Association of Rest-Activity Rhythm and Risk of Developing Dementia or Mild Cognitive Impairment in the Middle-Aged and Older Population: Prospective Cohort Study.

BACKGROUND: The relationship between 24-hour rest-activity rhythms (RARs) and risk for dementia or mild cognitive impairment (MCI) remains an area of growing interest. Previous studies were often limited by small sample sizes, short follow-ups, and older participants. More studies are required to fully explore the link between disrupted RARs and dementia or MCI in middle-aged and older adults. OBJECTIVE: We leveraged the UK Biobank data to examine how RAR disturbances correlate with the risk of developing dementia and MCI in middle-aged and older adults. METHODS: We analyzed the data of 91,517 UK Biobank participants aged between 43 and 79 years. Wrist actigraphy recordings were used to derive nonparametric RAR metrics, including the activity level of the most active 10-hour period (M10) and its midpoint, the activity level of the least active 5-hour period (L5) and its midpoint, relative amplitude (RA) of the 24-hour cycle [RA=(M10-L5)/(M10+L5)], interdaily stability, and intradaily variability, as well as the amplitude and acrophase of 24-hour rhythms (cosinor analysis). We used Cox proportional hazards models to examine the associations between baseline RAR and subsequent incidence of dementia or MCI, adjusting for demographic characteristics, comorbidities, lifestyle factors, shiftwork status, and genetic risk for Alzheimer's disease. RESULTS: During the follow-up of up to 7.5 years, 555 participants developed MCI or dementia. The dementia or MCI risk increased for those with lower M10 activity (hazard ratio [HR] 1.28, 95% CI 1.14-1.44, per 1-SD decrease), higher L5 activity (HR 1.15, 95% CI 1.10-1.21, per 1-SD increase), lower RA (HR 1.23, 95% CI 1.16-1.29, per 1-SD decrease), lower amplitude (HR 1.32, 95% CI 1.17-1.49, per 1-SD decrease), and higher intradaily variability (HR 1.14, 95% CI 1.05-1.24, per 1-SD increase) as well as advanced L5 midpoint (HR 0.92, 95% CI 0.85-0.99, per 1-SD advance). These associations were similar in people aged <70 and >70 years, and in non-shift workers, and they were independent of genetic and cardiovascular risk factors. No significant associations were observed for M10 midpoint, interdaily stability, or acrophase. CONCLUSIONS: Based on findings from a large sample of middle-to-older adults with objective RAR assessment and almost 8-years of follow-up, we suggest that suppressed and fragmented daily activity rhythms precede the onset of dementia or MCI and may serve as risk biomarkers for preclinical dementia in middle-aged and older adults.

Sleep and circadian biomarkers of postoperative delirium (SLEEP-POD): protocol for a prospective and observational cohort study.

INTRODUCTION: Surgical patients over 70 experience postoperative delirium (POD) complications in up to 50% of procedures. Sleep/circadian disruption has emerged as a potential risk factor for POD in epidemiological studies. This protocol presents a single-site, prospective observational study designed to examine the relationship between sleep/circadian regulation and POD and how this association could be moderated or mediated by Alzheimer's disease (AD) pathology and genetic risk for AD. METHODS AND ANALYSIS: Study staff members will screen for eligible patients (age ≥70) seeking joint replacement or spinal surgery at Massachusetts General Hospital (MGH). At the inclusion visit, patients will be asked a series of questionnaires related to sleep and cognition, conduct a four-lead ECG recording and be fitted for an actigraphy watch to wear for 7 days before surgery. Blood samples will be collected preoperatively and postoperatively and will be used to gather information about AD variant genes (APOE-ε4) and AD-related pathology (total and phosphorylated tau). Confusion Assessment Method-Scale and Montreal Cognitive Assessment will be completed twice daily for 3 days after surgery. Seven-day actigraphy assessments and Patient-Reported Outcomes Measurement Information System questionnaires will be performed 1, 3 and 12 months after surgery. Relevant patient clinical data will be monitored and recorded throughout the study. ETHICS AND DISSEMINATION: This study is approved by the IRB at MGH, Boston, and it is registered with the US National Institutes of Health on ClinicalTrials.gov (NCT06052397). Plans for dissemination include conference presentations at a variety of scientific institutions. Results from this study are intended to be published in peer-reviewed journals. Relevant updates will be made available on ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT06052397.

