Sleep Disorders Research Articles

Ability of Upper Airway Metrics to Predict Obstructive Sleep Apnea Severity: A Systematic Review.

The lack of consensus regarding the association between airway narrowing and the severity of obstructive sleep apnea (OSA) presents a significant challenge in understanding and diagnosing this sleep disorder. The study aimed to systematically review the literature to investigate the relationship between upper airway measurements and the severity of OSA defined by the apnea-hypopnea index (AHI). PubMed, Scopus and Web of Science were systematically searched on the 21st of March 2023 for articles of OSA patients as diagnosed by polysomnography, investigating the correlation between upper airway measurements and AHI using CBCT or MDCT. Quality assessment was done using the New Castle-Ottawa Scale. The results were subsequently synthesized descriptively. The database search identified 1253 results. Fourteen studies, encompassing 720 patients, met the eligibility criteria. Upper airway length showed moderate to weak positive correlation with AHI. Minimal cross-sectional area had varying correlations with AHI, ranging from strong negative to no correlation. Nasopharyngeal volumes showed moderate negative to weak correlations with AHI. Total upper airway volume ranged from strong negative to weak correlation with AHI. Other measurements exhibited weak or very weak correlations with AHI. Among the variables investigated, the minimal cross-sectional area and, to a lesser extent, the volume of the upper airway in OSA patients demonstrated the most promising correlation with the AHI. However, the preponderance of evidence suggests that upper airway length, cross-sectional area and volume as measured by CBCT or MDCT are weak predictors of OSA.

Prevalence of symptoms suggestive of sleep apnea among children and its impact on academic performance

BackgroundObstructive sleep apnea (OSA) is a common condition in pediatrics that requires prompt recognition and management to minimize its negative impact on their health and development. Data on the prevalence of OSA among school-age minors in Jordan is scarce. This study aims to estimate the prevalence of OSA in children and adolescents and identify factors that make them more likely to have OSA and its impact on academic achievement.MethodsThis school‐based cross‐sectional study was conducted from January to March 2023. A questionnaire including information on demographic variables, school performance, and a validated sleep-related breathing disorder (SRBD) scale for pediatrics was distributed to 1798 students in schools all over Amman. The prevalence of OSA (defined as SRBD score > 33%) was reported as a proportion along with its 95% confidence interval.ResultsOut of the 2000 questionnaires distributed, 1798 were analyzed. Among these, 1079 (60%) were from children aged 5 to 10 years, and 719 (40%) were from adolescents aged 11 to 18 years. The prevalence of high risk for OSA (HR-OSA) was higher among adolescents than in children (25.6% vs. 20.8%). Adolescents with unemployed fathers were more likely to be HR-OSA (33.70 vs 17.57%, p < 0.001). In contrast, paternal employment did not affect the prevalence of HR-OSA in children. Sleep talking, bruxism, and sweating during sleep were more common among children with positive SRBD. Nocturnal enuresis (NE) was associated with positive SRBD in children and adolescents. HR-OSA was associated with poor academic performance in both study groups.ConclusionHR-OSA is highly prevalent in Jordanian children and adolescents. HR-OSA can occur alongside other sleep disorders, and it significantly impairs the academic performance of affected individuals. This study found an association between high risk for OSA and other sleeping disorders (sleep talking, sleep bruxism, and sweat during sleeping) and nocturnal enuresis which needs to be confirmed in larger studies.

Sleep and respiratory infections.

