Sleep-wake Cycle Disturbances Research Articles

Familial risk for depression is associated with reduced physical activity in young adults: evidence from a wrist-worn actigraphy study

Depression is characterized by reduced physical activity and sleep-wake cycle disturbances, often considered important features of the disease. While a few studies have suggested that self-reported reduced physical activity and sleep-wake cycle disturbances might both be linked to depression vulnerability, actigraphy-based measures in vulnerable samples remain largely unexplored. This study relied on actigraphy-based parameters to test whether these disturbances characterize depression vulnerability. Seven-day actigraphy data were collected from 20 (13 female) university students with a high vulnerability to depression, which was determined by the presence of a family history of the condition but no current symptoms, and 32 (21 female) controls with neither a family history of depression nor current depressive symptoms. Daily physical activity, namely gross motor activity, was quantified as average daily acceleration and time spent engaging in moderate-vigorous physical activity (MVPA). The sleep-wake cycle and circadian rhythms were assessed as total sleep duration per night (in hours), sleep within sleep period time (in hours), sleep efficiency (%), and relative amplitude (i.e., the difference between the activity during the day and the night, which reflects circadian rhythms amplitude). Results showed that individuals with a familial risk for depression exhibited reduced daily acceleration and time spent in MVPA relative to the control group, particularly on the weekend during their free time away from scheduled activities. On the other hand, the two groups were comparable in terms of sleep estimates. Taken together, reduced physical activity, but not sleep-wake disturbances, seem to be associated with vulnerability to depression and might be a viable target for identification and prevention efforts.

Imputing missing sleep data from wearables with neural networks in real-world settings.

Sleep is a critical component of health and well-being but collecting and analyzing accurate longitudinal sleep data can be challenging, especially outside of laboratory settings. We propose a simple neural network model titled SOMNI (Sleep data restOration using Machine learning and Non-negative matrix factorIzation [NMF]) for imputing missing rest-activity data from actigraphy, which can enable clinicians to better handle missing data and monitor sleep-wake cycles of individuals with highly irregular sleep-wake patterns. The model consists of two hidden layers and uses NMF to capture hidden longitudinal sleep-wake patterns of individuals with disturbed sleep-wake cycles. Based on this, we develop two approaches: the individual approach imputes missing data based on the data from only one participant, while the global approach imputes missing data based on the data across multiple participants. Our models are tested with shift and non-shift workers' data from three independent hospitals. Both approaches can accurately impute missing data up to 24 hours of long dataset (>50 days) even for shift workers with extremely irregular sleep-wake patterns (AUC > 0.86). On the other hand, for short dataset (~15 days), only the global model is accurate (AUC > 0.77). Our approach can be used to help clinicians monitor sleep-wake cycles of patients with sleep disorders outside of laboratory settings without relying on sleep diaries, ultimately improving sleep health outcomes.

Data-driven categorization of postoperative delirium symptoms using unsupervised machine learning.

Phenotyping analysis that includes time course is useful for understanding the mechanisms and clinical management of postoperative delirium. However, postoperative delirium has not been fully phenotyped. Hypothesis-free categorization of heterogeneous symptoms may be useful for understanding the mechanisms underlying delirium, although evidence is currently lacking. Therefore, we aimed to explore the phenotypes of postoperative delirium following invasive cancer surgery using a data-driven approach with minimal prior knowledge. We recruited patients who underwent elective invasive cancer resection. After surgery, participants completed 5 consecutive days of delirium assessments using the Delirium Rating Scale-Revised-98 (DRS-R-98) severity scale. We categorized 65 (13 questionnaire items/day × 5 days) dimensional DRS-R-98 scores using unsupervised machine learning (K-means clustering) to derive a small set of grouped features representing distinct symptoms across all participants. We then reapplied K-means clustering to this set of grouped features to delineate multiple clusters of delirium symptoms. Participants were 286 patients, of whom 91 developed delirium defined according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria. Following the first K-means clustering, we derived four grouped symptom features: (1) mixed motor, (2) cognitive and higher-order thinking domain with perceptual disturbance and thought content abnormalities, (3) acute and temporal response, and (4) sleep-wake cycle disturbance. Subsequent K-means clustering permitted classification of participants into seven subgroups: (i) cognitive and higher-order thinking domain dominant delirium, (ii) prolonged delirium, (iii) acute and brief delirium, (iv) subsyndromal delirium-enriched, (v) subsyndromal delirium-enriched with insomnia, (vi) insomnia, and (vii) fit. We found that patients who have undergone invasive cancer resection can be delineated using unsupervised machine learning into three delirium clusters, two subsyndromal delirium clusters, and an insomnia cluster. Validation of clusters and research into the pathophysiology underlying each cluster will help to elucidate the mechanisms of postoperative delirium after invasive cancer surgery.

