Women experience more sleep disruptions than men, particularly during hormonal transitions such as puberty, pregnancy, and menopause. This study investigated the role of estradiol (E2) in regulating sleep-wake behavior in female rats and identified the brain regions involved. Using an exogenous E2 replacement model in ovariectomized rats, we assessed changes in sleep-wake patterns via electroencephalographic/electromyogram telemetry. The effects of E2 and progesterone, selective estrogen receptor agonists, and direct brain infusions of E2 and receptor antagonists were evaluated. E2 administration increased wakefulness, reduced non-rapid eye movement (NREM) and rapid eye movement sleep, and decreased NREM slow-wave activity (SWA), predominantly during the dark phase. These effects required both estrogen receptor alpha and beta activation and were mediated by estrogen receptor signaling within the median preoptic nucleus (MnPO). Direct infusion of E2 into the MnPO was sufficient to replicate systemic effects, while local infusion of the pure estrogen receptor antagonist ICI 182,780 (Fulvestrant) attenuated them. Progesterone did not augment E2's actions, and males showed no sleep-wake changes in response to E2, highlighting sex-specific mechanisms. The MnPO is a critical site where E2 regulates sleep-wake behavior. These findings provide a neurobiological framework for understanding how ovarian hormones contribute to sleep disruptions in women, offering potential therapeutic targets for sleep disorders related to hormonal changes.

Increasing evidence points towards sleep apnoea as a modifiable risk factor for neurodegeneration. This study investigates the longitudinal effect of sleep apnoea on brain structures in a general population. Data from the Study of Health in Pomerania with baseline laboratory-based polysomnography and MRI (2008-2012), and 7-year follow-up MRI (2016-2019) was used. Sleep apnoea was characterized by the apnoea-hypopnea index (AHI), oxygen desaturation index (ODI), mean sleep oxygen saturation (SpO2), and arousal index; subjective sleep quality using the Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index. Total brain volume, regional and total grey matter thickness, white matter hyperintensity burden, and brain age were derived from 1.5 tesla T1 and FLAIR sequences. Associations between sleep apnoea and follow-up MRI measures were examined using linear regression adjusted for age, sex, intracranial volume, total sleep time, follow-up duration, and baseline MRI values. Restricted cubic splines were used in all continuous variables to model non-linear effects. 387 participants were included (age 50.7 ± 12.4 years, 47.3% female). Neither AHI nor ODI showed significant longitudinal effects. Lower SpO2 was associated with reduced total brain volume, while a higher arousal index was linked to increased brain age and decreased global and regional grey matter thickness. Subjective sleep quality correlated with total brain volume changes. Unlike prior cross-sectional findings, traditional sleep apnoea indices were not associated with structural brain changes over 7 years. Instead, sleep fragmentation emerged as a key factor in brain atrophy. Targeting sleep fragmentation may offer neuroprotective benefits.

Most studies of neighborhood context and sleep health emphasize direct effects and fail to account for the role of genetics. In this paper, we draw on the socioecological model to examine the interplay of genetics, neighborhood context, and sleep health. We specifically examine the independent and joint effects of genetic risk scores (GRS) and perceived neighborhood disorder on sleep duration. We combine genomic and cross-sectional survey data from the All of Us Research Program, a non-probability sample of 22,575 adults of European ancestry living in the United States. We use the sleep duration-increasing risk allele count for 78 genome-wide SNPs to construct weighted GRS. Our analyses include an index of perceived neighborhood disorder and an objective measure of sleep duration based on wrist actigraphy. GRS are inversely associated with neighborhood disorder, positively associated with continuous sleep duration, and inversely associated with the odds of short sleep. Neighborhood disorder is inversely associated with continuous sleep duration and positively associated with the odds of short and long sleep. The association between GRS and sleep duration (continuous and categorical) is invariant across levels of neighborhood disorder. Our analyses confirm the independent direct effects of GRS and neighborhood disorder on sleep duration. Our findings extend the socioecological model by assessing the role of genetics in the study of neighborhood context and sleep health. Although we revealed a gene-environment correlation between GRS and perceived neighborhood disorder, there was little indication of genetic confounding and no evidence of gene-environment interaction.

In patients with acute myocardial infarction (AMI), early use of minute-ventilation triggered adaptive servo-ventilation (ASVmv) for sleep-disordered breathing (SDB) has been proposed as a therapeutic intervention to reduce infarct expansion. This study aims to assess the efficacy of ASVmv in modulating nocturnal hypoxaemic burden and evaluate its association with infarct size. This ancillary analysis of the multicentre, randomised, open-label TEAM-ASV I trial included patients with first-time AMI and SDB, defined by an apnoea-hypopnoea index (AHI) ≥15 events·h-1 assessed with polygraphy. Infarct size was quantified via cardiac magnetic resonance imaging. Nocturnal hypoxaemic burden was quantified by the time in bed spent with oxygen saturation below 90% (T90) and further decomposed into desaturation-related components (T90desaturation) and non-specific drifts (T90non-specific). Thirty-five patients with infarct size 15.5±6.9% of left ventricular mass were randomised to early ASVmv treatment in addition to standard care of AMI (n=16) and standard care alone (control, n=19). Compared with baseline, all components of hypoxaemic burden, T90 (9.25% [1.34-16.32] vs. 0.03% [0.00-1.72; p=0.003], T90desaturation (0.72% [0.49-7.97] vs. 0.00% [0.00-0.06]; p<0.001), and T90non-specific (4.75% [0.38-10.30] vs. 0.00% [0.00-1.73]; p<0.001) were significantly reduced during the ASVmv treatment initiation night. After 12 weeks, ASVmv treatment showed lower median T90desaturation compared to the control group (ASVmv: 0.10% [0.00-0.40] vs. control: 0.40% [0.22-1.80]; p=0.020) but not T90non-specific. T90 (rs=0.437, p=0.023) and its component, T90non-specific, were both associated with infarct size (rs=0.424; p=0.028). ASVmv treatment suppresses the sleep apnoea-related nocturnal hypoxaemic burden following acute myocardial infarction. Higher T90, particularly non-specific drifts in SpO₂, were associated with larger infarct size. These findings are exploratory and should be regarded as hypothesis-generating. NCT02093377.

