An online behavioural self-help intervention rapidly improves acute insomnia severity and subjective mood during the COVID-19 pandemic: a stratified randomised controlled trial.

STUDY OBJECTIVES: Stressful life events, such as the COVID-19 pandemic, can cause acute insomnia. Cognitive behavioural therapy for acute insomnia is effective but is both time and resource-intensive. This study investigated if an online behavioural self-help intervention, which has been successfully used alongside sleep restriction for acute insomnia, reduced insomnia severity and improved mood in acute insomnia. This study also assessed good sleepers to explore if a "sleep vaccination" approach was feasible. METHODS: In this online stratified randomised controlled trial, 344 participants (103 good sleepers and 241 participants with DSM-5 acute insomnia) were randomised to receive the intervention/no intervention (good sleepers) or intervention/intervention after 28 days (poor sleepers). Insomnia severity was assessed using the ISI (primary outcome), and anxiety and depression using the GAD-7/PHQ-9 (secondary outcomes) at baseline, one week, one month and three-month follow-up. RESULTS: In people with acute insomnia, relative to baseline, there were significant reductions in ISI (dz = 1.17), GAD-7 (dz = .70) and PHQ-9 (dz = .60) scores at one week follow-up. ISI, GAD-7 and PHQ-9 scores were significantly lower at all follow-up time points, relative to baseline. Subjective diary-derived sleep continuity was unaffected. No beneficial effects upon sleep or mood were observed in good sleepers. CONCLUSIONS: An online behavioural self-help intervention rapidly reduces acute insomnia severity (within one week), and benefits mood in people with acute insomnia. These beneficial effects are maintained up to three months later. Although the use of the intervention is feasible in good sleepers, their subjective sleep was unaffected.

Nutritional interventions in treating menopause-related sleep disturbances: a systematic review.

CONTEXT: Sleep disturbances are a core symptom of menopause, which refers to the permanent cessation of menstrual periods. Nutritional interventions may alleviate menopause-related sleep disturbances, as studies have shown that certain interventions (eg, tart cherry juice, or tryptophan-rich foods) can improve relevant aspects of sleep. OBJECTIVE: The aim of this systematic review was to examine the effect of nutritional interventions for menopause-related sleep disturbances, in order to inform the subsequent development of specific interventional trials and assess their potential as a treatment for menopause-related sleep disturbances. DATA SOURCES: Published studies in English were located by searching PubMed and PsycArticles databases (until September 15, 2022). DATA EXTRACTION: Following full-text review, a final total of 59 articles were included. The search protocol was performed in accordance with PRISMA guidelines. DATA ANALYSIS: A total of 37 studies reported that a nutritional intervention improved some aspect of sleep, and 22 studies observed no benefit. Most (n = 24) studies recruited postmenopausal women, 18 recruited menopausal women, 3 recruited perimenopausal women, and 14 recruited women from multiple groups. The majority of the studies were of low methodological quality. Due to the heterogeneity of the studies, a narrative synthesis without meta-analysis is reported. CONCLUSION: Despite the large heterogeneity in the studies and choice of intervention, the majority of the identified studies reported that a nutritional intervention did benefit sleep, and that it is mainly subjective sleep that is improved. More high-quality, adequately powered, randomized controlled trials of the identified nutritional interventions are necessary. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021262367.

Stress and the hypothalamic-pituitary-adrenal axis: How can the COVID-19 pandemic inform our understanding and treatment of acute insomnia?