Effects of adjunctive brexpiprazole on sleep-wake and circadian parameters in youth with depressive disorders: study protocol for a clinical trial

IntroductionSleep-wake and circadian disturbance is a key feature of mood disorders with a potential causal role and particular relevance to young people. Brexpiprazole is a second-generation antipsychotic medication with demonstrated...

Endocrine biomarkers related to sleep-wake cycle and sleep disturbances in patients with bipolar disorder: A systematic review

IntroductionSleep and circadian disturbances have been widely studied in patients with bipolar disorder (BD) (Duarte Faria et al., 2015; Gonzalez, 2014). However, there is no clear evidence about the role of peripheral biomarkers of circadian cycle in this population.ObjectivesThis systematic review aims to identify potential endocrine biomarkers of circadian rhythm in blood and study their relationship with sleep problems in BD.MethodsAn electronic search of Pubmed and PsycoInfo databases were performed. It includes articles about the topic from 1991 to 2021. The search strategy was: (“Peripheral biomarkers” OR “biological markers” OR biomarker OR cortisol OR melatonin OR orexin OR hypocretin) AND (blood OR serum OR plasma) AND (“sleep-wake” OR “circadian rhythm” OR sleep OR insomnia) AND “bipolar”.Results92 records were obtained after excluding duplicates. Only five studies met the inclusion criteria (n = 499; BD = 125; unipolar depression = 148; schizophrenia = 80; controls = 146). The endocrine parameters analyzed were: cortisol (3 studies), melatonin (1 study) and orexin-A (1 study). Overall, no significant associations between these biomarkers and sleep disturbances, assessed with subjective (psychometric evaluation) and/or objective (polysomnography) measures, were detected.ConclusionsThis systematic review highlights the lack of studies that explores the role of endocrine biomarkers related to circadian function in the pathophysiology of sleep disturbances in BD.DisclosureNo significant relationships.

Safety and Effectiveness of Perospirone in Comparison to Risperidone for Treatment of Delirium in Patients with Advanced Cancer: A Multicenter Prospective Observational Study in Real-World Psycho-Oncology Settings.

The clinical benefit of perospirone for treatment of delirium in patients with advanced cancer is not sufficiently clear. The objective of this study was to compare the safety and effectiveness of perospirone to those of risperidone for the treatment of delirium in patients with advanced cancer. This is a secondary analysis of a multicenter prospective observational study in nine psycho-oncology consultation services in Japan. The study used the Delirium Rating Scale (DRS) Revised-98 to measure effectiveness and the CTCAE (Common Terminology Criteria for Adverse Events) version 4 to assess safety. Data from 16 patients who received perospirone and 53 patients who received risperidone were analyzed. The mean age was 70 years in the perospirone group and 73 years in the risperidone group. Both groups showed a significant decrease in the total score of DRS-R-98 after three days of treatment (perospirone: 11.7 (7.9-15.4) to 7.0 (3.3-10.7), difference -4.7, effect size=0.72, p=0.003; risperidone: 15.5 (13.6-17.4) to 12.2 (10.1-14.2), difference -3.3, effect size=0.55, p=0.00). The risperidone group showed significant improvements in sleep-wake cycle disturbance, orientation, attention, and visuospatial ability. In the perospirone group, there was a significant improvement of sleep-wake cycle disturbance. The median daily dose of perospirone was 4 mg/day. There were fewer episodes of somnolence as an adverse event in the perospirone group. Low-dose perospirone was thus found to be effective for the treatment of delirium in patients with advanced cancer and may be associated with fewer episodes of over-sedation as an adverse event.

