Sleep最新文献

Study objectives: Evaluate a triaged stepped-care strategy among adults 50 and older with insomnia disorder.

Methods: Participants (N = 245) were classified at baseline by a Triage Checklist. Those projected to do better if they start treatment with therapist versus digitally delivered CBT-I (tCBT-I vs dCBT-I) constituted the YES stratum (n = 137); the rest constituted the NO stratum (n = 108). Participants were randomized within stratum to a strategy that utilized only dCBT-I (ONLN) or to a strategy that prospectively allocated the first step of care to dCBT-I or tCBT-I based on the Triage Checklist and switched dCBT-I nonresponders at 2-months to tCBT-I (STEP). Co-primary outcomes were the insomnia severity index (ISI) and the average nightly amount of prescription hypnotic medications used (MEDS), assessed at 2, 4, 6, 9, and 12 months postrandomization.

Results: Mixed effects models revealed that, compared to ONLN, participants in STEP had greater reductions in ISI (p = .001; η2 = 0.01) and MEDS (p = .019, η2 = 0.01). Within the YES stratum, compared to ONLN, those in STEP had greater reductions in ISI (p = .0001, η2 = 0.023) and MEDS (p = .018, η2 = 0.01). Within the ONLN arm, compared to the YES stratum, those in the NO stratum had greater reductions in ISI (p = .015, η2 = 0.01) but not in MEDS. Results did not change with treatment-dose covariate adjustment.

Conclusions: Triaged-stepped care can help guide the allocation of limited CBT-I treatment resources to promote effective and safe treatment of chronic insomnia among middle-aged and older adults. Further refinement of the Triage Checklist and optimization of the timing and switching criteria may improve the balance between effectiveness and use of resources.

Clinical trial information: Name: The RESTING Insomnia Study: Randomized Controlled Study on Effectiveness of Stepped-Care Sleep Therapy.

Trial registration id: NCT03532282. URL: https://clinicaltrials.gov/study/NCT03532282.

Study objectives: Discerning the differential contribution of sleep behavior and sleep physiology to the subsequent development of posttraumatic-stress-disorder (PTSD) symptoms following military operational service among combat soldiers.

Methods: Longitudinal design with three measurement time points: during basic training week (T1), during intensive stressed training week (T2), and following military operational service (T3). Participating soldiers were all from the same unit, ensuring equivalent training schedules and stress exposures. During measurement weeks soldiers completed the Depression Anxiety and Stress Scale (DASS) and the PTSD Checklist for DSM-5 (PCL-5). Sleep physiology (sleep heart-rate) and sleep behavior (duration, efficiency) were monitored continuously in natural settings during T1 and T2 weeks using wearable sensors.

Results: Repeated measures ANOVA revealed a progressive increase in PCL-5 scores from T1 and T2 to T3, suggesting an escalation in PTSD symptom severity following operational service. Hierarchical linear regression analysis uncovered a significant relation between the change in DASS stress scores from T1 to T2 and subsequent PCL-5 scores at T3. Incorporating participants' sleep heart-rate markedly enhanced the predictive accuracy of the model, with increased sleep heart-rate from T1 to T2 emerging as a significant predictor of elevated PTSD symptoms at T3, above and beyond the contribution of DASS stress scores. Sleep behavior did not add to the accuracy of the model.

Conclusion: Findings underscore the critical role of sleep physiology, specifically elevated sleep heart-rate following stressful military training, in indicating subsequent PTSD risk following operational service among combat soldiers. These findings may contribute to PTSD prediction and prevention efforts.

Study objectives: The association between snoring, a very common condition that increases with age, and dementia risk is controversial. We aimed to investigate the observational and causal relationship between snoring and dementia, and to elucidate the role of body mass index (BMI).

Methods: Using data from 451 250 participants who were dementia-free at baseline, we examined the association between self-reported snoring and incident dementia using Cox proportional-hazards models. Causal relationship between snoring and Alzheimer's disease (AD) was examined using bidirectional two-sample Mendelian randomization (MR) analysis.

