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Insomnia or poor sleep quality with objective short sleep duration (hereafter referred to as ISSD) has been identified as a high-risk phenotype among middle-aged persons. We evaluated the prevalence and clinical correlates of ISSD among community-living older persons.In 3053 men from the Osteoporotic Fractures in Men Sleep Study (MrOS; average age 76.4 ± 5.5 years) and 3044 women from the Study of Osteoporotic Fractures (SOF; average age 83.6 ± 3.8 years), we evaluated the prevalence of ISSD (trouble getting to sleep within 30 minutes, waking up in the middle of the night or early morning, and/or taking a medication to help with sleep ≥3 times per week and actigraphy-estimated sleep duration6 h). Using separate logistic regression models in men and women, we evaluated the cross-sectional associations between predisposing, precipitating, and perpetuating factors for ISSD, as compared with normal sleep (no insomnia and actigraphy-estimated sleep duration of 6-9 h).Overall, 20.6% of older men and 12.8% of older women had insomnia with short sleep duration. Multiple predisposing, precipitating, and perpetuating factors were cross-sectionally associated with ISSD in both men and women. In multivariable models that adjusted for predisposing factors (demographics, multimorbidity, obesity), precipitating (depression, anxiety, central nervous system-active medication use, restless legs syndrome) and perpetuating (napping, falls) factors were significantly associated with ISSD in men and women (adjusted odds ratios ranging 1.63-4.57).In this cross-sectional study of community-living older men and women, ISSD was common and associated with multiple predisposing, precipitating, and perpetuating factors, akin to a multifactorial geriatric health condition. Future work should examine causal pathways and determine whether the identified correlates represent modifiable risk factors.

Recent initiatives to discourage overprescription of sleep medications have increased awareness of their potential adverse effects; however, it is unknown whether these efforts translated into a decline in use of these medications in the United States. We assessed recent national trends in the use of medications used for sleep disturbance.We used data from n = 29,400 participants in the 2013-2018 National Health and Nutrition Examination Survey. At each of three waves of in-person assessments, participants presented prescription bottles for all medications used in the prior month. Interviewers recorded each medication and participants self-reported duration and reasons for use. We identified all medications used for sleep disturbance and categorized medications into two categories: Food and Drug Administration-approved sleep medications and those used off-label for sleep disturbance. We examined changes in the prevalence in use of these medications across the study period.The odds of using medications for sleep disturbance decreased 31% between 2013 and 2018 (odds ratio = 0.69, 95% confidence interval = 0.51-0.93,Use of prescription medications for sleep disturbance declined nationally, suggesting a possible effect of efforts to curb overprescription and encourage judicious use of these agents. Future research needs to examine whether these changes have coincided with improved population sleep health.Kaufmann CN, Spira AP, Wickwire EM, et al. Declining trend in use of medications for sleep disturbance in the United States from 2013 to 2018.

Poor sleep, including short sleep duration, is common among caregivers of persons with dementia. However, it is unclear whether poor sleep is consistent across both self-reported and objective measures of sleep in caregivers. This study aimed to test the role of caregiving status (caregivers vs noncaregivers) on the discrepancy between self-reported and objective sleep duration.This was a cross-sectional study. Study participants were community-dwelling caregivers of spouses with dementia (n = 122) and noncaregivers (n = 53). A sleep duration discrepancy index was created by subtracting objective sleep duration measured with 3 consecutive 24-hour periods of actigraphy from self-reported sleep duration measured with the Pittsburgh Sleep Quality Index. Covariates included participants' demographic characteristics, depressive symptoms, positive and negative affects, personal mastery, and caregiving-role overload.Caregivers showed a greater discrepancy in sleep duration than did noncaregivers (-0.46 hour vs 0.22 hour, respectively;The findings suggest a potential mediating role of positive affect on the relationship between caregiving status and sleep duration discrepancy. As an aid for understanding the role of lower positive affect, use of actigraphy may help address sleep discrepancy in caregivers.Song Y, Moore RC, Jeste DV, et al. Discrepancy between self-reported and objective sleep duration among dementia caregivers and noncaregivers.

BACKGROUND Obstructive sleep apnea (OSA) is often comorbid with both substance use disorders (SUD) and posttraumatic stress disorder (PTSD), yet frequently goes undiagnosed and untreated. We present data on the feasibility and acceptability of objective OSA diagnosis procedures, findings on OSA prevalence, and the relationship between OSA and baseline SUD/PTSD symptoms among veterans in residential treatment for comorbid PTSD/SUD. METHODS Participants were 47 veterans admitted to residential PTSD/SUD treatment. Participants completed questionnaires assessing PTSD and sleep symptoms, and filled out a sleep diary for seven days. Apnea-hypopnea index (AHI) was recorded using the overnight Home Sleep Apnea test (HSAT; OSA was diagnosed with AHI ≥ 5). RESULTS Objective OSA diagnostic testing was successfully completed in 95.7% of participants. Of the 45 veterans who went through HSAT, 46.7% had no OSA, 35.6% received a new OSA diagnosis, and 8.9% were previously diagnosed with OSA and were using positive airway pressure treatment (PAP); an additional 8.9% were previously diagnosed with OSA, reconfirmed with the HSAT, but were not using PAP. One hundred percent of respondents during follow-up deemed the testing protocol's usefulness as "Good" or "Excellent." CONCLUSION OSA diagnostic testing on the residential unit was feasible and acceptable by participants and was effective in diagnosing OSA. OSA testing should be considered for everyone entering a SUD and PTSD residential unit. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