A network analysis of rest-activity rhythms in young people with emerging bipolar disorders

AimsActigraphy studies of individuals with bipolar disorders (BD) suggest that illness progression may be associated with a range of progressive disruptions in 24-hour rest-activity rhythms (RAR). However, those longitudinal studies were undertaken in older adults with extended histories or illness and treatment rather than young people with emerging BD. To our knowledge, this is the first study to use network modelling to examine the statistical associations between clinical phenotypes of BD and different subsets of RAR markers. MethodsThis study of adolescents and young adults (mean age 22 years; 69% female) uses network modelling to examine which self-rated or actigraphic markers of RAR are more strongly associated with full threshold BD (referred to as Stage 2; N = 15) compared with BD-at risk syndromes (subthreshold presentations referred to as Stage 1; N = 25). ResultsNetwork analysis demonstrated that some RAR are associated with both stage of BD and a family history of BD (such as longer sleep duration and higher levels of daytime impairment). Markers of circadian rhythmicity indicated that regulation of this system is weaker in Stage 2 compared with Stage 1 of BD. LimitationsThe small subgroup samples may have undermined the ability to detect some associations between phenotypes and RAR. ConclusionsNetwork modelling may offer a useful strategy for visualizing and analysing patterns of association between RAR and clinical phenotypes defined by stage of illness, familial loading or symptom profile. This could prove useful in understanding the underlying pathophysiology of sleep-wake cycle and circadian rhythm disturbances in BD.

In utero Exposure to Valproic-Acid Alters Circadian Organisation and Clock-Gene Expression: Implications for Autism Spectrum Disorders.

Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder characterised by restrictive patterns of behaviour and alterations in social interaction and communication. Up to 80% of children with ASD exhibit sleep-wake cycle disturbances, emphasising the pressing need for novel approaches in the treatment of ASD-associated comorbidities. While sleep disturbances have been identified in ASD individuals, little has been done to assess the contribution of the circadian system to these findings. The objective of this study is to characterise circadian behaviour and clock-gene expression in a valproic acid (VPA)-induced animal model of autism to highlight perturbations potentially contributing to these disturbances. Male and female VPA-exposed offspring underwent circadian challenges, including baseline light-dark cycles, constant dark/light and light pulse protocols. Baseline analysis showed that VPA-exposed males, but not females, had a greater distribution of wheel-running behaviour across light-dark phases and a later activity offset (p < 0.0001), while controls showed greater activity confinement to the dark phase (p = 0.0256). Constant light analysis indicated an attenuated masking response and an increase in the number of days to reach arrhythmicity (p < 0.0001). A 1-h light pulse (150 lux) at CT 15 after 6 days of constant dark showed that both sexes exposed to VPA exhibited a lesser phase-shift when compared to controls (p = 0.0043). Immunohistochemical and western-blot assays reveal no alterations in retinal organisation or function. However, immunohistochemical assay of the SCN revealed altered expression of BMAL1 expression in VPA-exposed males (p = 0.0016), and in females (p = 0.0053). These findings suggest alterations within the core clockwork of the SCN and reduced photic-entrainment capacity, independent of retinal dysfunction. The results of this study shed light on the nature of circadian dysregulation in VPA-exposed animals and highlights the urgent need for novel perspectives in the treatment of ASD-associated comorbidities.

Impact of Therapeutic Ultrasound and Myofascial Release Technique on Quality of Life of Students Having Neck Pain Following Virtual Learning

Background: Neck pain is a ubiquitous complaint leading to work place absenteeism, disabilities and disturbed sleep wake cycle in many young working and studying people. In ongoing covid scenario, since there is increased use of laptops and mobile phones facilitating work from home for employee and virtual learning for students, there has been increased prevalence of non-specific neck pain among the people due to prolonged fixed flexion posture. Neck pain has become the condition of major consideration since 45% of UG students had experienced neck pain in last 12 months.&#x0D; Aims and Objectives: to evaluate combined and individual effects of Therapeutic Ultrasound and Myofascial Release Technique on Quality of Life of students suffering from neck pain owing to virtual learning.&#x0D; Methods: The participant (n=33) will be recruited in study experiencing non-specific neck pain and meeting the inclusion criteria. Three groups will be formed such that the patient in Group A will receive treated with therapeutic ultrasound. Group B will be receiving treatment using Myofascial Release Technique and Group C will be treated using combined use of both Therapeutic Ultrasound and Myofascial release Technique. The protocol will cover 1 week of treatment. Regular assessment at 0,3rd and 7th day of week will be carried out. We will evaluate using Numerical Pain Rating Scale (NPRS), Neck Disability Index (NDI), and Range of motion of neck and Manual Muscle testing of cervical musculature.&#x0D; Results: The result of the study will provide affirmation on using combination therapy of Therapeutic Ultrasound and Myofascial Release Technique in people having nonspecific neck pain.

