RESUMEN
Emotion processing abnormalities and sleep pathology are central to the phenomenology of paediatric posttraumatic stress disorder, and sleep disturbance has been linked to the development, maintenance and severity of the disorder. Given emerging evidence indicating a role for sleep in emotional brain function, it has been proposed that dysfunctional processing of emotional experiences during sleep may play a significant role in affective disorders, including posttraumatic stress disorder. Here we sought to examine the relationship between sleep and emotion processing in typically developing youth, and youth with a diagnosis of posttraumatic stress disorder . We use high-density electroencephalogram to compare baseline sleep with sleep following performance on a task designed to assess both memory for and reactivity to negative and neutral imagery in 10 youths with posttraumatic stress disorder, and 10 age- and sex-matched non-traumatized typically developing youths. Subjective ratings of arousal to negative imagery (ΔArousal = post-sleep minus pre-sleep arousal ratings) remain unchanged in youth with posttraumatic stress disorder following sleep (mean increase 0.15, CI -0.28 to +0.58), but decreased in TD youth (mean decrease -1.0, 95% CI -1.44 to -0.58). ΔArousal, or affective habituation, was negatively correlated with global change in slow-wave activity power (ρ = -0.58, p = .008). When considered topographically, the correlation between Δslow-wave activity power and affective habituation was most significant in a frontal cluster of 27 electrodes (Spearman, ρ = -0.51, p = .021). Our results highlight the importance of slow-wave sleep for adaptive emotional processing in youth, and have implications for symptom persistence in paediatric posttraumatic stress disorder. Impairments in slow-wave activity may represent a modifiable risk factor in paediatric posttraumatic stress disorder.
Asunto(s)
Emociones , Sueño , Trastornos por Estrés Postraumático/fisiopatología , Trastornos por Estrés Postraumático/psicología , Adolescente , Niño , Femenino , Humanos , Masculino , Proyectos PilotoRESUMEN
Although mandibular advancement device (MAD) treatment of adults with obstructive sleep apnea (OSA) is generally less efficacious than positive airway pressure (PAP), the two treatments are associated, with similar clinical outcomes. As a sub-analysis of a randomized trial comparing the effect of MAD versus PAP on blood pressure, this study compared objectively measured adherence to MAD versus PAP treatment in adults with OSA. Adults with OSA (age 54.1 ± 11.2 [standard deviation] years, 71.1% male, apnea-hypopnea index 31.6 ± 22.7 events/h) were randomized to MAD (n = 89) or PAP (n = 91) treatment for 3-6 months. Objective adherence was assessed with a thermal sensor embedded in the MAD and a pressure sensor in the PAP unit. In a per protocol analysis, no difference was observed in average daily hours of use over all days in participants on MAD (n = 35, 4.4 ± 2.9 h) versus PAP (n = 51, 4.7 ± 1.6 h, p = .597) treatment when days with missing adherence data were included as no use. MAD was used on a lower percentage of days (62.5 ± 36.4% versus 79.9 ± 19.8%, p = .047), but with greater average daily hours of use on days used (6.4 ± 1.9 h versus 5.7 ± 1.2 h, p = .013). Average daily hours of use in the first week were associated with long-term adherence to MAD (p < .0001) and PAP (p = .0009) treatment. Similar results were obtained when excluding days with missing adherence data. In conclusion, no significant difference was observed in objectively measured average daily hours of MAD and PAP adherence in adults with OSA, despite differences in the patterns of use. MAD adherence in the first week predicted long-term use.
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Presión de las Vías Aéreas Positiva Contínua , Avance Mandibular , Cooperación del Paciente , Apnea Obstructiva del Sueño/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ferulas Oclusales , Resultado del TratamientoRESUMEN
OBJECTIVES: Information is lacking regarding how commonly unblinding of treatment assignment occurs in hypnotic randomized clinic trials (RCTs). We now report the "best guesses" of clinical trial participants, versus study coordinators, versus study physicians in the study Reducing Suicidal Ideation Through Insomnia Treatment (REST-IT). METHODS: REST-IT, a, 8-week double-blind RCT, compared zolpidem extended-release (ER) versus placebo at bedtime in 103 adults with major depressive disorder with insomnia and suicidal ideation, and who received open label selective serotonin reuptake inhibitors. At the conclusion of study participation, 89 of the participants in this study, the study coordinators, and the study physicians each independently recorded their "best guess" of the treatment assigned. RESULTS: Patients guessed correctly 58.4% of the time, coordinators 53.9% of the time, and physicians 49.4% of the time, and none were different from chance alone. Agreement between patient/coordinator, patient/doctor, and coordinator/doctor dyads were 75%-78% with no significant differences in agreement between the dyads. CONCLUSIONS: "Best guesses" of all parties were not different from chance, suggesting that the blind was maintained and that assessment bias was minimized in this RCT of zolpidem ER versus placebo. Our results may not apply to other hypnotics or other RCT designs.