Sleep disorders that involve circadian rhythm disruption and sleep-disordered breathing (SDB) such as obstructive sleep apnea (OSA) are closely linked to respiratory infections. SDB leads to a proinflammatory state due to intermittent hypoxia, sleep fragmentation, increased oxidative stress, and elevation of inflammatory mediators such as tumor necrosis factor (TNF), interleukin-6 (IL-6), and C-reactive protein (CRP). Furthermore, inflammatory mediator levels correlate with SDB severity, especially in people with OSA. Nocturnal microaspiration, gastroesophageal reflux, and associated comorbidities (e.g. obesity) increase the risk of community-acquired pneumonia, viral infections such as SARS-CoV-2, respiratory complications, and death. OSA has been associated with post-COVID syndrome. It also increases the risk of postoperative complications in both adults and children. Circadian rhythm disorders such as insomnia predispose to immune disorders and increase the risk of infection. Chronic conditions such as bronchiectasis, with or without concomitant cystic fibrosis, can lead to structural sleep changes and increase the risk of OSA due to chronic cough, arousals, aspirations, hypoxia, upper airway edema, and overexpression of proinflammatory cytokines. The protective effect of treatment for sleep disorders against respiratory infection is currently unknown. However, in people presenting with respiratory infection, it is important to test for SDB to prevent complications.

Clinical manifestations associated with the chronic phase of Chikungunya Fever: A systematic review of prevalence.

The aim of this systematic review of prevalence is to observe and discuss the clinical manifestations of Chikungunya Virus disease in its chronic phase. To be eligible, the observational studies should accompany the individuals for at least six months. The research was conducted using electronic databases MEDLINE and EMBASE. The methodological quality was evaluated using the "Joanna Briggs Institute's critical appraisal checklist for studies reporting prevalence data" tool. The search has found 175 articles. The application of the inclusion criteria defined a total of 29 selected studies. From the included studies, only one did not present arthralgia as a prevalent symptom in the chronic phase. Other signs and symptoms observed were: fatigue; sleep disorders; myalgia; skin lesions; depression; digestive disorders. Because it is an often incapacitating symptom, arthralgia can affect the individuals' quality of life, with implications in their social and work life. Since the chronic phase is common in infected individuals, all levels of health care should be prepared to monitor, in the medium to long term, the patients affected by this condition.

Recommendations of the DGRh Committee on Complementary Medicine and Nutrition on the application of selected phytotherapeutic drugs and herbal medicines in rheumatology

Herbal preparations and phytotherapeutic substances are offered for symptoms and diseases of the rheumatic spectrum and are often intensively advertised in the lay press. The German Society for Rheumatology and Clinical Immunology (DGRh) Committee on Complementary Medicine and Nutrition reviewed the scientific literature on selected over the counter preparations and prescription phytotherapeutic substances and examined the possibilities for their use in rheumatology. In an online meeting of the Committee on 8 February 2023 alist of herbal preparations that are frequently used in rheumatology (mostly as self-medication) was drawn up. Each member of the committee then carried out aliterature search on one or two substances and summarized the results according to adefined matrix. Research was carried out on borage oil, stinging nettle preparations, cannabis preparations and preparations of dog rose, rosemary, saffron and willow bark. The data on the mixed preparation Phytodolor® (Bayer Vital GmbH, Germany) were also examined. The results were reviewed by a circulation procedure and approved in two further online meetings of the Committee. After review by the DGRh board, the recommendations were transferred to the professional organization's website. Even though there are reports of anti-inflammatory or immunological effects in vitro and/or in animal models for all the plant substances examined, the evidence for aclinically relevant benefit is sparse. None of the preparations investigated has atherapeutic efficacy that justifies its use in inflammatory joint diseases. Herbal preparations based on saffron and rosemary are generally not recommended. Borage oil from seeds can be taken in standardized form as part of ahealth-conscious diet but is not expected to have any significant anti-inflammatory effect. Rheumatologists need not advise against Phytodolor® or preparations based on stinging nettle, willow bark or dog rose, which are taken on the patient's initiative for degenerative joint diseases, if asensible therapy concept is otherwise adhered to. There is insufficient evidence to prescribe medicinal cannabis for inflammatory rheumatic diseases for disease modification or symptomatic therapy. In individual cases, however, its use to reduce chronic pain, particularly neuropathic pain and sleep disorders and to reduce opiate consumption may be justified. Even if the herbal preparations presented here must be considered in adifferentiated manner for rheumatology practice, the value of phytotherapy for the discipline is low.

