Trazodone improves sleep parameters in Alzheimer disease patients: a randomized, double-blind, and placebo-controlled study.

OBJECTIVES: There are no randomized clinical trials regarding efficacy of trazodone in the treatment of sleep disturbances (SD) in patients with Alzheimer disease (AD). We tested the efficacy and safety of trazodone to treat SD in patients with AD. DESIGN: We conducted a double-blind, randomized and controlled trial during periods of 7-9 days at baseline and 2 weeks of treatment. SETTING: Geriatric medical center of the university's general hospital. PARTICIPANTS: Individuals with probable AD and SD. The complete analysis comprised 30 patients assigned to either the active treatment group (N = 15) or the placebo group (N = 15). INTERVENTION: Patients received 50 mg of trazodone once daily at 10:00 P.M. or placebo in a 1:1 ratio for 2 weeks. MEASUREMENTS: Patients were evaluated using actigraphy and structured scales before and after intervention. RESULTS: Compared with the placebo group, trazodone users slept 42.5 more minutes per night and had their nighttime percent sleep increased 8.5 percentage points according to actigraphic data post-treatment. Neither trazodone nor placebo induced significant daytime sleepiness or naps. The treatments with trazodone or placebo did not show any effects either on cognition (Mini-Mental State Examination, forward/backward digit span task, letter-number sequencing, arithmetic, digit symbol-coding, and symbol search) or functionality (Katz index). There were no differences in frequency or severity rating of adverse events between the groups. CONCLUSIONS: This study shows significant therapeutic effects of trazodone 50 mg in community-dwelling AD patients with SD.

Late evening electric light exposure is associated with low sleep regularity in adolescents living in rural areas.

In this study, we tested the prediction that sleep regularity would be lower in adolescents exposed to late evening electric light (LEEL) than in those without exposure to it. The Sleep Regularity Index was calculated based on actigraph recordings from adolescents living in rural communities in Argentina and Brazil that were either exposed to LEEL or not. The effect of the LEEL on sleep variables was tested using linear models considering sex and age, as well as accounting for the differences between countries. Sleep onset was delayed, sleep duration shortened, and Sleep Regularity Index was 4 [1-8] points lower in the group exposed to LEEL (p = .0176, eta2 =0.13). Our results show that beyond sleep phase and duration, which are known to be affected by LEEL in this age group, sleep irregularity should also be considered as an important outcome variable when assessing the adverse effects of evening light on adolescents.

Actigraphic assessment of sleep in chronic obstructive pulmonary disease.

PURPOSE: Previously, sleep in chronic obstructive pulmonary disease (COPD) has been objectively investigated only by lab-based polysomnography. The main purpose of this study was to evaluate sleep quality in COPD patients in their home environment using actigraphy. We also investigated the factors associated with sleep impairment and the relationship between objective and subjective sleep quality and daytime somnolence in these patients. METHODS: Twenty-six patients with moderate to very severe COPD and 15 controls were studied by actigraphy for at least 5 days. Subjective sleep quality was evaluated by the Pittsburgh Sleep Quality Index and daytime sleepiness by the Epworth Sleepiness Scale (ESS). Dyspnea was quantified by the modified Medical Research Council (MMRC) scale. RESULTS: COPD patients showed increased sleep latency (p = 0.003), mean activity (p = 0.003), and wake after sleep onset (p = 0.003) and reduced total sleep time (TST; p = 0.024) and sleep efficiency (p = 0.001), as compared to controls. In patients, severity of dyspnea was correlated with sleep activity (r = 0.41; p = 0.04) and TST (r = -0.46; p = 0.02) and multiple regression analysis showed that MMRC score was the best predictor of TST (p = 0.02) and sleep efficiency (p = 0.03). Actigraphy measures during daytime were not significantly different between patients and controls. Subjective sleep quality was poorer in patients than controls (p = 0.043). ESS scores were not significantly different between the two groups. Actigraphy measures were not correlated with subjective sleep quality or daytime somnolence in both groups. CONCLUSIONS: Nocturnal sleep is markedly impaired in stable COPD patients studied by actigraphy in their home environment and this impairment is related to severity of dyspnea.

Multiple positive outcomes of a later school starting time for adolescents.