STUDY OBJECTIVES: To evaluate the clinical utility of actigraphy as compared with sleep questionnaires prior to the Multiple Sleep Latency Test (MSLT) in a sleep disorders clinic population. METHODS: Twenty-eight clinically referred participants (mean age: 42.3 ± 18.8 years) completed the study protocol. On day 1, participants completed the following questionnaires: Epworth Sleepiness Scale (ESS), Insomnia Severity Index, Pittsburgh Sleep Quality Index (PSQI), Visual Analog Scale (affect, vigor), Patient Health Questionnaire, and Multidimensional Fatigue Symptom Inventory–Short Form. On days 1–8, participants wore an actigraph and completed a sleep diary to assess mean nighttime and mean daytime total sleep time and sleep efficiency or sleep percentage. On day 9, participants repeated the ESS and completed an MSLT. Correlations assessed mean MSLT sleep-onset latency (MSLT-SOL) vs actigraphy, sleep diary, and questionnaires. Chi-square analyses assessed abnormal MSLT-SOL (≤ 8 minutes) or daytime sleepiness (ESS ≥ 10) and referral question (ie, sleep-disordered breathing vs hypersomnolence disorder). RESULTS: Mean MSLT-SOL was correlated with nighttime total sleep time assessed via both actigraphy and diary, but not with questionnaires. Significant correlations emerged for ESS score on day 1 vs 9, actigraphy vs sleep diary mean nighttime total sleep time, and PSQI vs mean sleep diary sleep efficiency. There was no significant relationship between mean MSLT-SOL and referral question. CONCLUSIONS: Our finding that total sleep time measured by actigraphy was associated with MSLT-SOL suggests it is useful in informing the interpretation of MSLT findings; however, it does not appear to be a viable substitute for MSLT for the measurement of objective sleepiness in clinical settings. CITATION: Kelly MR, Zeidler MR, DeCruz S, et al. Actigraphy prior to Multiple Sleep Latency Test: nighttime total sleep time predicts sleep-onset latency. J Clin Sleep Med. 2022;18(1):161–170.

PURPOSE: Optimal cognitive performance might prevent vehicle accidents. Identifying time-related circadian and homeostatic parameters having an impact on cognitive performance of drivers may be crucial to optimize drivers’ performance. METHODS: In this prospective study conducted on bus drivers, two drivers alternated driving during a 24-h round trip and were accompanied by an interviewer. Each driver was tested using Karolinska Sleepiness Scale (KSS) and the reversed digit span Wechsler Working Memory test before the start of his shift and then every 6 h during a “work/driving” day. Psychomotor Vigilance Task (PVT) was assessed before and after the journey. Linear mixed model was used to explore the factors affecting cognitive performance and sleepiness in univariate and multivariate analysis. RESULTS: Among 35 bus drivers, the effect of time of day on working memories was statistically significant (p = 0.001), with the lowest working memory scores at 04:00 am (± 1). The highest score of subjective sleepiness was also at 04:00 am (± 1). The time on task parameter affected sleepiness significantly (p = 0.024) and sleepiness was significantly associated with decreased working memory. Psychomotor Vigilance Task reaction time mean and the number of minor lapses were significantly increased after the journey, which suggested decreased vigilance. In multivariable analysis, a longer interval between the beginning of working hours and testing time (B (95% CI) = 15.25 (0.49 to 30), p = 0.043) was associated with higher (i.e., slower) PVT reaction time mean. CONCLUSIONS: These results suggest that optimizing bus drivers’ working schedules may improve drivers’ sleepiness and cognitive performance and thus increase road safety.

BackgroundWrist-worn actigraphy can objectively measure sleep, and has advantages over self-report, particularly for people with Bipolar Disorder (BD) for whom self-reports might be influenced by affect. Clinically useful data reduction approaches are needed to explore these complex data.MethodsWe created a composite score of sleep metrics in BD based on 51 BD and 80 healthy comparison (HC) participants. Subjects wore an actigraph for up to 14 consecutive 24-h periods, and we assessed total sleep time (TST), wake after sleep onset (WASO), percent sleep (PS), and number of awakenings (NA). We focused on participants who had at least 5 nights of actigraphy data. We computed z-scores for within-person means of sleep measures for BD subjects versus HCs, which were averaged to create a composite measure. We correlated this composite with participant characteristics, and used LASSO regression to identify sleep measures best explaining variability in identified correlates.ResultsSleep measures and the composite did not differ between BDs and HCs; however, there was considerable variability in z-scores among those with BD. In BDs, the composite score was higher in women (t(49)=2.28, p=0.027) and those who were employed (t(34)=2.34, p=0.025), and positively correlated with medication load (r=0.41, p=0.003) while negatively correlated with Young Mania Rating Scale (YMRS; r=-0.35, p=0.030). In LASSO regression, TST and NA best explained medication load while PS best explained employment and YMRS.ConclusionWhile a composite score of sleep metrics may provide useful information about sleep quality globally, our findings suggest that selection of theory-driven sleep measures may be more clinically meaningful.

Patients who have undergone hematopoietic stem cell transplant (HSCT) may experience cognitive impairment that can persist after treatment. Several studies have shown that bright light therapy may improve cognition, potentially due to its effects on the circadian system via brain regions that respond preferentially to light. In this double-blind randomized controlled trial, the efficacy of bright light therapy on cognition was examined in HSCT survivors. Forty-seven HSCT survivors at an urban hospital in the United States were screened for mild cognitive impairment, randomized to either bright white light (BWL) or comparison dim red light (DRL) conditions using a block randomization approach, and instructed to use their assigned light box every morning upon awakening for 30 min for 4 weeks. Assessments occurred at baseline, the end of the second week of the intervention, the end of the intervention, and at follow-up (8 weeks later). The primary outcome was objective cognitive function as measured by a global composite score on neuropsychological tests. Secondary outcomes included cognitive performance in individual domains, self-reported cognitive function, fatigue, sleep and sleep quality, and circadian rhythm robustness. Repeated-measures linear mixed models for both objective and self-reported cognitive function indicated significant main effects for time ( ps < 0.05) suggesting significant improvements in both conditions over time. Time by light condition interaction effects were not significant. Models focused on secondary outcomes yielded no significant effects. Both BWL and DRL groups demonstrated significant improvements in objective cognitive and self-reported cognitive function over time, but there was no hypothesized effect of BWL over DRL nor associations with circadian rhythm robustness. Therapeutic effects of both light conditions, practice effects, and/or placebo effects may account for the findings. Trial registration: ClinicalTrials.gov Identifier: NCT02677987 (9 February 2016)