Evidence for domain-general arousal from semantic and neuroimaging meta-analyses reconciles opposing views on arousal.

Arousal refers to changes in brain-body state underpinning motivated behavior but lacks a proper definition and taxonomy. Neuroscience and psychology textbooks offer surprisingly different views on what arousal is, from a global brain-wide modulation of neuronal activity to a multidimensional construct, with specific brain-body patterns tuned to a given situation. The huge number of scientific articles mentioning arousal (~50,000) highlights the importance of the concept but also explains why such a vast literature has never been systematically reviewed so far. Here, we leverage the tools of natural language processing to probe the nature of arousal in a data-driven, comprehensive manner. We show that arousal comes in seven varieties: cognitive, emotional, physiological, sexual, related to stress disorders, to sleep, or to sleep disorders. We then ask whether domain-general arousal exists at the cortical level, and run meta-analyses of the brain imaging literature to reveal that all varieties of arousal, except arousal in sleep disorders for lack of data, converge onto a cortical network composed of the presupplementary motor area and the left and right dorsal anterior insula. More precisely, we find that activity in dysgranular insular area 7 (Jülich atlas), the region with the highest convergence across varieties of arousal, is also specifically associated with arousal. The domain-general arousal network might trigger the reorganization of large-scale brain networks-a global mechanism-resulting in a context-specific configuration-in line with the multidimensional view. Future taxonomies of arousal refining the alignment between concepts and data should include domain-general arousal as a central component.

Fibromyalgia: Understanding, Diagnosis and Modern Approaches to Treatment

Fibromyalgia (FM) is a chronic condition characterized by generalized musculoskeletal pain associated with other symptoms, especially sleep and mood disorders, fatigue, and cognitive dysfunctions. The etiopathogenesis of FM is not sufficiently known, and regardless of numerous research, the clinical presentation is nonspecific, which makes it difficult to approve a timely diagnosis and, subsequently, an adequate therapeutic approach. Genetic, hormonal, immunological, and environmental factors are cited as potential factors in the development of this condition. Diagnosis is based on a clinical approach and known diagnostic criteria, while additional methods, such as radiographic, magnetic resonance, or laboratory analyses, can be useful to exclude other conditions. The heterogeneity of FM significantly impacts both diagnosis and treatment, as it presents a wide spectrum of symptoms that vary in severity, combinations, and underlying contributing factors. This variability is a challenge for clinicians and requires a holistic, comprehensive, multidisciplinary, patient-centered approach. According to EULAR recommendations (The European League Against Rheumatism) from 2016, treatment begins with patient education and involves the simultaneous application of pharmacological and nonpharmacological treatments. The application of only pharmacological or nonpharmacological treatment is most often not successful. Due to differences in pain threshold, psychological factors, and comorbidities, patients may respond differently to the same interventions. Although there is no universal treatment, this review brings up the fact that the timely recognition of symptoms and a tailored treatment with a patient-centered plan can significantly improve the quality of life of patients.

Optimal CNN Model for Obstructive Sleep Apnea Detection using Particle Swarm Optimization

Obstructive Sleep Apnea (OSA) is a prevalent sleep disorder with significant health risks. It is characterized by the narrowing of the upper airway during sleep, leading to vibrations in the airway structures and the production of snoring sounds. Recently, Convolutional Neural Networks (CNNs) have been leveraged to extract meaningful features from snoring sound data, enabling early and accurate detection of OSA. The effectiveness of these neural network optimizations depends on the starting values of the model, the gradient algorithm used, and the complexity of the problem. This study introduces an improved Particle Swarm Optimization (PSO) strategy that linearly adjusts the learning rate coefficient to enhance accuracy and convergence speed. Our approach was evaluated on a collected and pre-processed dataset based on the PSG-Audio database. Experimental results demonstrate that our method significantly outperforms the conventional optimization algorithm and existing PSO techniques, achieving a remarkable accuracy of 99.1%. These findings confirm the potential of our optimized model for OSA detection.