Stress and sleep are very closely linked, and stressful life events can trigger acute insomnia. The ongoing COVID-19 pandemic is highly likely to represent one such stressful life event. Indeed, a wide range of cross-sectional studies demonstrate that the pandemic is associated with poor sleep and sleep disturbances. Given the high economic and health burden of insomnia disorder, strategies that can prevent and treat acute insomnia, and also prevent the transition from acute insomnia to insomnia disorder, are necessary. This narrative review outlines why the COVID-19 pandemic is a stressful life event, and why activation of the hypothalamic-pituitary-adrenal axis, as a biological marker of psychological stress, is likely to result in acute insomnia. Further, this review outlines how sleep disturbances might arise as a result of the COVID-19 pandemic, and why simultaneous hypothalamic-pituitary-adrenal axis measurement can inform the pathogenesis of acute insomnia. In particular, we focus on the cortisol awakening response as a marker of hypothalamic-pituitary-adrenal axis function, as cortisol is the end-product of the hypothalamic-pituitary-adrenal axis. From a research perspective, future opportunities include identifying individuals, or particular occupational or societal groups (e.g. frontline health staff), who are at high risk of developing acute insomnia, and intervening. From an acute insomnia treatment perspective, priorities include testing large-scale online behavioural interventions; examining if reducing the impact of stress is effective and, finally, assessing whether "sleep vaccination" can maintain good sleep health by preventing the occurrence of acute insomnia, by preventing the transition from acute insomnia to insomnia disorder.

Sleep disturbances in Lewy body dementia: A systematic review.

BACKGROUND: Lewy body dementia (LBD) refers to both dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD). Sleep disturbances are common in LBD, and can include poor sleep quality, excessive daytime sleepiness (EDS), and rapid eye movement behaviour disorder (RBD). Despite the high clinical prevalence of sleep disturbances in LBD, they are under-studied relative to other dementias. The aim of the present systematic review was to examine the nature of sleep disturbances in LBD, summarise the effect of treatment studies upon sleep, and highlight specific and necessary directions for future research. METHODS: Published studies in English were located by searching PubMED and PSYCArticles databases (until 10 June 2022). The search protocol was pre-registered in PROSPERO (CRD42021293490) and performed in accordance with PRISMA guidelines. RESULTS: Following full-text review, a final total of 70 articles were included. These included 20 studies focussing on subjective sleep, 14 on RBD, 8 on EDS, 7 on objective sleep, and 1 on circadian rhythms. The majority of the 18 treatment studies used pharmacological interventions (n = 12), had an open-label design (n = 8), and were of low-to-moderate quality. Most studies (n = 55) included only patients with DLB. Due to the heterogeneity of the studies, we reported a narrative synthesis without meta-analysis. CONCLUSIONS: At least one form of sleep disturbance may be present in as many as 90% of people with LBD. Subjectively poor sleep quality, excessive daytime sleepiness, and RBD are more common and severe in LBD relative to other dementias.

Pre-Sleep Cognitive Arousal Is Unrelated to Sleep Misperception in Healthy Sleepers When Unexpected Sounds Are Played during Non-Rapid Eye Movement Sleep: A Polysomnography Study.

BACKGROUND: It is well-established that environmental noise can disrupt sleep, and cause a mismatch between subjective and objective sleep, which is known as "sleep misperception". Naturalistic studies indicate that pre-sleep cognitive arousal and sleep misperception are associated in the context of noise. However, it is not known if this is the case when ecologically valid noises are specifically played during non-rapid eye movement (NREM) sleep, which is susceptible to noise-related disruption. The present study evaluated if pre-sleep cognitive arousal was associated with sleep misperception in healthy normal sleepers, when unexpected ecologically valid common nocturnal noises were played during NREM sleep. METHODS: Eighteen healthy sleepers (Mage = 23.37 years, SDage = 3.21 years) participated. Sleep was measured objectively on three consecutive nights using polysomnography, in a sleep laboratory environment, and subjectively, through participant estimates of total sleep time (TST). Night 1 was a baseline night where no noises were played. On Night 2, noises, which were chosen to be representative of habitual nocturnal noises heard in home environments, were played to participants via in-ear headphones after 5 min of objective sleep. RESULTS: Unexpectedly, habitual pre-sleep cognitive arousal was not associated with subjective-objective TST discrepancy on Night 2. CONCLUSIONS: These results suggest that in healthy sleepers, when ecologically valid noises are played unexpectedly during NREM sleep in an unfamiliar sleep laboratory environment the subjective experience of sleep is not associated with pre-sleep cognitive arousal, or negatively impacted by noise exposure.