Background Older men with the worse alignment of activity and light may have lower levels of cognition and increased rates of cognitive decline. Methods This cohort consisted of 1 036 older men (81.1 ± 4.6 years) from the MrOS Sleep Study (2009–2012). Light and activity levels were gathered by wrist actigraphy. Phasor analysis was used to quantify the alignment of light–dark and rest-activity patterns (magnitude) and their temporal relationship (angle). Global cognitive function (Modified Mini-Mental State examination [3MS]) and executive function (Trails B test) were measured, then repeated 4.2 ± 0.8 years later. Linear regression models examined the associations of phasor magnitude and angle with cognition and cognitive decline. Models were adjusted for age, clinic, race, education, and season. Results Smaller phasor magnitude (worse aligned light and activity patterns) was associated with lower initial level and increased decline in executive function. Compared to those with higher phasor magnitude, those with lower magnitude took an average of 11.1 seconds longer to complete the Trails B test (quartile 1 vs quartile 4, p = .02). After follow-up, Trails B completion time increased an average of 5.5 seconds per standard deviation decrease in phasor magnitude (95% confidence interval [CI] 0.7–10.4, p = .03). There were no associations with phasor angle, and none with magnitude and global cognition (3MS). Conclusion Among older men, worse alignment of light and activity patterns was associated with worse initial performance and increased decline in executive function, but not related to global cognition. Interventions that improve the alignment of light and activity may slow cognitive decline in older adults.

STUDY OBJECTIVES: Depression is prevalent among patients with sleep disorders, and studies show associations between suicidal ideation and insufficient sleep. Using retrospective clinic records, we examined positive depression screening rates among adolescent sleep clinic patients relative to other subspecialty clinic patients. We also examined relationships between sleep diagnoses and positive depression screening rate in adolescent sleep clinic patients. METHODS: Data were analyzed from patients ages 12–18 (n = 12,520) who were screened for depression using the Patient Health Questionnaire-2 (PHQ-2). Those who screened positive were administered the PHQ-9. Logistic regression was used to examine effects of age, sex, race, ethnicity, and clinic on likelihood of a positive depression screen. Within sleep clinic patients (n = 308), demographic factors, sleep disorder diagnosis, and body mass index percentile were examined using logistic and linear regression. RESULTS: Among all patients screened, older age and female sex predicted positive depression screens. Sleep clinic patients were more likely to screen positive than patients in 9 other clinics [odds ratios 2.03–6.83]. Results were similar even when the PHQ-9 sleep item was excluded [odds ratios 2.18–6.41]. Within sleep clinic patients, sleep disorder diagnosis (eg, insomnia, obstructive sleep apnea) was predictive of a positive depression screen (χ(2)(1) = 10.88, P = .004): insomnia patients were most likely to be experiencing depression. CONCLUSIONS: Adolescent sleep clinic patients are at increased risk for depressive symptoms. Among insomnia patients, risk was independent of age, sex, and obesity, suggesting a unique relationship between insomnia and affective distress, as has been found in adults. Assessing adolescents for sleep disorders should be prioritized, given the strong association with depression. CITATION: Inkelis SM, Ancoli-Israel S, Thomas JD, Bhattacharjee R. Elevated risk of depression among adolescents presenting with sleep disorders. J Clin Sleep Med. 2021;17(4):675–683.

Sleep disturbances are a key feature of bipolar disorder (BD), and poor sleep has been linked to mood symptoms. Recent use of ecological momentary assessment (EMA) has allowed for nuanced exploration of the sleep-mood link; though, the scale and directionality of this relationship is still unclear. Using EMA, actigraphy, and self-reported sleep measures, this study examines the concurrent and predictive relationships between sleep and mood. Participants with BD (n=56) wore actigraphy devices for up to 14 days and completed validated scales and daily EMA surveys about mood and sleep quality. Linear mixed models were used to examine overall and time-lagged relationships between sleep and mood variables. EMA mood ratings were correlated with validated rating scales for depression, mania, anxiety, and impulsivity. Poor self-reported sleep quality was associated with worse overall ratings of sadness and anger. Worse self-reported sleep quality was associated with greater sadness the following day. Higher daytime impulsivity was associated with worse sleep quality the following night. Exploratory analyses found relationships between worse and more variable mood (sadness, anger, and impulsivity) with worse and more variable sleep that evening (efficiency, WASO, and sleep onset time). The sample size was modest, fairly homogenous, and included mainly euthymic persons with BD. EMA-based assessments of mood and sleep are correlated with validated scale scores and provide novel insight into intra-individual variability. Further work on the complex two-way interactions between sleep and mood is needed to better understand how to improve outcomes in BD.

Premature mortality and increased physical comorbidity associated with bipolar disorder (BD) may be related to accelerated biological aging. Sleep disturbances and inflammation may be key mechanisms underlying accelerated aging in adults with BD. To our knowledge, these relationships have not been examined rigorously. This cross-sectional study included 50 adults with BD and 73 age- and sex-comparable non-psychiatric comparison (NC) subjects, age 26–65 years. Participants were assessed with wrist-worn actigraphy for total sleep time (TST), percent sleep (PS), and bed/wake times for 7 consecutive nights as well as completing scales for subjective sleep quality. Within-individual variability in sleep measures included intra-individual standard deviation (iSD) and atypicality of one evening's sleep. Blood-based inflammatory biomarkers included interleukin (IL)-6, C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α). Linear regression analyses tested relationships of mean and iSD sleep variables with inflammatory marker levels; time-lagged analyses tested the influence of the previous evening's sleep on inflammation. BD participants had worse subjective sleep quality, as well as greater TST iSD and wake time iSD compared to the NC group. In all participants, higher TST iSD and lower mean PS were associated with higher IL-6 levels (p = 0.04, ηp2 = 0.042; p = 0.05, ηp2 = 0.039, respectively). Lower mean PS was associated with higher CRP levels (p = 0.05, ηp2 = 0.039). Atypicality of the previous night's TST predicted next day IL-6 levels (p = 0.05, ηp2 = 0.04). All of these relationships were present in both BD and NC groups and remained significant even after controlling for sleep medications. Overall, sleep measures and their variability may influence inflammatory markers in all adults. Thus, sleep may be linked to the inflammatory processes believed to underlie accelerated aging in BD.