Dietary Magnesium Intake Is Associated With Self-Reported Short Sleep Duration but Not Self-Reported Sleep Disorder.

Sleep disturbances have become increasingly prevalent in modern society. Research suggests that a deficiency in magnesium (Mg) may contribute to sleep disturbances. This study aims to investigate the association between daily Mg intake and self-reported sleep duration and sleep disorders using data from the National Health and Nutrition Examination Survey (NHANES). The study dataset includes participants from five cycles (2009-2018) of NHANES. The associations between Mg intake and sleep duration are analyzed using weighted logistic regression. Baseline characteristics of 21,840 participants were analyzed. Mg intake was independently associated with sleep duration (OR = 1.07, 95% CI (1.01-1.14), p = 0.024). Higher quartiles of Mg intake from food were associated with normal sleep duration. However, Mg intake from food in participants with self-reported sleep disorders did not differ from those without sleep disorders (OR = 0.96, 95% CI (0.90-1.03), p = 0.238). Among 3923 participants with Mg supplementation data, no significant differences were found between the top and bottom 50% Mg supplementary groups regarding sleep duration or disorders. Dietary Mg intake is independently associated with self-reported short sleep duration but not with self-reported sleep disorders. Mg supplementation is not associated with either self-reported sleep duration or sleep disorders.

Sleep difficulties related to psychopathology and neurocognition in people with 22q11.2 deletion syndrome.

The 22q11.2 Deletion Syndrome (22q11.2DS) is a multisystem genetic disorder with prominent sleep disturbances, neuropsychiatric conditions and neurocognitive challenges. Poor sleep can impact cognitive development, psychopathology and daily functioning. An integrative approach in clinical settings can help link these manifestations and suggest interventions. A comprehensive sleep interview was conducted with 100 affected individuals and their parents, complemented with electronic health record review. Independent psychiatric and neurocognitive assessments were conducted in 92 participants, divided into Good Sleeper (score 1-4) and Poor Sleeper (score ≥ 5) groups based on the Pittsburgh Sleep Quality Index (PSQI). Sleep disorders were common, 78% of participants met International Classification of Sleep Disorders criteria. Most prevalent were Insomnia, Sleep Disorder Breathing, Delayed Sleep Phase Disorder and Restless Leg Syndrome. 74% of participants met criteria for at least one current psychiatric disorder. Poor Sleepers had lower Global Assessment of Function (GAF), higher severity of psychosis positive, negative, and general symptoms, and lower performance efficiency on executive, spatial memory, complex cognition and social cognition tests. Mediation models showed that association of psychosis scores and GAF were mediated by PSQI and the association between PSQI and GAF was mediated by psychosis scores. Sleep disorders are prevalent in individuals with 22q11.2DS and impact psychiatric manifestation and neurocognitive performance. Results suggest a possible "vicious cycle " whereby disordered sleep is associated with increased psychosis which, in turn, results in worsening sleep, all affecting GAF. Identification of sleep disorders can facilitate appropriate interventions reducing burden of psychiatric symptoms and improving cognition and functioning.

Personality and Sleep Psychopathology: Associations Between the DSM-5 Maladaptive Trait Domains and Multiple Sleep Problems in an Adult Population.

Given the lack of sufficient studies exploring the nature of sleep problems from the perspective of the alternative model of personality disorders (AMPD) proposed by the DSM-5, the present study is aimed at determining the associations between five trait domains such as negative affectivity and sleep problems (insomnia, parasomnia, hypersomnia, circadian rhythm sleep disorder, restless legs syndrome, and sleep-disordered breathing) in an adult population. Adults aged 18-65 from western Iran were invited to the study via virtual platforms (N = 928; 62% female) and responded online to the Brief Form of Personality Inventory for DSM-5 and the Holland Sleep Disorder Questionnaire to assess sleep problems. The regression analyses indicated that the AMPD trait domains could significantly predict both specific sleep problems (R2 ranges from 0.13 to 0.17; all p ≤ 0.001) and total score of sleep problems (R2 = 0.23; p < 0.001). Psychoticism (β ranges from 0.26 to 0.39; all p < 0.001) and negative affectivity (β ranges from 0.14 to 0.29; all p ≤ 0.002) were the strongest specific domains associated with all sleep problems. The findings highlighted links between maladaptive domains of the AMPD and multiple sleep problems. The unique profiles of each sleep problem are useful in selecting treatments tailored to specific sleep problems in adults.