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Trastorno Depresivo Mayor/complicaciones , Hipnóticos y Sedantes/uso terapéutico , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Prevención del Suicidio , Zolpidem/uso terapéutico , Adolescente , Adulto , Sesgo , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/psicología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Trastornos del Inicio y del Mantenimiento del Sueño/psicología , Ideación Suicida , Suicidio/psicología , Adulto JovenRESUMEN
Sleep apnea is a condition with significant health risks and increased risk of mortality and is prevalent in patients with chronic kidney disease. This paper describes the detrimental cardiovascular sequelae of sleep-disordered breathing and explores the bidirectional relationship between chronic kidney disease and obstructive sleep apnea. Obstructive sleep apnea-related hypoxia produces a range of harmful systemic effects including oxidative stress, inflammation, and sympathetic activation that collectively worsen the progression of renal disease. In turn, chronic kidney disease can result in increased severity of sleep apnea through inducing (1) uremic neuropathy and myopathy, (2) altered chemosensitivity, and (3) hypervolemia. Continuous positive airway pressure therapy remains the mainstay of treatment for reversing the health risks of apnea. Other strategies aimed at decreasing the high prevalence and associated morbidity of sleep apnea include weight loss, oral appliances, and corrective surgery in the case of airway obstruction.
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Riñón/fisiopatología , Pulmón/fisiopatología , Insuficiencia Renal Crónica/fisiopatología , Respiración , Apnea Obstructiva del Sueño/fisiopatología , Sueño , Presión de las Vías Aéreas Positiva Contínua , Femenino , Humanos , Masculino , Avance Mandibular/instrumentación , Aparatos Ortodóncicos , Pronóstico , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapia , Medición de Riesgo , Factores de Riesgo , Conducta de Reducción del Riesgo , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/terapiaRESUMEN
The objective of the study was to determine if sleep disorder, depression or anxiety screening status was associated with safety outcomes in a diverse population of hospital workers. A sample of shift workers at four hospitals participated in a prospective cohort study. Participants were screened for five sleep disorders, depression and anxiety at baseline, then completed prospective monthly surveys for the next 6 months to capture motor vehicle crashes, near-miss crashes, occupational exposures and medical errors. We tested the associations between sleep disorders, depression and anxiety and adverse safety outcomes using incidence rate ratios adjusted for potentially confounding factors in a multivariable negative binomial regression model. Of the 416 hospital workers who participated, two in five (40.9%) screened positive for a sleep disorder and 21.6% screened positive for depression or anxiety. After multivariable adjustment, screening positive for a sleep disorder was associated with 83% increased incidence of adverse safety outcomes. Screening positive for depression or anxiety increased the risk by 63%. Sleep disorders and mood disorders were independently associated with adverse outcomes and contributed additively to risk. Our findings suggest that screening for sleep disorders and mental health screening can help identify individuals who are vulnerable to adverse safety outcomes. Future research should evaluate sleep and mental health screening, evaluation and treatment programmes that may improve safety.