Background The increasing prevalence of Alzheimer’s Disease (AD) and lack of effective medications has led to a need to identify modifiable risk factors as targets for interventions. In this cross-sectional study, we sought to determine whether worse sleep quality is associated with increased pathological tau, and whether this relationship is affected by amyloid pathology. Methods 66 male participants underwent Florbetapir (AV45) Positron Emission Tomography (PET), Flortaucipir (FTP) PET and completed the Pittsburgh Sleep Quality Index questionnaire (PSQI) as part of the Department of Defense Alzheimer’s Disease Neuroimaging Initiative, a multicenter study collecting data from Vietnam War veterans, some of whom have a history of Post-Traumatic Stress Disorder (PTSD), or non-penetrating Traumatic Brain Injury (TBI). AV45 PET was used to determine the presence of significant amyloid pathology, and t-tests were used to assess differences in tau deposition in Braak regions associated with AD progression between amyloid positive and amyloid negative individuals. We used regression models to determine the effects of amyloid pathology and PSQI on tau deposition in Braak regions. Results Among the 66 participants, the average (SD) age was 71.04 (0.99) years. 14 individuals were amyloid positive (21%), and 52 were amyloid negative (79%). The amyloid positive and amyloid negative groups did not differ in tau in the regions investigated. There were no significant main effects of amyloid status or PSQI on FTP Standardized Uptake Value ratio (SUVr) in any of the regions investigated. However, in Braak stages III-IV, there was a significant interaction of amyloid status on PSQI (β = 0.039, p = 0.035) with higher PSQI correlating with higher FTP SUVr in amyloid-positive individuals only (β = 0.031, p = 0.017). Conclusions Our study found that an AD profile of tau deposition was associated with an interaction between self-reported sleep quality and amyloid pathology such that worse self-reported sleep was related to higher tau in regions associated with AD progression, but only in individuals with high cerebral amyloid deposition. Our study suggests that sleep quality may be a modifiable risk factor in preclinical and prodromal populations of AD.

OBJECTIVE Disruption of rest-activity rhythms is cross-sectionally associated with metabolic disorders, including type 2 diabetes, yet it remains unclear whether it predicts impaired glucose metabolism and homeostasis. The aim of this study is to examine the cross-sectional and prospective associations between rest-activity rhythm characteristics and glycemic measures in a cohort of older men. RESEARCH DESIGN AND METHODS Baseline rest-activity rhythms were derived from actigraphy with use of extended cosine model analysis. With subjects fasting, glucose, insulin, and HOMA of insulin resistance (HOMA-IR) were measured from blood at baseline and after ∼3.5 years. Type 2 diabetes was defined based on self-report, medication use, and fasting glucose. RESULTS In the cross-sectional analysis (n = 2,450), lower 24-h amplitude-to-mesor ratio (i.e., mean activity-adjusted rhythm amplitude) and reduced overall rhythmicity were associated with higher fasting insulin and HOMA-IR (all Ptrend < 0.0001), indicating increased insulin resistance. The odds of baseline type 2 diabetes were significantly higher among those in the lowest quartile of amplitude (Q1) (odds ratio [OR]Q1 vs. Q4 1.63 [95% CI 1.14, 2.30]) and late acrophase group (ORlate vs. normal 1.46 [95% CI 1.04, 2.04]). In the prospective analysis (n = 861), multiple rest-activity characteristics predicted a two- to threefold increase in type 2 diabetes risk, including a lower amplitude (ORQ1 vs. Q4 3.81 [95% CI 1.45, 10.00]) and amplitude-to-mesor ratio (OR 2.79 [95% CI 1.10, 7.07]), reduced overall rhythmicity (OR 3.49 [95% CI 1.34, 9.10]), and a late acrophase (OR 2.44 [1.09, 5.47]). CONCLUSIONS Rest-activity rhythm characteristics are associated with impaired glycemic metabolism and homeostasis and higher risk of incident type 2 diabetes.

Background This study examined whether biological mechanisms linking dementia caregiving with an increased risk of coronary heart disease can be modified by psychosocial interventions and which caregivers might benefit the most from an intervention. Methods Spousal dementia caregivers were randomized to 12-week treatment with either a behavioral activation intervention (ie, Pleasant Events Program [PEP]; n = 60), or an active control Information and Support (IS; n = 63) condition. Indicators of caregiving stress were assessed pretreatment and circulating cardiovascular biomarkers were measured pre- and posttreatment. Results There were no significant changes in biomarker levels from pre- to posttreatment both by treatment condition and across all caregivers. Regardless of the treatment condition, exploratory regression analysis revealed that caregivers were more likely to show significant decreases in C-reactive protein (CRP) and D-dimer when their spouse had severe functional impairment; in interleukin (IL)-6 and CRP when they had greater distress due to care recipient’s problem behaviors; in tumor necrosis factor (TNF)-α when they had higher levels of negative affect; and in IL-6, CRP, TNF-α, and D-dimer when they had higher personal mastery. Within the PEP group, caregivers with higher negative affect and those with higher positive affect were more likely to show a reduction in von Willebrand factor and D-dimer, respectively. Within the IS group, caregivers whose spouse had severe functional impairment were more likely to show a decrease in IL-6. Conclusions Unlike the average caregiver, caregivers high in burden/distress and resources might benefit from psychosocial interventions to improve cardiovascular risk, although these observations need confirmation.

Purpose To examine long-term cognitive effects of chemotherapy and identify predictors among women with breast cancer (WBC). Patients and methods Sixty-nine WBC scheduled to receive chemotherapy, and 64 matched-controls with no cancer, participated. Objective and subjective cognition, total sleep time, nap time, circadian activity rhythms (CAR), sleep quality, fatigue, and depression were measured pre-chemotherapy (Baseline), end of cycle 4 (Cycle-4), and one-year post-chemotherapy (1-Year). Results WBC showed no change in objective cognitive measures from Baseline to Cycle-4 but significantly improved from both time points to 1-Year. Matched-controls showed an increase in test performance at all time points. WBC had significantly higher self-reported cognitive dysfunction at Cycle-4 and 1-Year compared to baseline and compared to matched-controls. Worse neuropsychological functioning was predicted by less robust CARs (i.e., inconsistent 24 h pattern), worse sleep quality, longer naps, and worse cognitive complaints. Worse subjective cognition was predicted by lower sleep quality and higher fatigue and depressed mood. Conclusion Objective testing showed increases in performance scores from pre- and post-chemotherapy to one year later in WBC, but matched-controls showed an increase in test performance from baseline to Cycle-4 and from Cycle-4 to 1-Year, likely due to a practice effect. The fact that WBC showed no practice effects may reflect a form of learning deficit. Compared with the matched-controls, WBC reported significant worsened cognitive function. In WBC, worse objective and subjective cognitive functioning were predicted by worse sleep and sleep-related behaviors (naps and CAR). Interventions that target sleep, circadian rhythms, and fatigue may benefit cognitive function in WBC.