How can light be used to optimize sleep and health in older adults?

Globally, society is aging and changes to the timing and quality of sleep are often observed in older adults (aged ≥65years). Good sleep quality, and sufficient sleep duration, is necessary to maintain good physical and psychological health, and strategies which optimize good sleep will be important in an aging society. Light has a very powerful effect upon sleep and circadian rhythms, and has specific advantages including the relative low cost, ease of administration and lack of interaction with other medications. For this reason, bright light treatment is a promising method for optimizing sleep and circadian rhythmicity in older adults. In this chapter, we examine whether bright light treatment could be used to optimize sleep, circadian rhythms, and health in older adults. We also outline a range of methodological considerations which need to be addressed to increase the feasibility, acceptability and effectiveness of light treatment in older adults.

Transcranial Direct Current Stimulation in the Treatment of Visual Hallucinations in Charles Bonnet Syndrome: A Randomized Placebo-Controlled Crossover Trial.

OBJECTIVE: To investigate the potential therapeutic benefits and tolerability of inhibitory transcranial direct current stimulation (tDCS) on the remediation of visual hallucinations in Charles Bonnet syndrome (CBS). DESIGN: Randomized, double-masked, placebo-controlled crossover trial. PARTICIPANTS: Sixteen individuals diagnosed with CBS secondary to visual impairment caused by eye disease experiencing recurrent visual hallucinations. INTERVENTION: All participants received 4 consecutive days of active and placebo cathodal stimulation (current density: 0.29 mA/cm2) to the visual cortex (Oz) over 2 defined treatment weeks, separated by a 4-week washout period. MAIN OUTCOME MEASURES: Ratings of visual hallucination frequency and duration following active and placebo stimulation, accounting for treatment order, using a 2 × 2 repeated-measures model. Secondary outcomes included impact ratings of visual hallucinations and electrophysiological measures. RESULTS: When compared with placebo treatment, active inhibitory stimulation of visual cortex resulted in a significant reduction in the frequency of visual hallucinations measured by the North East Visual Hallucinations Interview, with a moderate-to-large effect size. Impact measures of visual hallucinations improved in both placebo and active conditions, suggesting support and education for CBS may have therapeutic benefits. Participants who demonstrated greater occipital excitability on electroencephalography assessment at the start of treatment were more likely to report a positive treatment response. Stimulation was found to be tolerable in all participants, with no significant adverse effects reported, including no deterioration in preexisting visual impairment. CONCLUSIONS: Findings indicate that inhibitory tDCS of visual cortex may reduce the frequency of visual hallucinations in people with CBS, particularly individuals who demonstrate greater occipital excitability prior to stimulation. tDCS may offer a feasible intervention option for CBS with no significant side effects, warranting larger-scale clinical trials to further characterize its efficacy.

Investigation of structural brain changes in Charles Bonnet Syndrome.

BACKGROUND AND OBJECTIVES: In Charles Bonnet Syndrome (CBS), visual hallucinations (VH) are experienced by people with sight loss due to eye disease or lesional damage to early visual pathways. The aim of this cross-sectional study was to investigate structural brain changes using magnetic resonance imaging (MRI) in CBS. METHODS: Sixteen CBS patients, 17 with eye disease but no VH, and 19 normally sighted people took part. Participants were imaged on a 3T scanner, with 1 mm resolution T1 weighted structural imaging, and diffusion tensor imaging with 64 diffusion directions. RESULTS: The three groups were well matched for age, sex and cognitive scores (MMSE). The two eye disease groups were matched on visual acuity. Compared to the sighted controls, we found reduced grey matter in the occipital cortex in both eye disease groups. We also found reductions of fractional anisotropy and increased diffusivity in widespread areas, including occipital tracts, the corpus callosum, and the anterior thalamic radiation. We did not find any significant differences between the eye disease participants with VH versus without VH, but did observe a negative association between hippocampal volume and VH severity in the CBS group. DISCUSSION: Our findings suggest that although there are cortical and subcortical effects associated with sight loss, structural changes do not explain the occurrence of VHs. CBS may relate instead to connectivity or excitability changes in brain networks linked to vision.