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Ansiedad/epidemiología , Depresión/epidemiología , Personal de Salud/normas , Horario de Trabajo por Turnos/efectos adversos , Trastornos del Sueño-Vigilia/epidemiología , Accidentes de Tránsito/prevención & control , Accidentes de Tránsito/psicología , Adulto , Ansiedad/diagnóstico , Ansiedad/psicología , Estudios de Cohortes , Depresión/diagnóstico , Depresión/psicología , Femenino , Personal de Salud/psicología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Horario de Trabajo por Turnos/psicología , Trastornos del Sueño-Vigilia/diagnóstico , Trastornos del Sueño-Vigilia/psicología , Encuestas y CuestionariosRESUMEN
OBJECTIVE: Depression is often associated with disruptions in sleep and circadian rhythms. We aimed to confirm these relationships via actigraphic assessment in a large, population-based sample and test whether sex moderates these relationships. METHODS: A total of 418 participants (age = 35-85 years, mean [standard deviation] = 57.04 [11.47]) completed questionnaires and 1 week of actigraphy, used to calculate sleep and rest-activity statistics including mesor (mean activity level), amplitude (height of rhythm), and acrophase (time of day that rhythm peaks). RESULTS: Depressive symptoms, assessed via Center for Epidemiologic Studies Depression Scale, were associated with disrupted sleep and rest-activity rhythms. Furthermore, men demonstrated longer sleep onset latency (SOL, B = -13.28, p < .001), longer wake time after sleep onset (B = -6.26, p < .01), lower sleep efficiency (B = 5.91, p < .001), and lower total sleep time (TST, B = 33.16, p < .001) than women. Sex moderated the relationship between depression and SOL, TST, mesor, and amplitude; sex-stratified models revealed that higher depression scores were associated with greater SOL (B = 1.05, p < .001) and less TST (B = -0.87, p < .10) for women with higher depressive symptoms, but lower mesor (B = -1.75, p < .01) and amplitude (B = -1.94, p < .01) for men with higher depressive symptoms. CONCLUSIONS: Depressive symptoms were related to disrupted sleep continuity and rest-activity rhythms in this population-based sample; however, these relationships differed by sex. Women with greater depressive symptoms exhibited difficulty with sleep continuity, whereas men with greater depressive symptoms demonstrated disruption throughout the 24-hour rhythm.
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Actigrafía , Depresión/epidemiología , Trastornos del Sueño del Ritmo Circadiano/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Depresión/complicaciones , Depresión/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Factores Sexuales , Trastornos del Sueño del Ritmo Circadiano/etiología , Trastornos del Sueño del Ritmo Circadiano/psicología , Encuestas y CuestionariosRESUMEN
OBJECTIVE: Suvorexant is an orexin receptor antagonist approved for treating insomnia at doses of 10-20 mg. Previously reported phase III results showed that suvorexant was effective and well-tolerated in a combined-age population (elderly and nonelderly adults). The present analysis evaluated the clinical profile of suvorexant specifically in the elderly. METHODS: Prespecified subgroup analyses of pooled 3-month data from two (efficacy) and three (safety) randomized, double-blind, placebo-controlled, parallel-group trials. In each trial, elderly (≥65 years) patients with insomnia were randomized to suvorexant 30 mg, suvorexant 15 mg, and placebo. By design, fewer patients were randomized to 15 mg. Patient-reported and polysomnographic (subset of patients) sleep maintenance and onset endpoints were measured. RESULTS: Suvorexant 30 mg (N = 319) was effective compared with placebo (N = 318) on patient-reported and polysomnographic sleep maintenance, and onset endpoints at Night 1 (polysomnographic endpoints)/Week 1 (patient-reported endpoints), Month 1, and Month 3. Suvorexant 15 mg (N = 202 treated) was also effective across these measures, although the onset effect was less evident at later time points. The percentages of patients discontinuing because of adverse events over 3 months were 6.4% for 30 mg (N = 627 treated), 3.5% for 15 mg (N = 202 treated), and 5.5% for placebo (N = 469 treated). Somnolence was the most common adverse event (8.8% for 30 mg, 5.4% for 15 mg, 3.2% for placebo). CONCLUSION: Suvorexant generally improved sleep maintenance and onset over 3 months of nightly treatment and was well-tolerated in elderly patients with insomnia (clinicaltrials.gov; NCT01097616, NCT01097629, NCT01021813).
