162.7 versus mean 456.6±SD 135.8min; p=.081). Mean sleep bout times were shorter in delirious versus never-delirious patients (median 6.1 [interquartile range 4.3-8.9] versus 7.9 [interquartile range 5.7-11.3] min, p=.048). Patients with delirium had more short sleep bouts (< 10min) and fewer longer sleep bouts (> 30min) compared with those without delirium. Increased sleep fragmentation was present prior to the clinical recognition of delirium. Overall, delirium was associated with increased sleep fragmentation detected by actigraphy, and sleep fragmentation might be useful as a biomarker for delirium prediction in the future.