OBJECTIVE: We tested the effect of later school start time (LSST) by 1 hour during 1 week on sleep, sleepiness, and mood profile using within-subject design. DESIGN: A within-subject 3-weeks-long interventional study. A baseline week with school starting at 7:30 AM (week A), followed by an intervention week with school starting at 8:30 AM (week B), and a recovery week with school start time back to 7:30 AM (week C). Mixed model for repeated measures analysis was applied to test for the LSST effect between weeks. SETTING: A private high school with high level of socioeconomic status. PARTICIPANTS: Forty-eight adolescents from 3 different high school years. MEASUREMENTS: Participants were invited to wear actigraphs continuously during the 3 experimental weeks. Somnolence was obtained every school day twice, at arrival and before departure of school. Sleep quality and mood profile were evaluated by standard measures by the end of each school week, resulting in 3 repeated measures for each variable. RESULTS: Thirty-eight adolescents completed the study. Adolescents woke up later during week B (7:42 ± 00:30) in comparison to weeks A (6:54 ± 00:12) and C (6:46 ± 00:15) (p < .001), with no significant change on sleep onset between weeks (p = .657), resulting in a longer sleep duration in week B (p < .001). Significant improvements on sleepiness and mood profile were also reported during week B. CONCLUSIONS: Starting school later was effective in improving multiple aspects from sleep patterns, subjective sleepiness, and mood profile.

Are We Ready to Implement Circadian Hygiene Interventions and Programs?

Circadian hygiene, a concept not to be confused with the notion of public or social hygiene, should be discussed among experts and society. Light-dark cycles and other possible synchronizers of the human circadian timing system affect ways of life, including sleeping, eating, working and physical activity. Some of these behaviors have also been investigated individually as synchronizers (e.g., eating times). Therefore, the knowledge held today about circadian rhythms, and their implications for health, allows future perspectives in this field to be mapped. The present article summarizes the latest knowledge on factors influencing circadian rhythms to discuss a perspective for the future of health promotion based on circadian hygiene. However, it is important to highlight that circadian hygiene is the product of an imbrication of individual and societal involvement. First, it is important to adopt practices and devise public health policies in line with circadian hygiene. Second, individual healthy habits require internal rhythms to be examined. Last, the research agenda on circadian hygiene can be developed on a public as well as individual level, raising the question as to how much society is willing to embrace this change.

Potential link between caffeine consumption and pediatric depression: A case-control study.

BACKGROUND: Early-onset depressive disorders can have severe consequences both from developmental and functional aspects. The etiology of depressive disorders is complex and multi-factorial, with an intricate interaction among environmental factors and genetic predisposition. While data from studies on adults suggest that caffeine is fairly safe, effects of caffeine in children, who are in period of rapid brain development, are currently unknown. Furthermore, systematic research addressing the relationship between depressive symptoms in children and caffeine consumption is lacking.The present study examined the effects of caffeine consumption on depressed mood in children with depression and non-depressed participants. METHODS: Children and adolescents (n = 51) already enrolled in an ongoing longitudinal study, aged 9-12 years, were assessed for depressive symptoms with the Children Depressive Inventory (CDI). Psychopathological symptoms were assessed with the Child Behavioral Checklist (CBCL) and eating habits were assessed with the Nutrition-Behavior Inventory (NBI) 1. The children were compared to control children without psychopathology attending public schools in a Southern Brazilian city. RESULTS: Participants with CDI scores ≥ 15 (mean = 19; S.D. = 4) also had high NBI scores (mean = 52; S.D. = 19, p < 0.001) suggestive of a relationship between depressive symptoms and environmental factors, in this case nutrition/behavior. Additional linear regression adjusted statistical analysis, considering the factors of consumption of sweets and caffeine individually, showed that caffeine, but not sweets, was associated with depressive symptoms. CONCLUSIONS: These findings indicate that depressed children consume more caffeinated drinks than non-depressed children. Nonetheless while a strong association between depressive symptoms and caffeine consumption among children was found, further research should investigate whether or not this association is due to a cause and effect relationship.

Chronic sleep restriction in the rotenone Parkinson's disease model in rats reveals peripheral early-phase biomarkers.