Asunto(s)
Azepinas/uso terapéutico , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Triazoles/uso terapéutico , Anciano , Azepinas/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , Metaanálisis como Asunto , Polisomnografía , Fármacos Inductores del Sueño/uso terapéutico , Triazoles/efectos adversosRESUMEN
BACKGROUND: Lung transplant recipients are at high risk of developing sleep disorders such as insomnia, but the prevalence and features are currently poorly characterized within this population. Since these disorders are associated with increased morbidity and mortality, it is important to identify them to optimize the care of lung transplant recipients. We sought to evaluate the prevalence of insomnia within our university-based lung transplant clinic and determine whether a relationship exists between insomnia and exposure to immunosuppressant medications following transplantation. METHODS: Participants were recruited through the University of Wisconsin Hospital and Clinics Lung Transplant Clinic (N = 125). Participants (n = 92) completed the adult sleep history questionnaire, which included the Insomnia Severity Index (ISI) to assess for insomnia (defined as ISI score >10). Cumulative tacrolimus exposure was determined in 73 patients by performing an area under the curve calculation to assess for a potential relationship between tacrolimus exposure and insomnia. RESULTS: The prevalence of insomnia was 40% within this population. Although no difference in time since transplant was found, cumulative mean ± standard error of the mean tacrolimus exposure was significantly higher in patients with insomnia versus those without insomnia (17 190 ± 1673 ng·d/mL vs 12 130 ± 1630 ng·d/mL, respectively; P = .04). Estimated tacrolimus exposure was not greater with increasing frequency of insomnia complaints (analysis of variance P = .54). CONCLUSION: In our population, insomnia is common after lung transplantation, with prevalence greater than the general population. Higher cumulative exposure to tacrolimus may contribute to insomnia in this group. Future research should investigate the relationship between immunosuppressant therapy and development of sleep disorders.
Asunto(s)
Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Trasplante de Pulmón , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Tacrolimus/uso terapéutico , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Wisconsin/epidemiologíaRESUMEN
Learning leads to rapid microstructural changes in gray (GM) and white (WM) matter. Do these changes continue to accumulate if task training continues, and can they be reverted by sleep? We addressed these questions by combining structural and diffusion weighted MRI and high-density EEG in 16 subjects studied during the physiological sleep/wake cycle, after 12 h and 24 h of intense practice in two different tasks, and after post-training sleep. Compared to baseline wake, 12 h of training led to a decline in cortical mean diffusivity. The decrease became even more significant after 24 h of task practice combined with sleep deprivation. Prolonged practice also resulted in decreased ventricular volume and increased GM and WM subcortical volumes. All changes reverted after recovery sleep. Moreover, these structural alterations predicted cognitive performance at the individual level, suggesting that sleep's ability to counteract performance deficits is linked to its effects on the brain microstructure. The cellular mechanisms that account for the structural effects of sleep are unknown, but they may be linked to its role in promoting the production of cerebrospinal fluid and the decrease in synapse size and strength, as well as to its recently discovered ability to enhance the extracellular space and the clearance of brain metabolites.
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Encéfalo/fisiopatología , Aprendizaje/fisiología , Privación de Sueño/fisiopatología , Sueño/fisiología , Vigilia , Imagen de Difusión por Resonancia Magnética , Electroencefalografía , Femenino , Sustancia Gris/fisiopatología , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Sustancia Blanca/fisiopatología , Adulto JovenRESUMEN
CONTEXT: Complications following lung transplantation are common and significantly reduce quality of life, and increase morbidity and mortality. Increasing evidence suggests sleep disorders are prevalent following lung transplantation, but factors associated with their development are not known. OBJECTIVES: We sought to evaluate the prevalence of restless legs syndrome (RLS) in a lung transplant population and determine if a relationship exists between RLS and exposure to immunosuppressant medications. DESIGN, SETTING, AND PARTICIPANTS: Subjects were recruited through the University of Wisconsin Hospital and Clinics Lung Transplant Clinic (N = 125). Participants (N = 81) completed sleep questionnaires, including the four RLS diagnostic criteria, insomnia severity index, and Sheehan disability scale. Cumulative tacrolimus exposure was determined in 62 subjects by calculating an area under the curve (AUC) to assess for a relationship with restless legs syndrome. RESULTS: Prevalence of RLS was 35 percent. Cumulative mean ± SEM tacrolimus exposure was similar in patients with RLS versus those without RLS (17446 ± 1855 ng days/mL vs. 15303 ± 1643 ng days/mL, respectively; p = 0.42). Insomnia severity index scores (12.5 ± 1.0 vs 6.8 ± 0.7, p < 0.0001) and Sheehan disability scores (7.8 ± 1.3 vs 3.6 ± 0.6, p = 0.003) were significantly higher in those with vs those without RLS symptoms, respectively. CONCLUSIONS: Our data confirms increased prevalence of RLS following lung transplantation reported by previous studies. RLS symptoms were not related to estimated tacrolimus exposure. Predictors of RLS following lung transplantation need to be further investigated to better identify and control RLS symptoms and reduce associated insomnia and disability.