The relationship between pain, sleep quality, and care dependency in older adults living in a long-term care facility

BackgroundDue to the frequency of pain, sleep disorders and the complexity of their associated factors, the diagnosis of these disorders may be of great importance in identifying factors linked to care dependency in older people staying in long-term care facilities. The aim of the study was to investigate the relationship between pain, sleep quality, and care dependency in older adults living in a long-term care facility.MethodsThe study was conducted among older people staying in a long-term care facility between October 2022 and September 2023. The study used a survey questionnaire including questions about demographic and social characteristics, clinical condition and the following scales: ADL, IADL, GSD-15, GPM-24, CDS, PSQI.ResultsThe analysis showed a statistically significant relationship between the deterioration of sleep quality by 1 unit and: an increase in the level of pain (B = 0.68; SE = 0.17; 95% CI [0.38; 1.10]), dependency in ADL (B = -0.09; SE = 0.04; 95% CI [-0.17; -0.02]), feeling depressed (B = 0.18; SE = 0.06; 95% CI [0 0.06, 0.31]) and care dependency (B = -0.78, SE = 0.24, 95% CI [-1.25, -0.31]). A statistically significant effect was noted between: pain level (B = -0.18; SE = 0.06; 95% CI [-0.30; -0.05], dependency in ADL (B = 1.98; SE = 0.35; 95% CI [1.28; 2.68]), instrumental activities of daily living (B = 1.86; SE = 0.28; 95% CI [1.30; 2.42]], feelings of depression (B = -0.96; SE = 0.17; 95% CI [-1.30; -0.62]) and care dependency.ConclusionsThe study is a valuable addition to research showing a strong link between pain, sleep quality and care dependency. The results support the need for a holistic approach in assessing pain, sleep quality, care dependency in older adults living in a long-term care facility.

Risk of developing sleep disorders and psychologic comorbidity in children with inflammatory skin diseases - a population-based study.

Inflammatory skin diseases such as atopic dermatitis (AD), psoriasis and urticaria are associated with impaired mental health and sleep. In children the risk of developing these comorbidities is still poorly evaluated. Retrospective data analysis of a US Collaborative Network including children of 55 Health care providers was performed. Data from electronic health records of patients with a diagnosis of either AD, psoriasis, or urticaria, as well as a control cohort were retrieved in an anonymized batch format and propensity score matched. Children with psoriasis had a 3.2-fold higher risk for hypersomnia, 2.1-fold higher for sleep apnea, 1.8-fold higher for fatigue and 1.9-fold higher for depression. Children with urticaria (acute or chronic) and AD had a 1.7-fold higher risk for sleep disorders, 1.6 higher for anxiety disorders and 1.4-fold higher for insomnia. AD children had a 1.5-fold higher risk for anxiety disorders. Electronic health insurance data are not subject to random sampling of the general population and potential misdiagnosis is possible. Children with inflammatory skin diseases were at a higher risk for sleep psychological disorders. Thus, regularly performed screenings and appropriate treatment initiation might potentially prevent mental and physical health consequences and secure improved life quality.

Role of OX/OXR cascade in insomnia and sleep deprivation link Alzheimer's disease and Parkinson's disease: Therapeutic avenue of Dual OXR Antagonist (DORA).