Background Sleep disturbances are associated with risk of cognitive decline but it is not clear if treating disturbed sleep mitigates decline. We examined differences in cognitive trajectories before and after sleep treatment initiation. Method Data came from the 2006–2014 Health and Retirement Study (HRS). At each of 5 waves, participants were administered cognitive assessments and scores were summed. Participants also reported if, in prior 2 weeks, they had taken medications or used other treatments to improve sleep. Our sample (N = 3 957) included individuals who at HRS 2006 were 50 years and older, had no cognitive impairment, reported no sleep treatment, and indicated experiencing sleep disturbance. We identified differences between those receiving versus not receiving treatment in subsequent waves and, among those treated (n = 1 247), compared cognitive trajectories before and after treatment. Results At baseline, those reporting sleep treatment at subsequent waves were more likely to be younger, female, Caucasian, to have more health conditions, to have higher body mass index, and more depressive symptoms (all ps ≤ .015). Decline in cognitive performance was mitigated in periods after sleep treatment versus periods before (B = −0.20, 95% CI = [−0.25, −0.15], p < .001 vs B = −0.26, 95% CI = [−0.32, −0.20], p < .001), and this same trend was seen for self-initiated and doctor-recommended treatments. Trends were driven by those with higher baseline cognitive performance—those with lower performance saw cognitive declines following sleep treatment. Conclusions In middle-aged and older adults with sleep disturbance, starting sleep treatment may slow cognitive decline. Future research should assess types, combinations, and timing of treatments most effective in improving cognitive health in later life.

Introduction Since the use of sleep-promoting drugs can also lead to residual morning sleepiness, it is important to determine if a new hypnotic is associated with such a carryover effect of treatment. To this end, an assessment of sleepiness/alertness was included in lemborexant (LEM) phase 3 studies. LEM is a competitive dual orexin receptor antagonist approved in several countries for the treatment of adults with insomnia. This post-hoc analysis of Study 304 (E2006-G000-304; NCT02783729) assessed the impact of LEM on morning sleepiness/alertness in subjects who reported at least mild/moderate morning sleepiness at baseline. Methods Study 304 was a randomized controlled study in adults ≥55y with insomnia disorder (N=1006). Subjects received bedtime doses of placebo (PBO), LEM 5mg (LEM5), LEM 10mg (LEM10), or zolpidem tartrate extended release 6.25 mg (not reported here) for 1 month. A daily Sleep Diary assessed morning sleepiness, within 90 min of waketime, with the question “How alert/sleepy do you feel this morning?” rated from 1 (extremely sleepy) to 9 (extremely alert). Scores were averaged over 7-day periods for baseline (single-blind run-in) and first and last 7 days of treatment. Chi-square tests were used to compare the shift from sleepy (≤3) to more alert (>3) between PBO and treatment groups. Results At baseline, 59/203 (29.1%), 66/261 (25.3%), and 79/265 (29.8%) of the PBO, LEM5, and LEM10 subjects reported a score ≤3, indicating at least mild/moderate morning sleepiness. At the end of 1 month of treatment, 37/57 (64.9%) of the PBO subjects rated themselves as less sleepy and more alert (>3), compared with 50/64 (78.1%; P=0.11) LEM5- and 58/76 (76.3%; P=0.15) LEM10-treated subjects. Conclusion In this study, ~28% of subjects reported morning sleepiness at baseline. More subjects who reported sleepiness at baseline and received LEM reported improved morning alertness during the last week of treatment compared with PBO subjects. These data are concordant with previous findings of a lack of effect of LEM on tasks requiring alertness in the morning. Support (if any) Eisai Inc.

Introduction Obstructive sleep apnea (OSA) is common in older adults and has recently been implicated in pathogenesis of Alzheimer’s disease (AD). Sleep disruption is a possible reversible cause of memory impairment. Furthermore, quality of sleep has been determined to be one of the most important variables affecting overnight memory consolidation. Men and women differ in frequency and type of sleep complaints. As part of a larger study, data are presented on sex-stratified correlations between sleepiness and sleep-dependent memory consolidation in cognitively normal older adults with OSA. Methods Forty-Three participants (age 65 to 81 years; M=70.5 years, SD=4.3) deemed cognitively normal based on a Montreal Cognitive Assessment [MOCA] score of >26 were analyzed. The sample was 48.9% women; 86% White; 90.7% Non-Hispanic; and 73.8% with a bachelor's degree or higher. The Epworth Sleepiness Scale (ESS) was used to assess general daytime sleepiness. Sleep-dependent memory consolidation was assessed using the Word-pairs Association (WPA) task. The WPA task shows a word pair for 5 seconds for the participant to learn and the next morning, post-sleep, the delayed recognition test is performed. Results Preliminary descriptive analyses revealed women had an average ESS of 5.4 (SD=3.0) and WPA score of 29.6 (SD=4.3); while men had an average ESS of 6.9 (SD=2.99) and WPA of 29.5 (SD=7.4). Non-parametric correlations, assessed to examine the association between ESS sum scores and WPA scores, revealed a significant negative correlation between ESS and WPA for female sex, but not for male sex. That is, in women, greater daytime sleepiness scores were associated with worse sleep-dependent memory consolidation (r=-.66, p= .01). Conclusion Preliminary findings of the ongoing study provide support for a sex specific association between daytime sleepiness and sleep-dependent memory consolidation. Further research on this topic is needed to determine optimal preventative strategies for older adults at risk of cognitive decline. Support (if any) 1R01AG063925-01A1 provided by National Institute on Aging