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Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Trasplante de Pulmón/estadística & datos numéricos , Síndrome de las Piernas Inquietas/epidemiología , Tacrolimus/uso terapéutico , Área Bajo la Curva , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To investigate (1) circadian rest-activity rhythm disturbances among endometrial cancer patients as they recover from surgery in comparison to a historical reference group of women with no cancer history and (2) health- and treatment-related predictors of dysregulated rest-activity rhythms in endometrial cancer patients. METHODS: 60 endometrial cancer patients participated in a prospective, longitudinal study with actigraphic assessment at 1week, 1month, and 4months post-surgery. 60 women without cancer from an epidemiological sample completed one actigraphic assessment, acting as a reference group. RESULTS: On average, results revealed initial significant rest-activity dysregulation at 1week and 1month post-surgery for the endometrial cancer group and then significant recovery in rest-activity patterns at 4months post-surgery. Similarly, the cancer group had significantly more impaired rhythms than the reference group at 1week post-surgery, but demonstrated comparable rhythms by 4months post-surgery. Among the health- and treatment-related variables examined, obesity and receipt of more invasive surgery were found to predict more impaired rhythms at all time points. CONCLUSION(S): The current study highlights significant disturbances in rest-activity patterns for endometrial cancer patients initially during surgical recovery followed by improvement in these patterns by 4months post-surgery; however, obese patients and those having more invasive surgery demonstrated more impaired rest-activity patterns throughout the 4-month recovery period. Further research is warranted to understand how more impaired rest-activity patterns relate to health and quality of life outcomes.
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Ritmo Circadiano/fisiología , Neoplasias Endometriales/fisiopatología , Neoplasias Endometriales/cirugía , Actigrafía/métodos , Femenino , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND/AIMS: Suicide is a major public health concern, yet there are very few randomized clinical trials that have been conducted to reduce suicidal ideation in patients at risk of suicide. We describe the rationale and refinements of such a trial that is designed to assess the effect of a hypnotic medication on suicidal ideation in adult outpatients currently experiencing suicidal ideation. METHODS: "Reducing Suicidal Ideation Through Insomnia Treatment" is a multi-site randomized clinical trial that includes three recruiting sites and one data management site. This 4-year study is in its second year of recruitment. The purpose of the study is to compare hypnotic medication versus placebo as an add-on treatment to a selective serotonin reuptake inhibitor as a means of reducing suicidal ideation in depressed adult outpatients with insomnia and suicidal ideation. The safety features of the study follow the 2001 National Institutes of Health guidelines for studies that include patients at risk of suicide. RESULTS: In total, 584 potential participants have undergone telephone screening; 67% of these failed the phone screen, most often due to an absence of expressed suicidal ideation (26% of the telephone screen fails). A total of 115 people appeared for a face-to-face baseline assessment, and 40 of these had completed a taper off of their ineffective psychotropic medications before the baseline assessments. In all, 64% of those who completed baseline assessments failed to proceed to randomization, most commonly because of no clinically significant suicidal ideation (51% of those excluded at baseline). One participant was offered and accepted voluntary psychiatric hospitalization in lieu of study participation. Thus far, 40 participants have been randomized into the study and 88.7% of scheduled visits have been attended, with 93.8% adherence to the selective serotonin reuptake inhibitor and 91.6% adherence to the randomized hypnotic versus placebo. None of the randomized participants have required hospitalization or had a suicide attempt. CONCLUSION: By carefully considering the inclusion and exclusion criteria and other safety features, the safe conduct of randomized clinical trials in suicidal adult patients is possible, including the inclusion of participants who have undergone a prescribed tapering off of psychotropic medications prior to baseline assessment.