Recently developed drugs for the treatment of drug-resistant tuberculosis: a research and development case study.

Two drugs with novel mechanisms of action, the diarylquinoline bedaquiline and the nitroimidazole delamanid-as well as pretomanid from the same class of drugs as delamanid-have recently become available to treat drug-resistant tuberculosis (DR-TB) after many decades of little innovation in the field of DR-TB treatment. Despite evidence of improved efficacy and reduced toxicity of multidrug regimens including the two agents, access to bedaquiline and delamanid has been limited in many settings with a high burden of DR-TB and consistently poor treatment outcomes. Aside from regulatory, logistic and cost barriers at country level, uptake of the novel agents was complicated by gaps in knowledge for optimal use in clinical practice after initial market approval. The main incentives of the current pharmaceutical research and development paradigm are structured around obtaining regulatory approval, which in turn requires efficacy and safety data generated by clinical trials. Recently completed and ongoing clinical trials did not answer critical questions of how to provide shorter, less toxic treatment DR-TB treatment regimens containing bedaquiline and delamanid and improve patient outcomes. Voluntary generation of evidence that is not part of this process-yet essential from a clinical or policy perspective-has been left to non-sponsor partners and researchers, often without collaborative efforts to improve post-regulatory approval access to life-saving drugs. Additionally, these efforts are currently not recognised in the value chain of the research and development process, and there are no incentives to make this critical research happen in a coordinated way.

Pre-Sleep Cognitive Arousal Is Negatively Associated with Sleep Misperception in Healthy Sleepers during Habitual Environmental Noise Exposure: An Actigraphy Study.

Specific noises (e.g., traffic or wind turbines) can disrupt sleep and potentially cause a mismatch between subjective sleep and objective sleep (i.e., "sleep misperception"). Some individuals are likely to be more vulnerable than others to noise-related sleep disturbances, potentially as a result of increased pre-sleep cognitive arousal. The aim of the present study was to examine the relationships between pre-sleep cognitive arousal and sleep misperception. Sixteen healthy sleepers participated in this naturalistic, observational study. Three nights of sleep were measured using actigraphy, and each 15-s epoch was classified as sleep or wake. Bedside noise was recorded, and each 15-s segment was classified as containing noise or no noise and matched to actigraphy. Participants completed measures of habitual pre-sleep cognitive and somatic arousal and noise sensitivity. Pre-sleep cognitive and somatic arousal levels were negatively associated with subjective−objective total sleep time discrepancy (p < 0.01). There was an association between sleep/wake and noise presence/absence in the first and last 90 min of sleep (p < 0.001). These results indicate that higher levels of habitual pre-sleep arousal are associated with a greater degree of sleep misperception, and even in healthy sleepers, objective sleep is vulnerable to habitual bedside noise.

Quantifying test-retest reliability of repeated objective attentional measures in Lewy body dementia.