Despite the growing use of home sleep testing for obstructive sleep apnea (OSA), there are significant barriers that make it difficult for patients. This study aimed to evaluate a new set of wireless patches for the detection of OSA as compared to polysomnography (PSG) respiratory signals. Safety was also evaluated.Patients (n = 25; mean age = 51.3; SD = 15.6) undergoing standard PSG evaluation for OSA wore 2 device patches applied on the chest and abdomen to provide surrogates of respiratory effort and derived airflow. Two sets of respiratory data (with common SpO2 and heart rate as a reference from PSG) were created, one from PSG and one from the device patches. Data were scored by a Registered Polysomnographic Technologist. Linear regression analyses and Bland-Altman plots were used to compare the two derived apnea-hypopnea indices (AHI). Bench testing was performed to determine whether the device patch respiratory signal accuracy remained consistent for different body characteristics.There was a significant correlation for AHI between the device patch and PSG (r = 0.979; P.001; 95% CI 0.952, 1.00). There were also significant correlations between PSG and the device patch for supine AHI (r = 0.866, P.001, 95% CI 0.610, 0.965) and nonsupine AHI (r = 0.983;0.001, 95% CI 0.954, 1.00). No differences in respiratory signal accuracy were found with bench testing comparison groups.These preliminary results suggest that the device patch may be an effective way to measure respiratory dynamics, including derived airflow, to evaluate OSA. Results show promise as a new innovative method for home sleep testing.

Simple SummaryCancer-related fatigue (CRF) is one of the most frequently reported symptoms with prevalence rates of 25 to 60 percent in (non-)Hodgkin lymphoma survivors. Several (pilot) studies showed promising effects of light therapy to reduce CRF. The aim of the current study is to evaluate the short- and long-term efficacy of light therapy on CRF and associated symptoms in chronically fatigued (non-)Hodgkin lymphoma survivors. Eighty-three survivors were exposed to bright white light (intervention) and another 83 survivors were exposed to dim white light (comparison). Results showed that all participants, irrespective of light condition, reported reduced levels of fatigue after the completion of light therapy. Similar results were found for depression, sleep quality, and some aspects of quality of life. No effect was found on circadian rhythms or objectively assessed sleep. Therefore, it is important to further investigate which aspects of intervention are associated with the improvements observed after light therapy.Purpose: To evaluate the short- and long-term effects of light therapy on fatigue (primary outcome) and sleep quality, depression, anxiety, quality of life, and circadian rhythms (secondary outcomes) in survivors of (non-)Hodgkin lymphoma presenting with chronic cancer-related fatigue. Methods: We randomly assigned 166 survivors (mean survival 13 years) to a bright white light intervention (BWL) or dim white light comparison (DWL) group. Measurements were completed at baseline (T0), post-intervention (T1), at three (T2), and nine (T3) months follow-up. A mixed-effect modeling approach was used to compare linear and non-linear effects of time between groups. Results: There were no significant differences between BWL and DWL in the reduction in fatigue over time. Both BWL and DWL significantly (p < 0.001) improved fatigue levels during the intervention followed by a slight reduction in this effect during follow-up (EST0-T1 = -0.71; EST1-T3 = 0.15). Similar results were found for depression, sleep quality, and some aspects of quality of life. Light therapy had no effect on circadian rhythms. Conclusions: BWL was not superior in reducing fatigue compared to DWL in HL and DLBCL survivors. Remarkably, the total sample showed clinically relevant and persistent improvements on fatigue not commonly seen in longitudinal observational studies in these survivors.

Associations between subjective maternal bonding recalled from the first 16 years of life and current sleep indices were investigated in a clinical sample of 34 adults with major depressive disorder and 36 normal controls (N = 70) using the self-report Parental Bonding Instrument and wrist actigraphy. Results of multiple linear regression analyses indicated that reports of maternal bonding indices were associated with several sleep indices in adulthood independent of depression status. Higher levels of maternal care were associated with greater time in bed (TIB) and total sleep time (TST). Higher levels of maternal overprotection were associated with fewer awakenings. Findings indicate that reported maternal bonding characteristics in childhood are related to objectively measured sleep characteristics in adulthood, independent of mood state.

Background/objective Nocturia's impact on sleep causes significant burden for patients. This study aimed to develop a novel patient-reported outcome (PRO) measure, the Nocturia Sleep Quality Scale (NSQS), for the assessment of the impact of nocturia (defined as ≥2 nocturnal voids/night) on sleep. Methods Sleep-related concepts were identified through a targeted literature review, after which in-depth concept elicitation interviews with patients with a clinical diagnosis of nocturia were conducted. Draft items were generated to address concepts identified as important, meaningful, and relevant. Items were further refined through three iterative sets of cognitive debriefing interviews to optimize instructions, question wording, and response options. Two sleep research experts also provided input. Results The literature review and data from 18 concept elicitation interviews provided the basis for a comprehensive set of concepts. Constant comparative analysis was used to identify themes and support item development. The draft questionnaire consisted of 14 items with item-specific response scales. Wording and scaling of the items was optimized based on feedback from the 22 cognitive debriefing interviews and expert input. The results confirmed the completeness and relevance of the NSQS, providing support for the content validity and ability of items to reflect patient perception of nocturia-related sleep impacts. Conclusions The 6-item NSQS assesses the impact of nocturia on sleep by evaluating nighttime awakenings, sleep quantity, and sleep quality. The NSQS is self-administered and is intended to assess change in nocturia's impact on sleep after treatment in a standardized manner. Psychometric evaluation is under way to describe key measurement properties.

Author(s): Harrison, Elizabeth M; Yablonsky, Abigail M; Powell, Alexandra L; Ancoli-Israel, Sonia; Glickman, Gena L | Abstract: BackgroundLight is the primary synchronizing cue for the circadian timing system, capable of exerting robust physiological effects, even with very dim and/or brief photic exposure. Mammals, including humans, are particularly susceptible to light at night. As such, measures of light in the sleeping environment are critical for evaluating sleep health. Sleep diaries provide inexpensive measures of sleep, but do not typically include light information.MethodsFour questions probing visual perception of light in the bedtime and waking environments were added to the Consensus Sleep Diary for Morning administration. As part of a lighting intervention study, 18 hospital Labor and Delivery Department personnel completed the sleep diary for 1 week in each of two experimental conditions while wearing Actiwatch devices equipped with photosensors. Diary responses were evaluated against photosensor values from the beginning and end of each rest interval (n=194 rest intervals), as well as against sleep measures, utilizing linear mixed models.ResultsResponses to light questions were related to actual light measures at bedtime, controlling for shift type and experimental condition. In addition, subjective light information at bedtime and waking was related to both objective and subjective sleep parameters, with data generally indicating poorer sleep with light in the sleeping environment.ConclusionQuestions addressing perception of light in the sleeping environment may provide a crude yet affordable metric of relative photic intensity. Further, as responses relate to sleep outcomes, subjective light information may yield valuable insights regarding mechanisms and outcomes of clinical significance in sleep and circadian research.