Results: During a median follow-up of 13.6 years, 8325 individuals developed dementia. Snoring was associated with a lower risk of all-cause dementia (hazard ratio [HR] 0.93; 95% confidence interval [CI] 0.89 to 0.98) and AD (HR 0.91; 95% CI 0.84 to 0.97). The association was slightly attenuated after adjusting for BMI, and was stronger in older individuals, APOE ε4 allele carriers, and during shorter follow-up periods. MR analyses suggested no causal effect of snoring on AD; however, genetic liability to AD was associated with a lower risk of snoring. Multivariable MR indicated that the effect of AD on snoring was primarily driven by BMI.

Conclusions: The phenotypic association between snoring and lower dementia risk likely stems from reverse causation, with genetic predisposition to AD associated with reduced snoring. This may be driven by weight loss in prodromal AD. Increased attention should be paid to reduced snoring and weight loss in older adults as potential early indicators of dementia risk.

Study objectives: To investigate the association between maternal early pregnancy body mass index (BMI) and risk of offspring insomnia.

Methods: We conducted a nationwide cohort study among 3 281 803 singleton live births in Sweden born 1983-2015. Using national registries with prospectively recorded information, we followed participants for an insomnia diagnosis from 2 to up to 35 years of age. We compared insomnia risks by early pregnancy BMI categories using hazard ratios (HR) with 95% confidence intervals (CI) from adjusted Cox models. To assess unmeasured shared familial confounding, we conducted sibling-controlled analyses among 1 724 473 full siblings and studied the relation of maternal full sisters' BMI and insomnia risk in 1 185 998 offspring.

Results: There were 7154 insomnia diagnoses over a median follow-up age of 17.9 years. Compared with women with normal BMI, adjusted HR (95% CI) of offspring insomnia for early pregnancy BMI categories overweight, obesity class I, and obesity classes II or III were, respectively, 1.22 (1.14, 1.30), 1.60 (1.45, 1.77), and 2.11 (1.83, 2.45). Corresponding adjusted HR (95% CI) in sibling comparisons were, respectively, 1.32 (1.05, 1.65), 1.48 (1.03, 2.14), and 1.56 (0.91, 2.65). Associations with maternal sisters' BMI were attenuated, suggesting a weak role for unmeasured shared factors. Other pregnancy, birth, and neonatal complications were associated with the risk of insomnia in offspring but did not substantially mediate the association.

Conclusions: The dose-response relation between maternal overweight and obesity severity with offspring insomnia risk is not fully explained by shared familial factors.

Histamine, a neurotransmitter, plays a predominant role in maintaining wakefulness. Furthermore, our previous studies showed that histamine N-methyltransferase (HNMT), a histamine-metabolizing enzyme, is important for regulating brain histamine concentration. However, the effects of pharmacological HNMT inhibition on mouse behavior, including the sleep-wake cycle and cataplexy, in a mouse model of narcolepsy have not yet been investigated. In the present study, we investigated the effects of metoprine, an HNMT inhibitor with high blood-brain barrier permeability, in wild-type (WT) and orexin-deficient (OxKO) narcoleptic mice. Metoprine increased brain histamine concentration in a time- and dose-dependent manner without affecting peripheral histamine concentrations. Behavioral tests showed that metoprine increased locomotor activity in both novel and familiar environments, but did not alter anxiety-like behavior. Sleep analysis showed that metoprine increased wakefulness and decreased non-rapid eye movement (NREM) sleep through the activation of the histamine H1 receptor (H1R) in WT mice. In contrast, the reduction of rapid eye movement (REM) sleep by metoprine occurred independent of H1R. In OxKO mice, metoprine was found to prolong wakefulness and robustly suppress cataplexy. In addition, metoprine has a greater therapeutic effect on cataplexy than pitolisant, which induces histamine release in the brain and has been approved for patients with narcolepsy. These data demonstrate that HNMT inhibition has a strong effect on wakefulness, demonstrating therapeutic potential against cataplexy in narcolepsy.