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Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/tratamiento farmacológico , Hipnóticos y Sedantes/uso terapéutico , Proyectos de Investigación , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Ideación Suicida , Adulto , Quimioterapia Combinada , Femenino , Humanos , Hipnóticos y Sedantes/administración & dosificación , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Selección de Paciente , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Factores Socioeconómicos , Estados UnidosRESUMEN
Alzheimer's disease (AD) is a neurodegenerative disorder affecting nearly one in nine older adults in the US. This number is expected to grow exponentially, thereby increasing stress on caregivers and health systems. While some risk factors for developing AD are genetic, an estimated 1/3 of AD cases are attributed to lifestyle. Many of these risk factors emerge decades before clinical symptoms of AD are detected, and targeting them may offer more efficacious strategies for slowing or preventing disease progression. This review will focus on two common risk factors for AD, metabolic dysfunction and sleep impairments, and discuss potential mechanisms underlying their relationship to AD pathophysiology. Both sleep and metabolism can alter AD-related protein production and clearance, contributing to an imbalance that drives AD progression. Additionally, these risk factors have bidirectional relationships with AD, where the presence of AD-related pathology can further disrupt sleep and worsen metabolic functioning. Sleep and metabolism also appear to have a bidirectional relationship with each other, indirectly exacerbating AD pathophysiology. Understanding the mechanisms involved in these relationships is critical for identifying new strategies to slow the AD cascade.
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Enfermedad de Alzheimer , Humanos , Anciano , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Sueño , Emociones , Factores de RiesgoRESUMEN
BACKGROUND: There are limited data regarding gamma-aminobutyric acid (GABA) allosteric modulator sleep-aid medications in persons with depression, insomnia, and suicidal ideation (SI). AIMS: This secondary analysis examined the relationship of age to insomnia and the impact of age on the treatment of insomnia with zolpidem extended-release (zolpidem-ER) in depressed suicidal patients. A prior report found that the addition of zolpidem-ER promoted significantly superior reductions in global severity of insomnia in depressed outpatients with insomnia and SI over 8 weeks, but here we report the differences among early, middle, and late insomnia. METHODS: This secondary analysis examined the three early, middle, and late insomnia items of the Hamilton Rating Scale for Depression (HRSD) and their relationship to age and responsiveness to treatment with zolpidem-ER. One hundred and three patients with major depression, SI, and insomnia received open-label serotonin reuptake inhibitors and were randomly allocated 1:1 to receive zolpidem-ER or placebo at bedtime. Results: Older age at baseline was associated with worse middle and late insomnia, but not with early insomnia. Subsequent treatment with zolpidem-ER produced superior improvement in early and middle insomnia, but not late insomnia. CONCLUSIONS: These findings are consistent with the known age-related advancement of sleep timing in the general population and depressed outpatients and with the expected effects of a short half-life GABA allosteric modulator sleep aid. By implication, prescribers of pharmacologic treatment of insomnia in depressed patients should consider an alternative to zolpidem-ER when late insomnia is a concern.Trial registration number: ClinicalTrials.gov Identifier: NCT01689909.
RESUMEN
Background: While obstructive sleep apnea (OSA) and insomnia symptoms in neurotypical populations are associated with Alzheimer's disease (AD), their association with dementia in adults with Down syndrome (DS) remains less clear, even though these symptoms are prevalent and treatable in DS. Understanding their associations with AD-related dementia status, cognitive impairment, and functional deterioration may lead to interventions to slow decline or disease progression in adults with DS. Objective: To characterize differences in OSA and insomnia symptom expression by dementia status, and to determine which sleep factors support dementia diagnosis. Methods: Multimodal consensus conference was used to determine dementia status in 52 adults with DS (52.2â±â6.4 years, 21 women). Cognitive impairment, adaptive behavior skills, and symptoms of OSA and insomnia were quantified using validated assessments for adults with DS and their primary informants. Results: A sex by dementia status interaction demonstrated that older women with DS and dementia had more severe terminal insomnia but not OSA symptoms relative to older women with DS who were cognitively stable (CS). Greater insomnia symptom severity was associated with greater functional impairments in social and self-care domains adjusting for age, sex, premorbid intellectual impairment, and dementia status. Conclusions: Insomnia symptoms are more severe in women with DS with dementia than in women with DS and no dementia, and regardless of dementia status or sex, more severe insomnia symptoms are associated with greater impairment in activities of daily living. These findings underscore the potential importance of early insomnia symptom evaluation and treatment in women with DS at risk of developing AD.