Objective cognitive impairment is a feature of Lewy body dementia (LBD), and computerised attentional tasks are commonly used as outcome measures in interventional trials. However, the reliability of these measures, in the absence of interventions, are unknown. This study examined the reliability of these attentional measures at short-term and longer-term follow-up stages. LBD patients (n = 36) completed computerised attentional tasks [simple and choice reaction time, and digit vigilance (SRT, CRT, DV)] at short-term (Day 0-Day 5) and longer-term (4 and 12 weeks) follow-up. Intra-class correlations (ICCs) were calculated to assess test-retest reliability. At short-term, the reciprocal SRT, CRT and DV mean reaction time to correct answers, the reciprocal DV coefficient of variation, and reciprocal power of attention (PoA) all showed excellent levels of reliability (all ICCs > 0.90). The reciprocal PoA showed the highest level of reliability (ICC = 0.978). At longer-term follow-up, only the reciprocal PoA had excellent levels of reliability (ICC = 0.927). Reciprocal SRT, CRT and DV reaction time to correct answers, and the CRT coefficient of variation values, showed good levels of test-retest reliability (ICCs ≥ 0.85). Contrary to expectations, most attentional measures demonstrated high levels of test-retest reliability at both short-term and longer-term follow-up time points. The reciprocal PoA composite measure demonstrated excellent levels of test-retest reliability, both in the short-term and long-term. This indicates that objective attentional tasks are suitable outcome measures in LBD studies and that the composite PoA measure may offer the highest levels of reliability.

Poor false sleep feedback does not affect pre-sleep cognitive arousal or subjective sleep continuity in healthy sleepers: a pilot study.

Modern wearable devices calculate a numerical metric of sleep quality (sleep feedback), which are intended to allow users to monitor and, potentially, improve their sleep. This feedback may have a negative impact on pre-sleep cognitive arousal, and subjective sleep, even in healthy sleepers, but it is not known if this is the case. This pilot study examined the impact of poor false sleep feedback, upon pre-sleep arousal and subjective sleep continuity in healthy sleepers. A total of 54 healthy sleepers (Mage = 30.19 years; SDage = 12.94 years) were randomly allocated to receive good, or poor, false sleep feedback, in the form of a numerical sleep score. Participants were informed that this feedback was a true reflection of their habitual sleep. Pre-sleep cognitive and somatic arousal was measured at baseline, immediately after the presentation of the feedback, and one week afterwards. Subjective sleep continuity was measured using sleep diaries for one week before, and after, the presentation of the feedback. There were no significant differences between good and poor feedback groups in terms of pre-sleep cognitive arousal, or subjective sleep continuity, before or after the presentation of the sleep feedback. The presentation of false sleep feedback, irrespective of direction (good vs. poor) does not negatively affect pre-sleep cognitive arousal or subjective sleep continuity in healthy sleepers. Whilst the one-off presentation of sleep feedback does not negatively affect subjective sleep, the impact of more frequent sleep feedback on sleep should be examined.

Testing an early online intervention for the treatment of disturbed sleep during the COVID-19 pandemic in self-reported good and poor sleepers (Sleep COVID-19): study protocol for a randomised controlled trial.

BACKGROUND: Theoretical models of insomnia suggest that stressful life events, such as the COVID-19 pandemic, can cause acute insomnia (short-term disruptions to sleep). Early interventions may prevent short-term sleep problems from progressing to insomnia disorder. Although cognitive behavioural therapy for insomnia (CBT-I) is effective in treating insomnia disorder, this can be time and resource-intensive. Further, online interventions can be used to deliver treatment to a large number of individuals. The objective of this study is to investigate if an online behavioural intervention, in the form of a leaflet, which has been successfully used alongside CBT-I for acute insomnia, can reduce symptoms of acute insomnia in poor sleepers. METHODS: A total of 124 self-reported good and poor sleepers will be enrolled in an online stratified randomised controlled trial. After baseline assessments (T1), participants will complete a 1-week pre-intervention sleep monitoring period (T2) where they will complete daily sleep-diaries. Poor sleepers (n = 62) will be randomly allocated to an invention or wait-list group, where they will receive the intervention (T3), or will do so after a 28-day delay. Good sleepers (n = 62) will be randomly assigned to an intervention or no intervention group. All participants will complete a 1-week post intervention sleep monitoring period using daily sleep diaries (T4). Participants will be followed up at 1 week (T5), 1 month (T6) and 3 months (T7) post intervention. The primary outcome measure will be insomnia severity, measured using the Insomnia Severity Index. Secondary outcome measures will include subjective mood and subjective sleep continuity, measured using sleep diaries. Data will be analysed using an intention-to-treat approach. DISCUSSION: It is expected that this online intervention will reduce symptoms of acute insomnia in self-reported short-term poor sleepers, and will also prevent the transition to poor sleep in good sleepers. We expect that this will demonstrate the feasibility of online interventions for the treatment and prevention of acute insomnia. Specific advantages of online approaches include the low cost, ease of administration and increased availability of treatment, relative to face-to-face therapy. TRIAL REGISTRATION: ISRCTN43900695 (Prospectively registered 8th of April 2020).