Associations Between Depression Symptom Burden and Delirium Risk: A Prospective Cohort Study.

Background and Objectives: Delirium and depression are prevalent in aging. There is considerable clinical overlap, including shared symptoms and comorbid conditions, including Alzheimer's disease, functional decline, and mortality. Despite this, the long-term relationship between depression and delirium remains unclear. This study assessed the associations of depression symptom burden and its trajectory with delirium risk in a 12-year prospective study of older hospitalized individuals. Research Design and Methods: A total of 319 141 UK Biobank participants between 2006 and 2010 (mean age 58 years [range 37-74, SD = 8], 54% women) reported frequency (0-3) of 4 depressive symptoms (mood, disinterest, tenseness, or lethargy) in the preceding 2 weeks prior to initial assessment visit and aggregated into a depressive symptom burden score (0-12). New-onset delirium was obtained from hospitalization records during 12 years of median follow-up. 40 451 (mean age 57 ±â€…8; range 40-74 years) had repeat assessment on average 8 years after their first visit. Cox proportional hazard models examined whether depression symptom burden and trajectory predicted incident delirium. Results: A total of 5 753 (15 per 1 000) newly developed delirium during follow-up. Increased risk for delirium was seen for mild (aggregated scores 1-2, hazards ratio, HR = 1.16, [95% confidence interval (CI): 1.08-1.25], p < .001), modest (scores 3-5, 1.30 [CI: 1.19-1.43], p < .001), and severe (scores ≥ 5, 1.38 [CI: 1.24-1.55], p < .001) depressive symptoms, versus none in the fully adjusted model. These findings were independent of the number of hospitalizations and consistent across settings (eg, surgical, medical, or critical care) and specialty (eg, neuropsychiatric, cardiorespiratory, or other). Worsening depression symptoms (≥1 point increase), compared to no change/improved score, were associated with an additional 39% increased risk (1.39 [1.03-1.88], p = .03) independent of baseline depression burden. The association was strongest in those over 65 years at baseline (p for interaction <.001). Discussion and Implications: Depression symptom burden and worsening trajectory predicted delirium risk during hospitalization. Increased awareness of subclinical depression symptoms may aid delirium prevention.

Delineating cognitive resilience using fractal regulation: Cross-sectional and longitudinal evidence from the Rush Memory and Aging Project.

INTRODUCTION: Degradation of fractal patterns in actigraphy independently predicts dementia risk. Such observations motivated the study to understand the role of fractal regulation in the context of neuropathologies. METHODS: We examined associations of fractal regulation with neuropathologies and longitudinal cognitive changes in 533 older participants who were followed annually with actigraphy and cognitive assessments until death with brain autopsy performed. Two measures for fractal patterns were extracted from actigraphy, namely, α1 (representing the fractal regulation at time scales of <90 min) and α2 (for time scales 2 to 10 h). RESULTS: We found that larger α1 was associated with lower burdens of Lewy body disease or cerebrovascular disease pathologies; both α1 and α2 were associated with cognitive decline. They explained an additional significant portion of the variance in the rate of cognitive decline above and beyond neuropathologies. DISCUSSION: Fractal patterns may be used as a biomarker for cognitive resilience against dementia-related neuropathologies.

Medical malpractice litigation and daylight saving time.

STUDY OBJECTIVES: Daylight saving time (DST) constitutes a natural quasi-experiment to examine the influence of mild sleep loss and circadian misalignment. We investigated the acute effects of spring transition into DST and the chronic effects of DST (compared to standard time) on medical malpractice claims in the United States over three decades. METHODS: We analyzed 288,432 malpractice claims from the National Practitioner Data Bank. To investigate the acute effects of spring DST transition, we compared medical malpractice incidents/decisions one week before spring DST transition, one week following spring DST transition, and the rest of the year. To investigate the chronic effects of DST months, we compared medical malpractice incidents/decisions averaged across the 7-8 months of DST versus the 4-5 months of standard time. RESULTS: With regard to acute effects, spring DST transitions were significantly associated with higher payment decisions, but not associated with the severity of medical incidents. With regard to chronic effects, the 7-8 DST months were associated with higher average payments and worse severity of incidents than the 4-5 standard time months. CONCLUSIONS: The mild sleep loss and circadian misalignment associated with DST may influence incidence of medical errors and decisions on medical malpractice payments both acutely and chronically.