Sleep plays a role in the elimination of neurotoxic metabolites that are accumulated in the waking brain as a result of neuronal activity. Long-term insomnia and sleep deprivation are associated with oxidative stress, neuroinflammation, amyloid beta (Aβ) deposition, and Lewy body formation, which are known to increase the risk of mild cognitive impairment (MCI) and dementia. Orexin A (OXA) and orexin B (OXB), two neuropeptides produced in the lateral hypothalamus, are known to influence the sleep-wake cycle and the stress responses through their interactions with OX receptor 1 (OX1R) and OX receptor 2 (OX2R), respectively. OX/OXR cascade demonstrates intricate neuroprotective and anti-inflammatory effects by inhibiting nuclear factor-kappa B (NF-kB) and PLC/Ca2+ pathway activation. OX1R binds OXA more strongly than OXB by one-order ratio, whereas OX2R binds both OXA and OXB with equal strengths. Overexpression of OXs in individuals experiences sleep deprivation, circadian rhythm disturbances, insomnia-associated MCI, Parkinson's disease (PD), and Alzheimer's disease (AD). Many dual OXR antagonists (DORAs) have been effective in their clinical studies, with suvorexant and daridorexant receiving FDA clearance for insomnia therapy in 2014 and 2022 respectively. The results of clinical studies suggested that there is a new pharmaceutical option for treating insomnia and the sleep deprivation-AD/PD relationship by targeting the OXR system. DORAs treatment reduces Aβ deposition in the brain and improves synaptic plasticity and circadian expression. This review indicates the link between sleep disorders and MCI, DORAs are an appropriate medication category for treating insomnia, and sleep deprivation links AD and PD.

Comparing the Effectiveness of Cannabis to Treat Sleep Impairments between Those With and Without Sleep Disorders

Comparing the Effectiveness of Cannabis to Treat Sleep Impairments between Those With and Without Sleep Disorders

Insomnia and sleep apnea in the entire population of US Army soldiers: Associations with deployment and combat exposure 2010-2019, a retrospective cohort investigation

This retrospective cohort study examined clinically diagnosed insomnia and sleep apnea and analyzed associations with deployment and combat exposure in active-duty soldiers (n=1,228,346) from 2010 to 2019. Retrospective data were obtained from the Soldier Performance, Health, and Readiness database. Overseas soldier deployments peaked in 2010, decreasing thereafter as soldiers were withdrawn from Iraq and Afghanistan. From 2010 to 2012 insomnia incidence increased at a rate of 6.7 cases/1000 soldier-years, then decreased after 2012 at 5.3 cases/1000 soldier-years. Sleep apnea increased 2010-2016 at 1.9 cases/1000 soldier-years and generally declined thereafter. Risk of insomnia increased with deployment (hazard ratio=1.51; 95% confidence interval=1.49-1.52) and combat exposure (hazard ratio=1.15; 95% confidence interval=1.13-1.17). Risk of sleep apnea was increased by deployment (hazard ratio=1.89; 95% confidence interval, 1.86-1.92) and combat exposure (hazard ratio=1.09; 95% confidence interval, 1.07-1.11). Most relationships remained after accounting for other factors in multivariable analyses, except that the association between sleep apnea and combat exposure was reduced (hazard ratio=0.94; 95% confidence interval=0.92-0.97). Insomnia risk decreased in the period nearly in parallel with a reduction in the number of deployments; nonetheless deployment and combat exposure increased insomnia risk in the period examined. Risk of sleep apnea increased in the period and was related to deployment but not combat exposure after accounting for demographics and comorbid conditions. Despite reductions in insomnia incidence and a slowing in sleep apnea incidence, sleep disorders remain highly prevalent, warranting continued emphasis on sleep-disorder screening and improving the soldier sleep habits.

Abstract WMP97: Glymphatic Dysfunction as a Link Between Cerebral Small Vessel Disease, Sleep Disorders, and Cognitive Decline: Insights from a Longitudinal Community Cohort Study

Abstract WMP97: Glymphatic Dysfunction as a Link Between Cerebral Small Vessel Disease, Sleep Disorders, and Cognitive Decline: Insights from a Longitudinal Community Cohort Study

Prevalence and factor associated with depressive symptoms in patients with osteoarthritis: A cross-sectional study.