Altered 24-hour rest–activity rhythms may be associated with cognitive impairment in older adults, but evidence from prospective studies is limited. Nonparametric methods were used to assess actigraphy-based activity patterns in 2 496 older men. Incident cognitive impairment was assessed 4 times over 12 years using the Modified Mini-Mental State Examination (3MS) and Trails B tests, self-reported medication use, and clinical diagnosis. The highest quartile (vs the lowest) of intradaily variability and the lowest quartiles (vs the highest) of interdaily stability and relative amplitude were associated with incident cognitive impairment (hazard ratio [95% confidence interval]: 1.82 [1.31–2.53], 1.36 [0.99–1.86], and 1.85 [1.33–2.56], respectively). A larger increase in intradaily variability over 7.5 years was associated with a greater subsequent decline in 3MS scores but not in Trails B performance. In conclusion, less stable and more variable rest–activity rhythms may represent early biomarkers of cognitive impairment in older men.

Actigraphy can objectively measure sleep in studies on Bipolar Disorder (BD) where subjective sleep ratings might be influenced by affect. Actigraphy data are complex necessitating data reduction approaches. We created a composite score of actigraphy sleep metrics (total sleep time [TST], wake after sleep onset [WASO], and percent sleep [PS]) in BD. We computed z-scores of sleep measures for n=51 BD vs. n=80 healthy subjects and averaged scores. We examined associations with participant characteristics and used LASSO to identify metrics best explaining composite variability. Higher composite scores (better sleep) were seen in employed vs. unemployed (t=2.40, df=34, p=0.02), and correlated with higher medication load (r=0.41, p=0.004), lower mania symptomatology (r=-0.33, p=0.04) and lower interleukin (IL)-6 levels (r=-0.32, p=0.02). TST best explained variability in medication load and PS best explained employment, mania symptoms and IL-6. Given observed specificity of associations, selecting theory-driven sleep metrics may be more appropriate than a composite.

To examine long-term cognitive effects of chemotherapy and identify predictors among women with breast cancer (WBC).Sixty-nine WBC scheduled to receive chemotherapy, and 64 matched-controls with no cancer, participated. Objective and subjective cognition, total sleep time, nap time, circadian activity rhythms (CAR), sleep quality, fatigue, and depression were measured pre-chemotherapy (Baseline), end of cycle 4 (Cycle-4), and one-year post-chemotherapy (1-Year).WBC showed no change in objective cognitive measures from Baseline to Cycle-4 but significantly improved from both time points to 1-Year. Matched-controls showed an increase in test performance at all time points. WBC had significantly higher self-reported cognitive dysfunction at Cycle-4 and 1-Year compared to baseline and compared to matched-controls. Worse neuropsychological functioning was predicted by less robust CARs (i.e., inconsistent 24 h pattern), worse sleep quality, longer naps, and worse cognitive complaints. Worse subjective cognition was predicted by lower sleep quality and higher fatigue and depressed mood.Objective testing showed increases in performance scores from pre- and post-chemotherapy to one year later in WBC, but matched-controls showed an increase in test performance from baseline to Cycle-4 and from Cycle-4 to 1-Year, likely due to a practice effect. The fact that WBC showed no practice effects may reflect a form of learning deficit. Compared with the matched-controls, WBC reported significant worsened cognitive function. In WBC, worse objective and subjective cognitive functioning were predicted by worse sleep and sleep-related behaviors (naps and CAR). Interventions that target sleep, circadian rhythms, and fatigue may benefit cognitive function in WBC.

Study Objectives Disrupted daily rhythms are associated with mild cognitive impairment (MCI) and dementia. The specific nature of how rhythms and cognition are related, however, is unknown. We hypothesized characteristics from a nonparametric estimate of circadian rest-activity rhythm patterns would be associated to the development of MCI or dementia. Methods Wrist actigraphy from 1232 cognitively healthy, community-dwelling women (mean age 82.6 years) from the Study of Osteoporotic Fractures was used to estimate rest-activity patterns, including intradaily variability (IV), interdaily stability (IS), most active 10-hour period (M10), least active 5-hour period (L5), and relative amplitude (RA). Logistic regression examined associations of these predictors with 5-year incidence of MCI or dementia. Models were adjusted for potential confounders. Results Women with earlier sleep/wake times had higher risk of dementia, but not MCI, (early vs. average L5 midpoint: OR, 1.66; 95% CI, 1.08–2.55) as did women with smaller day/night activity differentials (low vs. high RA: OR, 1.96; 95% CI, 1.14–3.35). IV, IS, and M10 were not associated with MCI or dementia. Conclusion The timing and difference in day/night amplitude, but not variability of activity, may be useful as predictors of dementia.

Chronic increases in pro-inflammatory cytokines in older adults, known as inflammaging, are an important risk factor for morbidity and mortality in the aging population. It has been suggested that circadian disruption may play a role in chronic inflammation, but there has been limited study that investigated the overall profile of 24-hour rest–activity rhythms in relation to inflammation using longitudinal data. In the Outcomes of Sleep Disorders in Older Men Study, we applied the extended cosine model to derive multiple rest–activity rhythm characteristics using multiday actigraphy, and examined their associations with 6 inflammatory markers (ie, C-reactive protein [CRP], interleukin 6 [IL-6], tumor necrosis factor alpha [TNF-α], tumor necrosis factor alpha soluble receptor II [TNF-α-sRII], interleukin-1β [IL-1β], interferon gamma [IFN-γ]) measured from fasting blood. We assessed both the cross-sectional association between rest–activity rhythms and inflammatory markers measured at baseline, and the prospective association between baseline rest–activity rhythms and changes in inflammatory markers over 3.5 years of follow-up. We found that multiple rest–activity characteristics, including lower amplitude and relative amplitude, and decreased overall rhythmicity, were associated with higher levels of CRP, IL-6, TNF-α, and TNF-α-sRII, but not IL-1β and IFN-γ at baseline. Moreover, the lowest quartile of these 3 rest–activity characteristics was associated with an approximately 2-fold increase in the odds of having elevated inflammation (ie, having 3 or more markers in the highest quartile) at baseline. However, we found little evidence supporting a relationship between rest–activity rhythm characteristics and changes in inflammatory markers. Future studies should clarify the dynamic relationship between rest–activity rhythms and inflammation in different populations, and evaluate the effects of improving rest–activity profiles on inflammation and related disease outcomes.