Parkinson's disease (PD) is a chronic disorder that presents a range of premotor signs, such as sleep disturbances and cognitive decline, which are key non-motor features of the disease. Increasing evidence of a possible association between sleep disruption and the neurodegenerative process suggests that sleep impairment could produce a detectable metabolic signature on the disease. In order to integrate neurocognitive and metabolic parameters, we performed untargeted and targeted metabolic profiling of the rotenone PD model in a chronic sleep restriction (SR) (6 h/day for 21 days) condition. We found that SR combined with PD altered several behavioural (reversal of locomotor activity impairment; cognitive impairment; delay of rest-activity rhythm) and metabolic parameters (branched-chain amino acids, tryptophan pathway, phenylalanine, and lipoproteins, pointing to mitochondrial impairment). If combined, our results bring a plethora of parameters that represents reliable early-phase PD biomarkers which can easily be measured and could be translated to human studies.

State of the art on targeted memory reactivation: Sleep your way to enhanced cognition.

Targeted memory reactivation is a fairly simple technique that has the potential to influence the course of memory formation through application of cues during sleep. Studies have shown that cueing memory during sleep can lead to either an enhanced or decreased representation of the information encoded in the targeted networks, depending on experimental variations. The effects have been associated with sleep parameters and accompanied by activation of memory related brain areas. The findings suggest a causal role of neuronal replay in memory consolidation and provide evidence for the active system consolidation hypothesis. However, the observed inconsistencies across studies suggest that further research is warranted regarding the underlying neural mechanisms and optimal conditions for the application of targeted memory reactivation. The goal of the present review is to integrate the currently available experimental data and to provide an overview of this technique's limitations and pitfalls, as well as its potential applications in everyday use and clinical treatment. Exploring the open questions herein identified should lead to insight into safer and more effective ways of adjusting memory representations to better suit individual needs.

Translation and validation of the Pediatric Daytime Sleepiness Scale (PDSS) into Brazilian Portuguese.

OBJECTIVE: The aim of this study was to translate and validate the Pediatric Daytime Sleepiness Scale (PDSS) into Brazilian Portuguese. METHODS: The translation/validation process was carried out through translation, back translation, technical review, assessment of verbal comprehension/clarity of the scale by experts and a focus group, test-retest, and application of the tool. The reproducibility analysis was performed by applying the PDSS in test-retest; internal consistency was verified by applying the scale in 90 children and adolescents. RESULTS: The mean score of the sum of PDSS questions was 15.6 (SD=5.0) points. The PDSS showed appropriate indicators of content validation and clarity for the Brazilian Portuguese version. The internal consistency analysis showed a Cronbach's alpha of 0.784. The PDSS showed adequate reproducibility. The PDSS scores showed a significant and negative correlation with time spent in bed (r=-0.214; p=0.023). CONCLUSION: The Brazilian Portuguese version of the PDSS shows satisfactory indicators of validity and can be applied in clinical practice and scientific research.

Association of the length polymorphism in the human Per3 gene with the delayed sleep-phase syndrome: does latitude have an influence upon it?

STUDY OBJECTIVES: The objective of this study is to analyze the influence of a previously reported hPer3 gene-length polymorphism in the delayed sleep-phase syndrome and in morningness-eveningness tendencies at low latitudes in the southern hemisphere. DESIGN: We have genotyped a length polymorphism in the hPer3 gene characterized by a short repeat allele (4-repeat) and a long repeat allele (5-repeat). PARTICIPANTS: Seventeen patients with delayed sleep-phase syndrome; 156 volunteers chosen according to Horne-Ostberg questionnaire to have morning, intermediate, or evening preference; and 110 volunteers with no Horne-Ostberg score as a sample of the general population. RESULTS: We have found a higher frequency of 5-repeat allele in the delayed sleep-phase syndrome group and an association of this polymorphism with diurnal preference. CONCLUSION: Our results suggest that latitude has a role in the influence of hPer3 gene polymorphism on delayed sleep-phase syndrome and confirm previous data showing its association with morningness-eveningness tendencies.

Wrist actigraphy for measuring sleep in intervention studies with Alzheimer's disease patients: application, usefulness, and challenges.

Sleep disorders are common in patients with Alzheimer's disease (AD). An important aspect of intervention studies in patients with sleep disorders is the choice of assessment strategy. This paper presents a literature review concerning assessment strategies for measuring sleep in intervention studies with AD patients, with a focus on actigraphy. Thirty-seven articles were selected for this review, having analysis of sleep/nocturnal rhythm disturbances by actigraphy as the primary or secondary outcome. The advantages and limitations of actigraphy were discussed vis-à-vis polysomnography and subjective interventions. The following methodological aspects were addressed: impact of experimental design and patient setting, inclusion and exclusion criteria, placement of the actigraphy device, adherence to the regimen, duration of recordings and the choice of sleep parameters. Our analyses suggest that the methods used in intervention studies encompassing sleep disorders and dementia could be improved by increasing accuracy of diagnosis, categorization of sleep disturbances, adherence to actigraphy, and by clearly defining the variables and endpoints in each study. Also, controlling variables that could interfere with sleep and describing the data processing and analysis might improve interpretation of results.