Evaluation of the Impact of Prior-to-Admission Sleep Aid Prescribing Practices on Sleep and Delirium in the Intensive Care Unit.

Sleep disruptions in the intensive care unit (ICU) may lead to complications such as delirium. There is limited evidence addressing how sleep aid use before and during ICU admission affects outcomes. The purpose of this study is to evaluate the impact of prior-to-admission sleep aid prescribing practices in the ICU on delirium and sleep outcomes. A retrospective review was conducted of adult patients admitted to any ICU from January to June 2018 receiving a sleep aid prior to admission. Patients were categorized based on sleep aid continuation, discontinuation, or alteration during the ICU admission. The primary end point was the incidence of delirium. Secondary end points included the incidence of sleep-wake cycle disturbances, delirium scores, and ICU length of stay. A total of 291 patients were included with 109 in the continued group, 121 in the discontinued group, and 61 in the altered group. There was a similar incidence of delirium at 24 hours (P = 0.71), 48 hours (P = 0.60), 72 hours (P = 0.25), and 5 days (P = 0.48) after ICU admission. There was also no statistical difference in sleep-wake cycle disturbances or delirium scores at any time point. ICU length of stay was similar between the groups. The incidence of delirium and sleep-wake cycle disturbances was not affected by differences in prior-to-admission sleep aid prescribing patterns during ICU admission.

Cognitive dysfunction severity evaluation in dogs with naturally-occurring Cushing´s syndrome: A matched case-control study

Hypercortisolism has been associated with impairment of cognitive function in humans with Cushing's syndrome (CS), but there are currently no studies looking into this effect in dogs with CS. The present study evaluated the pattern of cognitive deficits and behavioral changes in dogs with naturally-occurring CS (NOCS). A previously published questionnaire (DISHA - disorientation, changes in interactive behavior, sleep-wake cycle disturbances, house-soiling, and changes in activity) was used to assess cognitive dysfunction (CD) in dogs with recently diagnosed CS, and in age-, sex-, and gonadal status-matched dogs (1:2), according to their owners’ perception. The questionnaire consisted of 32 multiple-choice questions, scored 0 to 96. The higher the score, the higher the severity of CD. The questionnaire included eight categories of behavioral signs, namely: disorientation, social interactions, sleep-wake cycles, house-soiling, compulsive behaviors, depressive behaviors, anxiety, and memory and learning. Of the 57 dogs assessed in the study, 19 were included in the CS group and 38 in the control group. Exclusion criteria for the control group were animals suspected of having CS, chronic glucocorticoid therapy, or glucocorticoid exposure in the past month. Dogs with CS exhibited a higher final score (Wilcoxon test) of cognitive dysfunction (W = 149, P = 0.001), especially, higher memory dysfunction (W = 96, P = 0.01), compulsive behaviors (W = 93, P = 0.04), depressive behaviors (W = 86, P = 0.03), and anxiety (W = 117, P = 0.001). There was no correlation between age and CD score in dogs with NOCS (r = 0.32, P = 0.465) and neither control dogs (r = 0.18, P = 0.051). Results suggest hypercortisolism may accelerate neurodegenerative process, thus resulting in more intense behavioral and cognitive changes than those observed in age-matched dogs without CS.

Impact of 6 Weeks Pilates Training on Menopause Specific Symptoms and Quality of Life in Menopausal Women: A Case Report

Introduction: The concept of menopause is a complete cessation of ovarian function. Most common symptom of menopause include muscle and joint ache, poor memory, lower back pain and trouble sleeping. The vasomotor and emotional domains reported less often compared with the physical and psychological domains. Such adverse changes in physical and mental health may have a negative impact on Quality of Life (QOL). Pilates is a mind body exercise focusing on muscle strength, core stability, endurance, muscle control, posture, and respiration which seems to improve both the physical and psychological components in women during menopause. The given study helps to provide the effect of 6 weeks Pilates training protocol on menopausal women’s presenting complaints as well as on her QOL.&#x0D; Complaints and clinical finding: Patient’s main concern were low back ache without any cause night sweats, fatigue, disturbed sleep wake cycle which lead to difficulties in performing activities of daily living which hampered the QOL of the patient. Physical findings revealed decrement in lower back and lower limb muscle strength along with some tightness. Scales helped to reveal that patient is having fatigue and tiredness and mat-exercise treatment protocol were formed.&#x0D; Therapeutic Intervention: 6 weeks Pilates training.&#x0D; Conclusion: As there are minimal to no evidence present in reference to this study, it helps us to provide new and proper treatment protocol and it is helpful to know the effect of the same. It showed significant improvement in the muscular strength as well as reduction in stress level and helped in enhancing the QOL of the patient.