Objective and Subjective Intraindividual Variability in Sleep: Predisposing Factors and Health Consequences.

OBJECTIVE: We investigated the factors that predispose or precipitate greater intraindividual variability (IIV) in sleep. We further examined the potential consequences of IIV on overall sleep quality and health outcomes, including whether these relationships were found in both self-reported and actigraphy-measured sleep IIV. METHODS: In Study 1, 699 US adults completed a Sleep Intra-Individual Variability Questionnaire and self-reported psychosocial, sleep quality, and health outcomes. In Study 2, 100 university students wore actigraphy and completed psychosocial, sleep, and health surveys at multiple timepoints. RESULTS: In cross-sectional analyses that controlled for mean sleep duration, predisposing/precipitating factors to greater IIV were being an underrepresented racial/ethnic minority (Study 1: F = 13.95, p < .001; Study 2: F = 7.03, p = .009), having greater stress (Study 2: r values ≥ 0.32, p values ≤ .002) or trait vulnerability to stress (Study 1: r values ≥ 0.15, p values < .001), and showing poorer time management (Study 1: r values ≤ -0.12, p values ≤ .004; Study 2: r values ≤ -0.23, p values ≤ .028). In addition, both studies showed that greater sleep IIV was associated with decreased overall sleep quality, independent of mean sleep duration (Study 1: r values ≥ 0.20, p values < .001; Study 2: r values ≥ 0.33, p values ≤ .001). Concordance across subjective and objective IIV measures was modest ( r values = 0.09-0.35) and similar to concordance observed for subjective-objective mean sleep duration measures. CONCLUSION: Risk for irregular sleep patterns is increased in specific demographic groups and may be precipitated by, or contribute to, higher stress and time management inefficiencies. Irregular sleep may lead to poor sleep quality and adverse health outcomes, independent of mean sleep duration, underscoring the importance of addressing sleep consistency.

Inhibition of PI3K/AKT signaling pathway prevents blood-induced heterotopic ossification of the injured tendon.

Objective: It is a common clinical phenomenon that blood infiltrates into the injured tendon caused by sports injuries, accidental injuries, and surgery. However, the role of blood infiltration into the injured tendon has not been investigated. Methods: A blood-induced rat model was established and the impact of blood infiltration on inflammation and HO of the injured tendon was assessed. Cell adhesion, viability, apoptosis, and gene expression were measured to evaluate the effect of blood treatment on tendon stem/progenitor cells (TSPCs). Then RNA-seq was used to assess transcriptomic changes in tendons in a blood infiltration environment. At last, the small molecule drug PI3K inhibitor LY294002 was used for in vivo and in vitro HO treatment. Results: Blood caused acute inflammation in the short term and more severe HO in the long term. Then we found that blood treatment increased cell apoptosis and decreased cell adhesion and tenonic gene expression of TSPCs. Furthermore, blood treatment promoted osteochondrogenic differentiation of TSPCs. Next, we used RNA-seq to find that the PI3K/AKT signaling pathway was activated in blood-treated tendon tissues. By inhibiting PI3K with a small molecule drug LY294002, the expression of osteochondrogenic genes was markedly downregulated while the expression of tenonic genes was significantly upregulated. At last, we also found that LY294002 treatment significantly reduced the tendon HO in the rat blood-induced model. Conclusion: Our findings indicate that the upregulated PI3K/AKT signaling pathway is implicated in the aggravation of tendon HO. Therefore, inhibitors targeting the PI3K/AKT pathway would be a promising approach to treat blood-induced tendon HO.

Circadian disturbances and frailty risk in older adults.