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Enfermedad de Alzheimer , Demencia , Síndrome de Down , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Femenino , Síndrome de Down/complicaciones , Síndrome de Down/epidemiología , Masculino , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/epidemiología , Persona de Mediana Edad , Demencia/epidemiología , Adulto , Progresión de la Enfermedad , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/complicaciones , Pruebas Neuropsicológicas , Disfunción Cognitiva/epidemiologíaRESUMEN
Although cardiorespiratory fitness (CRF), an important marker of youth health, is associated with earlier sleep/wake schedule, its relationship with circadian rhythms is unclear. This study examined the associations between CRF and rhythm variables in adolescents. Eighteen healthy adolescents (10 females and 8 males; Mage = 14.6 ± 2.3 yr) completed two study visits on weekdays bracketing an ambulatory assessment during summer vacation. Visit 1 included in-laboratory CRF assessment (peak VÌo2) using a ramp-type progressive cycle ergometry protocol and gas exchange measurement, which was followed by 7-14 days of actigraphy to assess sleep/wake patterns and 24-h activity rhythms. During Visit 2, chronotype, social jetlag (i.e., the difference in midsleep time between weekdays and weekends), and phase preference were assessed using a questionnaire, and hourly saliva samples were collected to determine the dim light melatonin onset (DLMO) phase. All analyses were adjusted for sex, pubertal status, and physical activity. Greater peak VÌo2 was associated with earlier sleep/wake times and circadian phase measures, including acrophase, UP time, DOWN time, last activity peak (LAP) time, and chronotype (all P < 0.05). Peak VÌo2 was negatively associated with social jetlag (P = 0.02). In addition, the mixed-model analysis revealed a significant interaction effect between peak VÌo2 and actigraphy-estimated hour-by-hour activity patterns (P < 0.001), with the strongest effects observed at around the time of waking (0600-1000). In healthy adolescents, better CRF was associated with an earlier circadian phase and increased activity levels notably during the morning. Future studies are needed to investigate the longitudinal effects of the interactions between CRF and advanced rhythms on health outcomes.NEW & NOTEWORTHY In healthy adolescents, better cardiorespiratory fitness, as assessed by the gold standard measure [laboratory-based assessment of peak oxygen consumption (VÌo2)], was associated with earlier circadian timing of sleep/wake patterns, rest-activity rhythms and chronotype, and less social jetlag. These findings highlight the close interrelationships between fitness and rhythms and raise the possibility that maintaining higher cardiorespiratory fitness levels alongside earlier sleep/wake schedule and activity rhythms may be important behavioral intervention targets to promote health in adolescents.
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Capacidad Cardiovascular , Masculino , Femenino , Adolescente , Humanos , Niño , Proyectos Piloto , Promoción de la Salud , Ritmo Circadiano , SueñoRESUMEN
Obstructive sleep apnea (OSA) is common in older adults and is associated with medial temporal lobe (MTL) degeneration and memory decline in aging and Alzheimer's disease (AD). However, the underlying mechanisms linking OSA to MTL degeneration and impaired memory remains unclear. By combining magnetic resonance imaging (MRI) assessments of cerebrovascular pathology and MTL structure with clinical polysomnography and assessment of overnight emotional memory retention in older adults at risk for AD, cerebrovascular pathology in fronto-parietal brain regions was shown to statistically mediate the relationship between OSA-related hypoxemia, particularly during rapid eye movement (REM) sleep, and entorhinal cortical thickness. Reduced entorhinal cortical thickness was, in turn, associated with impaired overnight retention in mnemonic discrimination ability across emotional valences for high similarity lures. These findings identify cerebrovascular pathology as a contributing mechanism linking hypoxemia to MTL degeneration and impaired sleep-dependent memory in older adults.
RESUMEN
BACKGROUND: Obstructive sleep apnea (OSA) increases risk for cognitive decline and Alzheimer's disease (AD). While the underlying mechanisms remain unclear, hypoxemia during OSA has been implicated in cognitive impairment. OSA during rapid eye movement (REM) sleep is usually more severe than in non-rapid eye movement (NREM) sleep, but the relative effect of oxyhemoglobin desaturation during REM versus NREM sleep on memory is not completely characterized. Here, we examined the impact of OSA, as well as the moderating effects of AD risk factors, on verbal memory in a sample of middle-aged and older adults with heightened AD risk. METHODS: Eighty-one adults (mean age:61.7 ± 6.0 years, 62% females, 32% apolipoprotein E ε4 allele (APOE4) carriers, and 70% with parental history of AD) underwent clinical polysomnography including assessment of OSA. OSA features were derived in total, NREM, and REM sleep. REM-NREM ratios of OSA features were also calculated. Verbal memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT). Multiple regression models evaluated the relationships between OSA features and RAVLT scores while adjusting for sex, age, time between assessments, education years, body mass index (BMI), and APOE4 status or parental history of AD. The significant main effects of OSA features on RAVLT performance and the moderating effects of AD risk factors (i.e., sex, age, APOE4 status, and parental history of AD) were examined. RESULTS: Apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxyhemoglobin desaturation index (ODI) during REM sleep were negatively associated with RAVLT total learning and long-delay recall. Further, greater REM-NREM ratios of AHI, RDI, and ODI (i.e., more events in REM than NREM) were related to worse total learning and recall. We found specifically that the negative association between REM ODI and total learning was driven by adults 60 + years old. In addition, the negative relationships between REM-NREM ODI ratio and total learning, and REM-NREM RDI ratio and long-delay recall were driven by APOE4 carriers. CONCLUSION: Greater OSA severity, particularly during REM sleep, negatively affects verbal memory, especially for people with greater AD risk. These findings underscore the potential importance of proactive screening and treatment of REM OSA even if overall AHI appears low.