Management of behavioral and psychological symptoms of dementia

IntroductionBehavioral and psychological symptoms of dementia (BPSD) are a heterogeneous group of clinical manifestations related to dementia, including apathy, depression, anxiety, delusions, hallucinations, disinhibition, sleep-wake cycle disturbances, aggression and agitation. BPSD have a negative impact on cognitive decline and increase complications.ObjectivesReview treatment management of BPSD including non-pharmacological and pharmacological options, but mainly interventional approaches, such as electroconvulsive therapy (ECT).MethodsWe conducted a search in PubMed and ClinicalKey with the terms: “Behavioral and psychological symptoms of dementia”; “Electroconvulsive therapy”.ResultsThe vast majority of patients with dementia will develop one or more BPSD. The etiopathogenesis of BPSD is complex and multifactorial, with multiple direct and indirect factors, namely biological, psychological and social aspects and related to changes in cholinergic, dopaminergic, noradrenergic and serotoninergic circuits. Current guidelines recommend non-pharmacological interventions as the first-line approach for BPSD. Pharmacotherapy is often applied, but it carries out the risk of serious side-effects and pharmacologic interactions. There is now growing evidence that interventional approaches, such as ECT, could be safe and efficient when previous treatment options have been exhausted or ineffective, with few contraindications and transient/limited adverse effects.ConclusionsBPSD represent a heterogeneous group of non-cognitive symptoms and behavior that affects most of dementia patients. Combination of non-pharmacological and pharmacological interventions is the recommended therapeutic for BPSD. However, there is usually limited clinical improvement and issues related to tolerability and effectiveness. Currently, ECT is considered a safe and effective option.

Sleep-wake cycle disturbances and NeuN-altered expression in adult rats after cannabidiol treatments during adolescence.

The medical uses of cannabidiol (CBD), a constituent of the Cannabis sativa, have accelerated the legal and social acceptance for CBD-based medications but has also given the momentum for questioning whether the long-term use of CBD during the early years of life may induce adverse neurobiological effects in adulthood, including sleep disturbances. Given the critical window for neuroplasticity and neuro-functional changes that occur during stages of adolescence, we hypothesized that CBD might influence the sleep-wake cycle in adult rats after their exposure to CBD during the adolescence. Here, we investigated the effects upon behavior and neural activity in adulthood after long-term administrations of CBD in juvenile rats. We pre-treated juvenile rats with CBD (5 or 30 mg/Kg, daily) from post-natal day (PND) 30 and during 2 weeks. Following the treatments, the sleep-wake cycle and NeuN expression was analyzed at PND 80. We found that systemic injections of CBD (5 or 30 mg/Kg, i.p.) given to adolescent rats (post-natal day 30) for 14 days increased in adulthood the wakefulness and decreased rapid eye movement sleep during the lights-on period whereas across the lights-off period, wakefulness was diminished and slow wave sleep was enhanced. In addition, we found that adult animals that received CBD during the adolescence displayed disruptions in sleep rebound period after total sleep deprivation. Finally, we determined how the chronic administrations of CBD during the adolescence affected in the adulthood the NeuN expression in the suprachiasmatic nucleus, a sleep-related brain region. Our findings are relevant for interpreting results of adult rats that were chronically exposed to CBD during the adolescence and provide new insights into how CBD may impact the sleep-wake cycle and neuronal activity during developmental stages.

Brief Research Report: A Pilot Study of Cognitive Behavioral Regulation Therapy (CBT-REG) for Young People at High Risk of Early Transition to Bipolar Disorders.