Osteoarthritis (OA) is a prevalent degenerative joint condition. Among OA patients, depressive symptoms are the most frequent psychiatric disorder, negatively impacting both prognosis and quality of life. This study analyzed the independent factors associated with the development of depressive symptoms in patients with OA and constructed a nomogram to assess the risk of developing depressive symptoms. An analysis was conducted on data from 2093 OA patients in the NHANES database, covering 2007 to 2014. A training set and a validation set were randomly assigned to participants in a 7:3 ratio. Variables significantly associated with depressive symptoms in OA patients were identified using the least absolute shrinkage and selection operator (LASSO) and multivariable logistic regression analyses and nomograms were constructed. Its performance and clinical relevance were assessed using receiver operating characteristic (ROC) curves, C indices, calibration curves, and decision curves. Among the 2093 OA patients, 357 were assessed as having depressive symptoms. There are eight independent relevant factors, which are gender, age, poverty-to-income ratio (PIR), race, educational attainment, smoking status, diabetes, and sleep disorder. The AUC values of the training and validation sets were 0.718 (95%CI: 0.683-0.752) and 0.733 (95%CI: 0.678-0.788). Calibration and decision curve analyses showed that this nomogram exhibits high accuracy, good discrimination, and potential clinical benefits on both training and validation sets. We screened to obtain factors associated with depressive symptoms in patients with OA. Dynamic nomograms enable the combination of individual relevant factors for better assessing and managing high-risk OA groups.

Long-Term Insomnia Treatment with Benzodiazepines and Alzheimer’s Disease: A Systematic Review

Alzheimer’s disease is the most common form of dementia. Benzodiazepines are the most widely used pharmacological class in the treatment of insomnia and other sleep disorders. Some literature suggests that the chronic use of benzodiazepines is associated with the development of cognitive decline. This review aims to evaluate the use of benzodiazepines and its association with the development of Alzheimer’s disease. A systematic review of the literature was carried out using the MEDLINE and Embase databases. Protocols followed the PRISMA-P 2020 methodology, and, after the analysis of the included studies, a narrative synthesis of the results was carried out. Only two cohort studies were identified that met defined eligibility criteria. In the retrospective study, a significant risk of developing Alzheimer’s disease after treatment with benzodiazepines was found. In the prospective study, the prevalence of Alzheimer’s disease was not associated with treatment with benzodiazepines. Results suggest that only the largest study presented a significant risk of developing Alzheimer’s disease. Given the scarce scientific evidence found, it is concluded that further research on this topic is necessary.

Sleep deprivation activated AMPK/FOXO3a signaling mediates pineal autophagy impairment to reduce melatonin secretion in CUMS+SD rats leading to depression combined with insomnia.

This study established an animal model of comorbid depression and insomnia by combining chronic unpredictable mild stress (CUMS) with sleep deprivation (SD). The pathogenesis of comorbid depression and insomnia may be associated with impaired AMPK/FOXO3a signaling, which mediates autophagy inhibition, leading to decreased pineal melatonin secretion. The findings revealed that CUMS+SD rats exhibited more pronounced depression-like behaviors, sleep disorders, increased central oxidative stress, and exacerbated neuroinflammation, accompanied by reduced levels of 5-hydroxytryptophan (5-HT) and melatonin in the pineal gland. Notably, further investigations revealed that impaired mitochondrial autophagy in the pineal gland is closely linked to the significant suppression of AMPK/FOXO3a signaling. The combined intervention of venlafaxine and melatonin effectively ameliorated the impaired mitochondrial autophagy in the pineal gland of CUMS+SD rats and stimulated melatonin secretion. Consequently, the study proposes that dysfunctional mitochondrial autophagy regulated by the AMPK/FOXO3a pathway can influence melatonin secretion, thereby playing a pivotal role in the pathogenesis of depression combined with insomnia.