Mathematical and Computer Modelling

Abstract Purpose of Review Sleep rhythms - particularly the coupling between cortical slow oscillations, thalamo-cortical spindles and hippocampal ripples - are proposed to contribute to multi-regional interactions crucial for memory consolidation. Animal studies are optimal to assess activity of deeper lying brain structures. Our systematic review, aims to assess animal studies employing closed-loop stimulation in the context of sleep-associated memory consolidation, to compare findings and methodologies, and provide suggestions for future research from a translational perspective. Recent Findings Results highlight the functional relevance of temporal coupling between sleep rhythms, but also disclose a high temporal and spatial specificity of responses, and dependence on the firing of neuromodulatory nuclei. Summary Closed-loop stimulation procedures present a means to experimentally investigate causal relationships between network activity and behavior, but also network neuroplasticity. It is suggested to investigate the possibility of substituting visual detection steps by machine learning. Furthermore, the inclusion of female subjects is encouraged.

Abstract Purpose of Review Despite advancements in basic circadian research, development of new diagnostic and treatment strategies for circadian rhythm sleep-wake disorders (CRSWDs) has been slow. Here, we review the most recent innovations in human circadian assessment and emerging new therapies for CRSWDs. Recent Findings Researchers have improved existing circadian assessment methods to overcome logistical barriers and developed novel circadian assessment methods. New treatments for CRSWDs involve pharmacological and behavioral treatments that modulate circadian phase, amplitude, and/or robustness of the central circadian clock. Summary Commercialization of these emerging tools will require overcoming barriers, such as additional testing to confirm the underlying pathology and mechanism of action of potential treatments. Clinicians and scientists are also called to survey adjacent fields and adopt existing diagnostic tools that may offer diagnostic clarity in CRSWDs. Lastly, we must continue to advocate for medical insurance coverage of current and future tools and technologies to improve patient care.

Abstract Purpose of Review Sleep is dynamic across the lifespan, influenced by brain maturation, neurophysiology, hormones, and cognitive processes. Sleep behaviors influenced by physiological and external factors can also impact sleep health. As sleep plays a mechanistic role in health across the lifespan, understanding when and how to intervene to benefit health is essential. Recent Findings Recent research has advanced our understanding of sleep across three domains: patterns, neurophysiology, and behaviors. Highlights include (1) Early childhood nap cessation is thought to relate to medial temporal lobe network maturation and underlie long-term hippocampal-dependent memory development. (2) Chronotype misalignment is a key factor in sleep deficits and social jetlag. (3) Older adult daytime sleep has complex effects on health, at times beneficial while others, potentially maladaptive. (4) Longitudinal sleep oscillation trajectories are starting to be investigated and indicate neurophysiology could be interpreted as indicative of brain maturation in development. (5) In adults, sleep quality and macrostructure trajectories show high variability, emphasizing distinctive traits in shaping sleep and its lifespan trajectories. (6) Neighborhood and socioeconomic factors influence sleep health across all ages. (7) In older adults, associations between loneliness and poor sleep are being unpacked. Summary This recent research, while comprehensively describing our current understanding of sleep trajectories across the lifespan, emphasizes the need to expand current approaches to longitudinal measurement studies that cross age-spans. Expanding will enhance our ability to mechanistically determine the temporal and causal relations between the multiple dimensions of sleep (i.e., patterns, behaviors, and physiology) and outcomes in sleep health.

We examined literature from PubMed and Google Scholar to summarize the available evidence on pharmacological and nonpharmacological interventions to manage sleep disturbances in individuals with substance use disorders, with a focus on alcohol, opioids, cannabis, and nicotine use disorders. Overall, 82 studies were included in this review. For the studies included, the year of publication ranged from 1977 to 2023. Several pharmacological agents showed preliminary efficacy and tolerability in treating sleep disturbances in patients with substance use disorders, particularly in the context of alcohol and opioid use. Further well-powered studies with longer duration of follow-up are required. There was insufficient evidence to support the use of specific agents to treat sleep difficulties in cannabis and nicotine use disorders, although some medications showed initial promise. Nonpharmacological interventions such as cognitive behavioral therapy for insomnia (CBT-I) could serve as a valuable complement to pharmacotherapy in patients with substance use disorders; however, further research is needed in disorders other than alcohol dependence. Sleep disturbance was found to be a common, easily identifiable, and potentially modifiable risk factor in patients with substance use disorders. Recognition and treatment of sleep disturbance in this population can impact treatment participation, quality of life, and relapse risk. Evidence for pharmacological agents in this space is growing. Treatment options vary depending on the type of substance use disorders and clinicians need to balance potential risks and benefits in the individual patient.