Attempts to increase early identification of individuals in the early stages of bipolar disorders (i.e., individuals at high risk of bipolar disorders and/or experiencing a subthreshold syndrome with bipolar symptoms) have highlighted the need to develop high benefit-low risk interventions. We suggest that any new psychological therapy should (i) be acceptable to young people seeking help for the first time, (ii) be applicable to “at risk” conditions and sub-syndromal states and (iii) consider pluripotent factors that may be linked to illness progression not only for bipolar disorders specifically but also for other potential disease trajectories. However, evidence indicates that current interventions for youth with emerging mood disorders mainly represent approaches abbreviated from “disorder-specific” therapies used with older adults and are primarily offered to first episode cases of bipolar disorders who are also receiving psychotropic medication. This brief report discusses empirical findings used to construct core targets for therapeutic interventions that might reduce or delay transition to full-threshold bipolar disorders. We describe an intervention that includes strategies for problem-solving, reducing sleep-wake cycle disturbances, self-management of rumination and that addresses the needs of individuals with “sub-threshold” presentations who are probably at risk of developing a bipolar or other major mental disorders. Outcome data from a case series of 14 youth indicates that the intervention appears to demonstrate a relatively high benefit-to-risk ratio, promising levels of engagement with the therapy modules, and the therapy appears to be acceptable to a wide range of help-seeking youth with early expressions of bipolar psychopathology.

Evaluation of association of impairment of attention with other symptoms of delirium

Aim: To evaluate the association of impairment of attention with other symptoms of delirium. Methodology: Eighty-six patients with delirium as per the Diagnostic and Statistical Manual, 5th Revision seen in the consultation-liaison psychiatry setup of a tertiary care hospital were cross-sectionally assessed on the short informant questionnaire on cognitive decline in the elderly (Retrospective), montreal cognitive assessment (MoCA), and delirium rating scale revised-98 (DRS-R98) version. Results: The mean age of the study participants was 46.6 (standard deviation [SD] – 16.4) years. All the patients had impairment in attention with the altered sleepwake cycle, acute onset of illness, with the fluctuating course and underlying physical disease. In terms of severity, the severity score was the highest for the item of sleep-wake cycle disturbances, followed by motor agitation. The mean noncognitive symptoms domain of the DRS-R98 domain were more than the mean score of the cognitive symptom domain of DRS-R98. The mean total score on MoCA was 11.9 (SD: 7.5). Higher attention impairment was associated with more severe noncognitive and cognitive symptoms and higher delirium severity as assessed by DRS-R98. Higher severity of attention deficit was also associated with higher impairment in other domains of cognition of MoCA. Cognitive symptoms, as evaluated by DRS-R98, had more significant correlations with various domains of MoCA except for language and abstraction. Conclusion: Attention deficits are the core symptom of delirium and have a significant impact on other cognitive and noncognitive symptoms of delirium.

Abnormal Sleep, Circadian Rhythm Disruption, and Delirium in the ICU: Are They Related?

Delirium is a syndrome characterized by acute brain failure resulting in neurocognitive disturbances affecting attention, awareness, and cognition. It is highly prevalent among critically ill patients and is associated with increased morbidity and mortality. A core domain of delirium is represented by behavioral disturbances in sleep-wake cycle probably related to circadian rhythm disruption. The relationship between sleep, circadian rhythm and intensive care unit (ICU)-acquired delirium is complex and likely bidirectional. In this review, we explore the proposed pathophysiological mechanisms of sleep disruption and circadian dysrhythmia as possible contributing factors in transitioning to delirium in the ICU and highlight some of the most relevant caveats for understanding the relationship between these complex phenomena. Specifically, we will (1) review the physiological consequences of poor sleep quality and efficiency; (2) explore how the neural substrate underlying the circadian clock functions may be disrupted in delirium; (3) discuss the role of sedative drugs as contributors to delirium and chrono-disruption; and, (4) describe the association between abnormal sleep-pathological wakefulness, circadian dysrhythmia, delirium and critical illness. Opportunities to improve sleep and readjust circadian rhythmicity to realign the circadian clock may exist as therapeutic targets in both the prevention and treatment of delirium in the ICU. Further research is required to better define these conditions and understand the underlying physiologic relationship to develop effective prevention and therapeutic strategies.

Long-Term, All-Day Exposure to Circadian-Effective Light Improves Sleep, Mood, and Behavior in Persons with Dementia.