Sleep disturbances and physical health problems in caregivers of children with ASD.

OBJECTIVES: Caregivers of children with autism spectrum disorder self-report more physical health problems than controls. Sleep disturbances are also more prevalent in caregivers, and are positively associated with physical health problems. The negative impact of caring for a child with ASD on physical health therefore, might occur indirectly via poorer sleep. METHODS: Participants, of which n = 43 were caregivers and n = 17 were controls, completed self-report measures of physical health problems and, to capture objective measures of sleep, wore an actigraphy device. RESULTS: Physical health problems were greater in caregivers, as were subjective reports of disturbed sleep. Objectively, waking after sleep onset (WASO) and average number of awakenings were higher, as was sleep latency, and sleep efficiency was poorer, in caregivers. Total sleep time however, was greater in caregivers, as was time in bed. Physical health problems, while unrelated to actigraphy measures, were positively associated with self-reported sleep disturbances. Caregivers' increased risk for physical health problems occurred indirectly via greater self-reports of disturbed sleep. CONCLUSIONS: Interventions that help alleviate caregivers' sleep disturbances might be effective, by reducing physical health problems, for improving quality of provided care, and this might be explored in future research.

Testing an early online intervention for the treatment of disturbed sleep during the COVID-19 pandemic (Sleep COVID-19): structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The primary aim of the present study is to examine the efficacy of an online intervention for poor sleep in the context of an ongoing stressful major life event, by assessing if this intervention can reduce insomnia severity at short-term (one week post-intervention) and long-term (one and three months post-intervention) follow-up time points. It is hypothesised that the intervention will: 1) reduce insomnia severity in poor sleepers, compared to wait-list control poor sleepers, and good sleepers; 2) reduce subjective symptoms of anxiety and depression in all groups, and 3) prevent the transition to acute insomnia in good sleepers. TRIAL DESIGN: This study is a cluster randomised controlled trial. PARTICIPANTS: Both healthy good sleepers, who do not report having any current sleep problems, and individuals who report having sleep problems, will be recruited for the present study. This is a single-site study (Northumbria University). This study will be delivered using the internet and there are no geographic restrictions. Individuals who self-report as poor sleepers will meet DSM-5 criteria for acute insomnia, which is where individuals: 1) have difficulties in falling asleep, staying asleep, or awakening too early for at least three nights per week, for a time period of between two weeks and three months; and 2) report experiencing distress or impairment caused by sleep loss. Both 1) and 2) must have occurred despite the individual having had an adequate opportunity for sleep during this time period. Good sleepers will be individuals who do not have current sleep problems. All participants must have a sufficient level of English comprehension to understand and complete study measures. Individuals cannot participate if they report having chronic sleep problems (where they have existed for more than three months immediately prior to providing consent), nor will individuals who are actively seeking treatment for their sleep problems irrespective of how long they have had the sleep problem. Individuals also cannot participate if they have a self-reported history of head injuries, or if they have a self-reported diagnosis of schizophrenia, epilepsy or personality disorder, as the distraction techniques involved in the insomnia intervention may increase rumination in individuals with these conditions, and influence the effectiveness of the intervention. INTERVENTION AND COMPARATOR: Participants who receive the intervention will be provided with an online version of a self-help leaflet. A printed version of this leaflet has been successfully used in previous treatment studies, which have been conducted by our research group. Participants will be encouraged to download, save or print out this leaflet, which will be provided in PDF format. There will be no restrictions on use and