In this article, we review recent literature on the associations between sleep irregularity and a variety of health outcomes and discuss potential mechanisms mediating these relationships. Greater variability in sleep patterns is associated with detriments in sleep quality, circadian rhythms, performance, and both mental and physical health across the lifespan, often beyond contributions from sleep duration alone. A growing consensus in the literature indicates that regularity in sleep timing and duration is important for maintaining optimal health and performance. A variety of published metrics have been proposed to quantify sleep irregularity, and different metrics may be applied based on the types of data available, sample size, length of data collection period, and specific question under investigation. Experimental and longitudinal data establishing a direct causal effect of sleep irregularity on health are limited and remain an important area for future research to develop effective interventions to regularize sleep patterns for better overall health and well-being.

Sleep impairment due to chronic pain is linked to functional impairment and often inadequately addressed with current treatments leading some to seek alternative therapies, including cannabis. The factors associated with chronic pain and sleep impairments are disproportionately experienced by individuals from racial/ethnic minorities, of low socioeconomic status, who live in noisy, chaotic neighborhoods, and who have poor health care access. First, we describe the limited evidence for cannabis to manage pain and pain-related sleep impairment. Second, we highlight how research might exacerbate health inequities due to systematic biases in the populations and products being studied to determine cannabis efficacy. The preponderance of evidence is based on predominantly White samples, a limited subset of cannabis forms, and have been of lower quality. More inclusive, generalizable studies that reflect the real-world ways that individuals use cannabis and evaluate how the social determinants of health interplay with the risks for pain-related sleep impairments are needed.

The purpose of this review is to provide an overview of potential mechanisms mediating the bi-directional relationship between sleep and neurodegenerative diseases such as Alzheimer’s disease. We provide updates on previously proposed mechanisms and identify new mechanisms particularly concerning how sleep disturbances affect memory-related neural circuits. In this review, we focus on the multiple mechanisms that potentially mediate the relationship between sleep and Alzheimer’s disease. We present updates for previously hypothesized mechanisms such as sleep-related changes in production/release and clearance of amyloid-β and tau proteins as well as more recently proposed mechanisms relating to tau phosphorylation, the orexin system, astrocytes, and microglia. We also highlight how disruptions in sleep EEG oscillations that underlie memory-related neural circuits, such as slow wave activity, theta bursts, sleep spindles, and gamma ripples, change in Alzheimer’s disease. Disturbed sleep increases Alzheimer’s disease risk via multiple potential mechanisms that suggest multiple targets to test approved and effective treatments of sleep disorders to prevent or delay Alzheimer’s disease.

Abstract Purpose of Review Obstructive sleep apnea (OSA) affects at least 1 billion people worldwide, and its increasing prevalence is alarming considering an association to comorbidities such as cardiovascular disease (CVD) and to demonstrated health disparities. This raises concerns regarding the current diagnostic standards, which are also impacted by disparities. The current review was aimed at identifying limitations in the apnea-hypopnea index (AHI), the primary clinical indicator of OSA severity, and analyzing recent alternatives. In addition, the association between OSA and CVD was discussed, and, considering the role of intermittent hypoxia, solutions were proposed for improving OSA diagnosis. Recent Findings Based on a review of current literature, alternative metrics to the AHI such as the hypoxia burden, sleep apnea-specific pulse rate, and oxygen desaturation rate were shown to be correlated with indicators of CVD in OSA patients. A recent mathematical study also presents the possibility of a model-based metric to eliminate existing bias in diagnostics and to provide a more accurate quantification of tissue hypoxia. Summary The analyzed studies give incentive to look beyond current clinical standards in OSA. Through this review, we motivate the use of mathematical modeling as a future avenue to improve OSA diagnosis with a hypoxia-based approach.