Translation and validation of the Pediatric Daytime Sleepiness Scale (PDSS) into Brazilian Portuguese / Tradução e validação da Pediatric Daytime Sleepiness Scale (PDSS) para o português do Brasil

Abstract Objective: The aim of this study was to translate and validate the Pediatric Daytime Sleepiness Scale (PDSS) into Brazilian Portuguese. Methods: The translation/validation process was carried out through translation, back translation, technical review, assessment of verbal comprehension/clarity of the scale by experts and a focus group, test–retest, and application of the tool. The reproducibility analysis was performed by applying the PDSS in test–retest; internal consistency was verified by applying the scale in 90 children and adolescents. Results: The mean score of the sum of PDSS questions was 15.6 (SD = 5.0) points. The PDSS showed appropriate indicators of content validation and clarity for the Brazilian Portuguese version. The internal consistency analysis showed a Cronbach's alpha of 0.784. The PDSS showed adequate reproducibility. The PDSS scores showed a significant and negative correlation with time spent in bed (r = −0.214; p = 0.023). Conclusion: The Brazilian Portuguese version of the PDSS shows satisfactory indicators of validity and can be applied in clinical practice and scientific research.

Resumo Objetivo: Traduzir e validar o Pediatric Daytime Sleepiness Scale (PDSS) para o português (Brasil). Método: O processo da tradução/validação deu-se por meio da tradução, retrotradução, revisão técnica, avaliação da compreensão verbal/clareza do questionário por especialistas e por grupo focal, teste-reteste e aplicação do instrumento. A análise de reprodutibilidade fez-se por meio da aplicação da PDSS em teste-reteste e a consistência interna pela aplicação da escala em 90 crianças e adolescentes. Resultados: A pontuação média verificada no somatório das questões da PDSS foi 15,6 (5) pontos. A PDSS apresentou adequados indicadores de validade de conteúdo e clareza de linguagem em português do Brasil. A análise da consistência interna identificou alfa de Cronbach de 0,784. A PDSS apresentou adequada reprodutibilidade. Os escores da PDSS apresentaram correlação negativa e significativa com o tempo na cama (r = -0,214; p = 0,023). Conclusões: A versão em português da PDSS apresenta satisfatórios indicadores de validade e pode ser aplicada na prática clínica e em pesquisas científicas.

Neonatal exposure to constant light prevents anhedonia-like behavior induced by constant light exposure in adulthood.

Depressive episodes are associated with disturbances in circadian rhythms, and constant illumination has been reported to induce depressive-like behavior in rodents. Rats kept in constant darkness express the endogenous circadian rhythm, and most animals under constant light conditions lose circadian locomotor rhythmicity. Exposure to constant light in rats during lactation was reported to prevent this loss of circadian rhythm in adulthood. Thus, the aim of the present study was to verify whether exposure to constant light during lactation prevents anhedonia-like behavior induced by constant light in adult rats. In experiment 1, we replicated the anhedonia-like effects of constant light in adult male rats. We showed that this effect is reversed by imipramine treatment in the drinking water. In experiment 2, we subjected rats to constant darkness (neonatal-DD), constant light (neonatal-LL) or to normal light/dark cycle (neonatal-LD) during the neonatal phase and evaluated them after constant light exposure in adulthood. The group exposed to constant light during the neonatal phase did not reduce their sucrose preference and exhibited greater locomotor activity than the other groups. The neonatal-DD group exhibited decreased sucrose preference earlier than controls and had higher serum corticosterone concentrations. Prevention of arrhythymicity might protect neonatal-LL rats from anhedonia-like behavior induced by constant light, whereas constant darkness during the neonatal phase rendered the neonatal-DD group more susceptible to depressive-like behavior. These results corroborate with the literature data indicating that circadian disruption may contribute in mood disorders and that early life stress can influence stress responsivity in adulthood.