participants will be encouraged to refer to this leaflet as often as they wish to. Briefly, this self-help leaflet aims to improve sleep by identifying and addressing sleep-related dysfunctional thinking by providing education about sleep, providing techniques to distract from intrusive worrisome thoughts at night, and providing guidelines for sleep-related stimulus control. The comparator is a wait-list control (i.e. where they will receive the intervention after a one month delay) group. MAIN OUTCOMES: The primary outcome measure will be insomnia severity, as measured using the Insomnia Severity Index (Bastien, Vallières, & Morin, 2001), assessed immediately prior to the intervention and at one week, one month and three months post-intervention, compared to baseline. Secondary outcome measures will include subjective mood, measured using the 7-item Generalised Anxiety Disorder Questionnaire (GAD-7; Spitzer, Kroenke, Williams, & Lowe, 2006)) and 9-item Patient Health Questionnaire (PHQ-9; Kroenke, Spitzer, & Williams, 2001), assessed immediately prior to the intervention, and one week, one month and three months post-intervention, compared to baseline. Additionally, subjective sleep continuity, derived from sleep diaries (Carney et al., 2012), will be compared pre and post-intervention. RANDOMISATION: This study will operate as a cluster randomised controlled trial. Good sleepers will be randomised into an intervention or a no-intervention group, with a 1:1 allocation. Poor sleepers will be randomised into an intervention or wait-list control group, with a 1:1 allocation. Randomisation will be conducted automatically using Qualtrics study software, where block sizes will be equal and randomisation will be computer-generated. BLINDING (MASKING): Participants will not be blinded to group assignment. The outcomes will be assessed by a blinded investigator. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The minimum sample size is 60. A total of 30 poor sleepers will be randomised to the intervention or wait-list control group. A total of 30 good sleepers will be randomised to the intervention or no intervention group. TRIAL STATUS: Recruitment for this study has yet to start. It is anticipated that recruitment will begin in August 2020 and end in April 2022. The current study protocol is version 1.0 (20 July 2020) TRIAL REGISTRATION: This study was prospectively registered in the ISRCTN registry (registration number ISRCTN43900695 , date of registration: 8 April 2020). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Experienced Demand Does Not Affect Subsequent Sleep and the Cortisol Awakening Response.

PURPOSE: Stress is associated with subjective and objective sleep disturbances; however, it is not known whether stress disrupts sleep and relevant physiological markers of stress immediately after it is experienced. The present study examined whether demand, in the form of cognitive tasks, disrupted sleep and the cortisol awakening response (CAR), depending on whether it was experienced or just anticipated. PARTICIPANTS AND METHODS: Subjective and objective sleep was measured in 22 healthy adults on three nights (Nights 0-2) in a sleep laboratory using sleep diaries and polysomnography. Saliva samples were obtained at awakening, +15, +30, +45 and +60 minutes on each subsequent day (Day 1-3) and CAR measurement indices were derived: awakening cortisol levels, the mean increase in cortisol levels (MnInc) and total cortisol secretion (AUCG). On Night 1, participants were informed that they were required to complete a series of demanding cognitive tasks within the sleep laboratory during the following day. Participants completed the tasks as expected or unexpectedly performed sedentary activities. RESULTS: Compared to the no-demand group, the demand group displayed significantly higher levels of state anxiety immediately completing the first task. There were no subsequent differences between the demand and no-demand groups in Night 2 subjective sleep continuity, objective sleep continuity or architecture, or on any Day 3 CAR measure. CONCLUSION: These results indicate that sleep and the CAR are not differentially affected depending on whether or not an anticipated stressor is then experienced. This provides further evidence to indicate that the CAR is a marker of anticipation and not recovery. In order to disrupt sleep, a stressor may need to be personally relevant or of a prolonged duration or intensity.