Asunto(s)
Enfermedad de Alzheimer , Polisomnografía , Apnea Obstructiva del Sueño , Sueño REM , Humanos , Femenino , Masculino , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/complicaciones , Persona de Mediana Edad , Sueño REM/fisiología , Anciano , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/fisiopatología , Apnea Obstructiva del Sueño/genética , Factores de Riesgo , Aprendizaje Verbal/fisiología , Apolipoproteína E4/genética , Memoria/fisiología , Índice de Severidad de la Enfermedad , Síndromes de la Apnea del Sueño/complicaciones , Síndromes de la Apnea del Sueño/fisiopatología , Síndromes de la Apnea del Sueño/genéticaRESUMEN
Insomnia is a prevalent complaint in clinical practice that can present independently or comorbidly with another medical or psychiatric disorder. In either case, it might need treatment of its own. Of the different therapeutic options available, benzodiazepine-receptor agonists (BzRAs) and cognitive-behavioural therapy (CBT) are supported by the best empirical evidence. BzRAs are readily available and effective in the short-term management of insomnia, but evidence of long-term efficacy is scarce and most hypnotic drugs are associated with potential adverse effects. CBT is an effective alternative for chronic insomnia. Although more time consuming than drug management, CBT produces sleep improvements that are sustained over time, and this therapy is accepted by patients. Although CBT is not readily available in most clinical settings, access and delivery can be made easier through use of innovative methods such as telephone consultations, group therapy, and self-help approaches. Combined CBT and drug treatment can optimise outcomes, although evidence to guide clinical practice on the best way to integrate these approaches is scarce.
Asunto(s)
Terapia Cognitivo-Conductual , Agonistas de Receptores de GABA-A/uso terapéutico , Trastornos del Inicio y del Mantenimiento del Sueño/terapia , Nivel de Alerta/fisiología , Encéfalo/fisiopatología , Enfermedad Crónica , Comorbilidad , Quimioterapia Combinada , Humanos , Pronóstico , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/fisiopatología , Resultado del TratamientoRESUMEN
Objective: The aims of this review were to describe the relationship between obstructive sleep apnea (OSA) and psychiatric disorders and provide an overview of how to recognize/manage OSA in psychiatric practice.Data Sources: A literature search of PubMed was conducted (in adults, English language, no limitation on year). Among others, main keywords included "obstructive sleep apnea" AND "psychiatric."Study Selection: Articles relevant to the treatment of OSA in psychiatric populations were selected manually.Data Extraction: No formal data charting was conducted.Results: A total of 141 articles were included from the literature search. Comorbid OSA is common among patients with psychiatric disorders, particularly depression and posttraumatic stress disorder. Evidence suggests that OSA may be an independent risk factor for the development of psychiatric conditions, as well as for suicidal ideation and attempts in psychiatric populations. Recognizing OSA in patients with psychiatric disorders can be challenging due to the overlap of symptoms (eg, sleep issues, mood changes, and vegetative symptoms) between OSA, psychiatric disorders, and side effects of psychiatric medications. Inadequately treated OSA can affect the severity of psychiatric symptoms and impair response to psychiatric treatment.Conclusions: Clinicians should not assume that all sleep-related symptoms are consequences of psychiatric illness or medication but should instead be cognizant of the potential for coexisting OSA that requires treatment. Recognizing and managing OSA in patients with psychiatric disorders are critical to improve response to treatment, quality of life, and overall health.