The tendency to procrastinate bedtime is associated with poorer sleep and wellbeing. However, day-specific effects of bedtime procrastination are rarely studied and may differ by whether an individual has school/work the next day versus the flexibility to wake up later. We tested the hypothesis that going to bed later than intended would be associated with shorter sleep and worse next-day mood on school nights, but not non-school nights, in residential college students. Actigraphy-estimated sleep timing and duration were measured for 2weeks in 104 university students. Daily diaries recorded instances of going to bed later than intended, morning mood, and daytime sleepiness. Mixed effects models tested associations of delaying bedtime with same-night sleep duration and next-day mood and sleepiness, adjusting for demographics, chronotype, and school start time. Students went to bed later than intended on 54% of all nights. Individuals who delayed their bedtime more frequently had poorer self-rated sleep, higher pre-sleep arousal, and higher depression scores. Going to bed later than intended was associated with shorter sleep by 0.91h on school nights and 0.86h on non-school nights because there was no compensatory delay in wake-up time. Next-morning mood and daytime sleepiness were worse compared with nights with no bedtime delay. Residential college students who went to bed later than intended showed deficits in sleep duration and wellbeing irrespective of whether they needed to wake up for classes. Interventions to prevent bedtime procrastination may help students to achieve better sleep and mental health.

Alterations in sleep-wake patterns are well-recognized features of overt alpha-synucleinopathies. However, their presence in prodromal stages, characterised by isolated REM sleep behavior disorder (iRBD), remains controversial, and their association with clinical symptoms and imaging risk factors has been underexplored. In this study, we used seven-day ambulatory circadian monitoring to characterize circadian and sleep-wake disturbances in a well-characterised sample of forty-two patients with video-polysomnography-confirmed iRBD and twenty-three healthy controls (HC). We investigated the associations between circadian disturbances and non-motor clinical symptoms, assessed in a comprehensive neuropsychological protocol, alongside imaging proxies of glymphatic system functioning, namely the Diffusion Tensor Imaging Along the Perivascular Spaces (DTI-ALPS) index, and volume of perivascular spaces and choroid plexuses. Moreover, we assessed the associations between circadian alterations and striatal dopaminergic uptake in the most affected putamen, a well-established risk factor for conversion to alpha-synucleinopathies, as assessed with presynaptic dopaminergic imaging. Patients with iRBD exhibited reduced diurnal physical activity, along with reduced amplitude and increased fragmentation of the sleep probability and motor activity rhythms. Circadian alterations correlated with greater neuropsychiatric symptoms and reduced psychomotor and mental speed. Patients with iRBD exhibited a decreased DTI-ALPS and larger volume of perivascular spaces, but only the former was associated with sleep impairment. Decreased putaminal dopaminergic uptake was associated with rest-activity rhythm fragmentation. These results show that circadian alterations are observed in early stages of neurodegeneration and are associated with clinical and imaging risk markers of conversion to alpha-synucleinopathies, posing them as possible targets for intervention in prodromal disease stages.

This study examined whether basal electromyographic (EMG) amplitude during sleep is altered in patients with isolated REM sleep behavior disorder (iRBD) and its relationship to disease progression, as well as changes across the sleep cycle. Baseline polysomnograms collected from 95 iRBD patients (15 converters, 80 non-converters) and matched 24 controls were analyzed. EMG amplitude was calculated from submentalis recordings across all sleep stages using 3-second mini-epochs, with REM sleep further classified as REM sleep without atonia (RWA) and non-RWA (RA) according to the presence of "any" RWA events. Kaplan-Meier analysis assessed phenoconversion risk, and EMG amplitude was compared between early and late sleep cycles within each group. Group comparisons with post-hoc adjustment showed that EMG amplitude in RA and RWA was higher in non-converters than controls (adj-p<.001), while converters showed further increases of EMG amplitude in N2 and N3 (adj-p<.045). RA amplitude was higher in converters than non-converters (adj-p=.02). Increased EMG amplitude in N2, N3, and RA was associated with higher phenoconversion risk (p<.05). EMG amplitude remained stable between early and late cycles during RA in both iRBD and controls. In contrast, iRBD patients showed a significant decrease in EMG amplitude during late cycles in N2 (p<.009). Elevated basal EMG amplitude during both REM and NREM sleep in iRBD patients shows potential as a prognostic marker, indicating muscle tone dysregulation beyond REM atonia loss and underscoring the need to consider broader sleep stages in iRBD evaluation.