This review aims to (a) synthesize available cannabis and sleep health literatures to propose a bidirectional risk model, and (b) provide a research agenda addressing priority literature gaps. Sleep problems prompt self-medication with cannabis, which inadvertently maintains or worsens sleep problems due to predictable neurobiological processes. Over time, self-medication behavior may increase to compensate for cannabis tolerance and ongoing sleep problems, ultimately increasing risk for cannabis use disorder and associated consequences. Several theoretical mechanisms may explain self-medication with cannabis for sleep aid, and underlying social determinants may explain sociodemographic variability and disparities. This review proposes a bidirectional model in which cannabis use and sleep health interact in a feed-forward cycle, ultimately maintaining and exacerbating risk in both domains over time. Clinical implications are reviewed for cannabis sleep aid presenting to behavioral medicine settings. A research agenda is proposed spanning domains of epidemiology, bidirectional processes, and transdiagnostic social determinants.

Central sleep apnea (CSA) is associated with increased mortality, particularly in heart failure. This review discusses current treatment options with a focus on different positive airway pressure (PAP) modalities, the clinical implication of continuous PAP (CPAP) failure, and key advancements in adaptive servo-ventilation (ASV). CPAP reduces CSA by about 50% in patients with heart failure with reduced ejection fraction. The remaining patients are considered non-responsive and chronic use of CPAP has been associated with excess mortality. ASV is effective in several forms of CSA. While secondary analyses of the SERVE-HF trial limited its use in patients with predominant CSA and left ventricular ejection fraction < 45%, more recent data from ADVENT-HF using a newer ASV generation targeting peak flow has shown promising results. Physicians should consider the underlying pathophysiology, overall prognosis, and evidence base prior to selecting CSA treatment with CPAP or ASV. Promising pharmaceutical and novel device options require more studies and long-term evidence.

As the global population continues to age, the identification of drivers of suicide risk in older adults is of increasing importance. This manuscript explores the link between insomnia and suicide risk in older adults, highlighting the prevalence of sleep disorders in aging populations and their impact on mental and physical health. Potential mechanisms, both physiological and psychological, linking insomnia to suicide risk are explored. Clinical implications and treatment recommendations regarding the intersection of insomnia and suicide are discussed. Recent meta-analyses have examined whether interventions for sleep disorders are (1) efficacious in the older adult population and (2) have a significant role in reducing suicidal ideation. Results from Huang and colleagues’ (Huang K, Li S, He R, Zhong T, Yang H, Chen L, et al. Efficacy of cognitive behavioral therapy for insomnia (CBT-I) in older adults with insomnia: A systematic review and meta-analysis. Australas Psychiatry. 2022;30(5):592–7. The authors report results from a meta analysis of 14 studies to examine the efficacy of cogntivie behavioral therapy for insomnia in older adults. Significant effects were reported for sleep efficiency, sleep onset latency, wake after sleep onset, and total sleep time indicating that this intervention is efficacious in the older adult population.) analyses of 14 studies suggest that cognitive behavioral therapy for insomnia (CBT-I) is effective in improving sleep quality and reducing insomnia symptoms in older adults, reaffirming that CBT-I is an important tool to treating insomnia in this population. In regard to suicidal ideation, Mournet & Kleiman (Mournet AM, Kleiman EM. A systematic review and meta-analysis on the efficacy of sleep interventions to treat suicidal ideation. J Sleep Res. 2024:e14133. The authors report findings from a meta-analysis that evaluates whether behavioral and pharmacological sleep interventions also reduce suicidal ideation. Findings suggest a small effect such that sleep interventions reduce suicide ideation that did not reach the level of statistical significance. Authors suggest that given the small sample size and heterogeneity of methods that additional work is needed to explore whether sleep interventions have utility as an adjunctive suicide prevention strategy.) further advance the field with their publication of a meta-analysis of eight studies which examined the impact of sleep interventions on the reduction of suicidal ideation. Analyses of the available studies indicates small effects on suicidal ideation that did not reach the level of statistical significance. The authors note, however, that the small sample of studies and heterogeneity of their design calls for further research into the area before conclusions can be drawn. Multiple pathways may contribute to the development and course of suicide risk among older adults. We highlight factors linked to suicidal ideation and behavior, ranging from psychological factors such as depression and cognitive decline, to physiological disruptions in serotonin pathways and circadian rhythm. Screening for insomnia and suicide risk in older adults remains a key part of early identification and intervention to reduce risk and improve quality of life. Making evidence-based interventions to address both insomnia and suicide risk, such as cognitive-behavioral therapy for insomnia, more broadly available is indicated.