Consecutive sessions of transcranial direct current stimulation do not remediate visual hallucinations in Lewy body dementia: a randomised controlled trial.

BACKGROUND: Complex visual hallucinations are common in Lewy body dementia (LBD) and can cause significant patient and caregiver distress. Current treatments are primarily pharmacological in nature and have limited efficacy and associated side effects. The objective of this study was to assess the effects of consecutive sessions of transcranial direct current stimulation (tDCS) on visual hallucination frequency and severity in LBD, at short-term and long-term follow-up stages. METHODS: The study was a randomised, double-blind, placebo-controlled trial involving 40 participants with LBD (Mage = 75.52 years, SDage = 8.69 years) which was conducted at a single site between November 2013 and December 2017. Participants received two consecutive 20-min sessions of active (0.048 mA/cm2) or placebo tDCS, separated by a 30-min break, over 5 consecutive days. The anodal electrode was applied to the right parietal cortex (P4) and the cathodal electrode was applied to the occipital cortex (Oz). The primary outcome measure was the Neuropsychiatric Inventory (NPI) hallucinations subscale, as completed by a caregiver/informant at baseline and day 5 (short-term) follow-up, and month 1 and month 3 (long-term) follow-up. Secondary outcome measures included visual cortical excitability, as measured using transcranial magnetic stimulation, computerised attentional and visuoperceptual tasks, and measures of global cognition and cognitive fluctuations. RESULTS: Complete study data were obtained from 36 participants. There was an overall improvement in visual hallucinations (NPI) for both groups at day 5 relative to baseline, with a medium-to-large effect size; however, compared to placebo, active tDCS did not result in any improvements in visual hallucinations (NPI) at day 5 relative to baseline, or at month 1 or month 3 follow-up time points. Additionally, comparisons of secondary outcome measures showed that active tDCS did not result in any improvements on any measure (visual cortical excitability, attentional and visuoperceptual tasks or cognitive measures) at any time point. CONCLUSIONS: Repeated consecutive sessions of parietal anodal tDCS, and occipital cathodal tDCS, do not improve visual hallucinations or visuoperceptual function, or alter visual cortical excitability in LBD. TRIAL REGISTRATION: ISRCTN, ISRCTN40214749 . Registered on 25 October 2013.

Exploration of potential objective and subjective daily indicators of sleep health in normal sleepers.

PURPOSE: While the concept of "sleep health" has only recently been defined, how it relates to both subjective and objective sleep parameters is yet to be determined. The current study aimed to identify potential indicators of poorer sleep health, from subjective and objective daily sleep characteristics, in normal sleepers. PARTICIPANTS AND METHODS: Eighty-three individuals aged 18-65 years with no history of sleep disorders, chronic physical or psychiatric illnesses, or substance misuse were recruited from the North of England. Secondary analysis of a series of standardized studies, which included psychometrics, actigraphy, and an in-lab polysomnography (PSG) component, was undertaken. Questions from several psychometric sleep scales were combined to create an aggregate measure of sleep health status. Subjective sleep continuity was assessed by 2-week sleep diary. Objective measures comprised two continuous weeks of actigraphy and two nights of in-lab PSG. RESULTS: Significant negative correlations were evident between sleep health scores and both diary-derived subjective sleep latency (SL; diary) and actigraphy-derived SL (actigraphy). This was reflected by independent samples t-test between high and low sleep health groups. No relationships between sleep health and PSG parameters were observed. Regression analyses indicated sleep latencies from both the sleep diary and actigraphy as significant predictors, explaining 28.2% of the variance in sleep health. CONCLUSION: Perceived increases in SL appear to be a primary indicator of declining sleep health in normal sleepers. The majority of objective sleep parameters, including gross PSG sleep parameters, appear not to be sensitive to sleep health status in normal sleepers. Future research is needed to understand the physical and psychological correlates of sleep health in larger samples.