Objectives Persons with schizophrenia, and women in particular, are at high risk for sleep disturbances and inflammatory activation. The sleep-inflammation link has been reported to be stronger in women within the general population. This study sought to examine the sleep-inflammation link in persons with schizophrenia and its relationship with demographic, clinical and cognitive variables. Design Cross-sectional case-control study. Participants Community-dwelling outpatients with schizophrenia (N=144, 46% women) and non-psychiatric comparison (NC) participants (N=134, 52% women), age 26-65 years. Measurements Reported sleep disturbances (sleep quality and duration), and mental and physical health were assessed. Cognitive assessments included executive functioning (Delis-Kaplan Executive Function System) and global cognitive functioning (Telephone Interview for Cognitive Status - modified.) Inflammatory biomarkers included pro-inflammatory cytokines [high sensitivity C-Reactive Protein (hs-CRP), Interleukin (IL)-6, Tumor Necrosis Factor-α (TNF-α)] and an anti-inflammatory cytokine (IL-10). Results The schizophrenia group had longer sleep duration, worse sleep quality, and increased levels of hs-CRP, IL-6, and TNF-α compared to NCs. Women with schizophrenia were less likely to have good sleep quality and had elevated levels of hs-CRP and IL-6 compared to men with schizophrenia. In the schizophrenia group, worse sleep quality and global cognitive functioning were associated with higher hs-CRP and IL-6 levels. Female sex and younger age were also associated with higher hs-CRP levels. Conclusions Sleep disturbances and increased inflammation, which were common in schizophrenia, were associated in persons with schizophrenia. Moreover, women with schizophrenia had worse sleep quality and inflammation than men. Further examination of the sleep-inflammation links, their contribution to clinical outcomes, and sex-specific factors is warranted.

Study Objectives To estimate the association of self-reported poor sleep in multiple dimensions with health care costs in older men. Methods Participants were 1,413 men (mean [SD] age 76.5 [5.7] years) enrolled in both the Outcomes of Sleep Disorders in Older Men (MrOS Sleep) study and Medicare Fee-for-Service. Poor sleep was characterized at the baseline MrOS Sleep visit on five dimensions (satisfaction, daytime sleepiness, timing, latency, and duration). Health care costs and utilization were ascertained over 3 years of follow-up using Medicare Claims. Results Median (interquartile range [IQR]) annualized total health care costs (2018 US dollars) rose from $3,616 (IQR 1,523–7,875) for those with no impaired sleep dimensions to $4,416 (IQR 1,854–11,343) for men with two impaired sleep dimensions and $5,819 (IQR 1,936–15,569) for those with at least three impaired sleep dimensions. After multivariable adjustment, the ratio of total health care costs (CR) was significantly higher for men with two (1.24, 95% confidence interval [CI] 1.03– to 1.48) and men with at least three impaired sleep dimensions (1.78, 95% CI 1.42 to 2.23) vs. those with no impaired sleep dimensions. After excluding 101 men who died during the 3-year follow-up period, these associations were attenuated and not significant (CR 1.22, 95% CI 0.98 to 1.53 for men ≥3 impaired sleep dimensions vs. none). Conclusions Self-reported poor sleep on multiple dimensions is associated with higher subsequent total health care costs in older men, but this may be due to higher mortality and increased health care costs toward the end of life among those with poor sleep health.

Introduction To identify actigraphy sleep health profiles in older men (Osteoporotic Fractures in Men Study; N=2,640) and women (Study of Osteoporotic Fractures; N=2.430), and to determine whether the identified profiles predict mortality. Methods We applied a novel and flexible clustering approach (Multiple Coalesced Generalized Hyperbolic mixture modeling) to identify sleep health profiles based on actigraphy midpoint timing, midpoint variability, sleep interval length, continuity, and napping/inactivity. Adjusted Cox models were used to determine whether profile membership predicts time to all-cause mortality. Results We identified similar profiles with different prevalences in men and women: High Sleep Propensity [HSP] (20% of women; 39% of men; high napping and high continuity); Adequate Sleep [AS] (74% of women; 31% of men; average actigraphy levels); and Abnormal Continuity/Timing [ACT] (6% of women; 30% of men; low continuity and late/variable midpoint). In women, ACT was associated with increased mortality risk (Hazard Ratio [HR]=1.59 for ACT vs. AS; 1.75 for IS vs. HSP). In men, ACT and AS were associated with increased mortality risk relative to HSP (1.19 for IS vs. HSP; 1.22 for AS vs. HSP). Conclusion These findings suggest several considerations for sleep-related interventions in older adults. For instance, interventions may be developed to target the combination of low continuity with late/variable midpoint. Findings also indicate that high napping/inactivity co-occurs with high sleep continuity in some older adults. Although high napping/inactivity is typically considered a risk factor for deleterious health outcomes, our findings suggest that it may not be inherently problematic when occurring in combination with high sleep continuity. Support (If Any) The Osteoporotic Fractures in Men (MrOS) Study is supported by NIH grants U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, UL1 TR000128, R01 HL071194, R01 HL070848, R01 HL070847, R01 HL070842, R01 HL070841, R01 HL070837, R01 HL070838, and R01 HL070839. The Study of Osteoporotic Fractures (SOF) is supported by NIH grants R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576, and R01 AG026720. This study is also supported by NIH grants R01AG056331 and RF1AG056331 (PI: Wallace), R56AG065251 (PI: Lee), K01MH112683 (PI: Smagula), and R35HL135815 (PI: Redline).