Background:Persons with Alzheimer’s disease and related dementias (ADRD) frequently experience sleep–wake (circadian) cycle disturbances that lead them to remain awake at night, causing stress and fatigue for families and caregivers. Light therapy shows promise as a nonpharmacological treatment for regulating sleep in this population.Objective:We investigated the long-term impact of a circadian-effective lighting intervention on sleep, mood, and behavior problems in persons with ADRD.Methods:This 25-week clinical trial administered an all-day lighting intervention to 47 patients with ADRD in 9 senior-care facilities, employing wrist-worn actigraphy measures and standardized measures of sleep quality, mood, and behavior.Results:The intervention significantly improved Pittsburgh Sleep Quality Index scores, from an estimated mean±SEM of 11.89±0.53 at baseline to 5.36±0.63 at the end of the intervention. Additional improvements were noted for sleep efficiency data from actigraph measurements. The intervention significantly reduced Cornell Scale for Depression in Dementia scores (mean±SEM of 11.36±0.74 at baseline and 4.18±0.88 at the end of the intervention) and Cohen-Mansfield Agitation Inventory scores (mean±SEM of 47.10±1.98 at baseline and 35.33±2.23 at the end of the intervention).Conclusion:A regular circadian-effective daytime lighting intervention can improve sleep at night and reduce depression and agitation in patients with dementia living in controlled environments. More importantly, the positive effects of the tailored lighting intervention on these outcomes appear to be cumulative over time.

Post-traumatic Confusional State: A Case Definition and Diagnostic Criteria

In response to the need to better define the natural history of emerging consciousness after traumatic brain injury and to better describe the characteristics of the condition commonly labeled posttraumatic amnesia, a case definition and diagnostic criteria for the posttraumatic confusional state (PTCS) were developed. This project was completed by the Confusion Workgroup of the American Congress of Rehabilitation Medicine Brain Injury Interdisciplinary Special Interest group. The case definition was informed by an exhaustive literature review and expert opinion of workgroup members from multiple disciplines. The workgroup reviewed 2466 abstracts and extracted evidence from 44 articles. Consensus was reached through teleconferences, face-to-face meetings, and 3 rounds of modified Delphi voting. The case definition provides detailed description of PTCS (1) core neurobehavioral features, (2) associated neurobehavioral features, (3) functional implications, (4) exclusion criteria, (5) lower boundary, and (6) criteria for emergence. Core neurobehavioral features include disturbances of attention, orientation, and memory as well as excessive fluctuation. Associated neurobehavioral features include emotional and behavioral disturbances, sleep-wake cycle disturbance, delusions, perceptual disturbances, and confabulation. The lower boundary distinguishes PTCS from the minimally conscious state, while upper boundary is marked by significant improvement in the 4 core and 5 associated features. Key research goals are establishment of cutoffs on assessment instruments and determination of levels of behavioral function that distinguish persons in PTCS from those who have emerged to the period of continued recovery.

Sleep-Wake Cycle in Alzheimer's Disease Is Associated with Tau Pathology and Orexin Dysregulation.

Alzheimer's disease (AD) is the most common form of dementia. It is mainly characterized by a progressive deterioration of cognition, but sleep-wake cycle disturbances frequently occur. Irregular sleep-wake cycle, insomnia, and daytime napping usually occur in patients with AD in the course of the disease. The aim of the present study was to verify the sleep-wake cycle in mild to moderate AD patients compared to controls, and to evaluate the relationship between the sleep-wake cycle impairment and the neuropsychological testing, CSF AD biomarkers, and CSF orexin concentrations. Mild to moderate AD patients were enrolled and underwent 14-day actigraphic recording, sleep diary, neuropsychological testing, and CSF biomarkers analysis. All patients were compared to controls. Eighteen AD patients were compared to ten controls. AD patients showed the alteration of the sleep-wake cycle, featured by sleep dysregulation and daytime wake fragmentation, with respect to controls. Considering the correlation analysis, we documented the correlation between tau proteins and orexin CSF levels and sleep-wake cycle dysregulation. This study confirmed the dysregulation of sleep-wake cycle in AD patients, as reflected by the daytime wake fragmentation, irregular sleep-wake rhythm, and nocturnal sleep impairment. This sleep-wake cycle disorder correlates with AD neuropathological in vivo features and brain orexin activity. Hence, we suppose that a more marked AD pathology coupled with orexinergic system dysregulation may promote sleep-wake cycle impairment in AD patients.