Frailty is characterized by diminished resilience to stressor events. It is associated with adverse future health outcomes and impedes healthy aging. The circadian system orchestrates ~24-h rhythms in bodily functions in synchrony with the day-night cycle, and disturbed circadian regulation plays an important role in many age-related health consequences. We investigated prospective associations of circadian disturbances with incident frailty in over 1000 older adults who had been followed annually for up to 16 years. We found that decreased rhythm strength, reduced stability, or increased variation were associated with a higher risk of incident frailty and faster progress of frailty over time. Perturbed circadian rest-activity rhythms may be an early sign or risk factor for frailty in older adults.

Associations between depression symptom burden and delirium risk: a prospective cohort study.

BACKGROUND AND OBJECTIVES: Delirium and depression are increasingly common in aging. There is considerable clinical overlap, including shared symptoms and comorbid conditions, including Alzheimer's disease (AD), functional decline, and mortality. Despite this, the long-term relationship between depression and delirium remains unclear. This study assessed the associations of depression symptom burden and its trajectory with delirium risk in a 12-year prospective study of older individuals during hospitalization. RESEARCH DESIGN AND METHODS: 319,141 UK biobank participants between 2006-2010 (mean 58y [range 37-74, SD=8], 54% female) reported frequency (0-3) of four depressive symptoms (mood, disinterest, tenseness, or lethargy) in the preceding 2 weeks, and aggregated into a depressive symptom burden score (0-12). New-onset delirium was obtained from hospitalization records during 12y median follow-up. 40,451 (mean age 57±8; range 40-74y) had repeat assessment on average 8y after their first. Cox proportional hazard models examined whether depression symptom burden and trajectory predicted incident delirium during hospitalization. RESULTS: 5,753 (15 per 1000) newly developed delirium during follow-up. Increased risk for delirium was seen for mild (aggregated scores 1-2, hazards ratio, HR=1.16, [95% confidence interval 1.08-1.25], p<0.001), modest (scores 3-5, 1.30 [1.19-1.43], p<0.001) and severe (scores ≥ 5, 1.38 [1.24-1.55], p<0.001) depressive symptoms, versus none in the fully adjusted model. These findings were independent of the number of hospitalizations and consistent across hospitalization settings (e.g., surgical, medical, or critical care) and specialty (e.g., neuropsychiatric, cardiorespiratory or other). Worsening depression symptoms (≥1 point increase), compared to no change/improved score, were associated with an additional 39% increased risk (1.39 [1.03-1.88], p=0.03) independent of baseline depression burden. The association was strongest in those over 65y at baseline (p for interaction <0.001). DISCUSSION AND IMPLICATIONS: Depression symptom burden and worsening trajectory predicted delirium risk during hospitalization. Increased awareness of subclinical depression symptoms may be warranted for delirium prevention.

Circadian disturbances and frailty risk in older adults: a prospective cohort study.

Frailty is characterized by diminished resilience to stressor events. It associates with adverse future health outcomes and impedes healthy aging. The circadian system orchestrates a ~24-h rhythm in bodily functions in synchrony with the day-night cycle, and disturbed circadian regulation plays an important role in many age-related health consequences. We investigated prospective associations of circadian disturbances with incident frailty in over 1,000 older adults who had been followed annually for up to 16 years. We found that decreased rhythm strength, reduced stability, or increased variation, were associated with a higher risk of incident frailty, and faster worsening of the overall frailty symptoms over time. Perturbed circadian rest-activity rhythms may be an early sign or risk factor for frailty in older adults.

Sleep behavior traits and associations with opioid-related adverse events: a cohort study.

STUDY OBJECTIVES: Opioid-related adverse events (OAEs), including opioid use disorders, overdose, and death, are serious public health concerns. OAEs are often associated with disrupted sleep, but the long-term relationship between poor sleep and subsequent OAE risk remains unknown. This study investigates whether sleep behavior traits are associated with incident OAEs in a large population cohort. METHODS: 444 039 participants (mean age ± SD 57 ± 8 years) from the UK Biobank reported their sleep behavior traits (sleep duration, daytime sleepiness, insomnia-like complaints, napping, and chronotype) between 2006 and 2010. The frequency/severity of these traits determined a poor sleep behavior impacts score (0-9). Incident OAEs were obtained from hospitalization records during 12-year median follow-up. Cox proportional hazards models examined the association between sleep and OAEs. RESULTS: Short and long sleep duration, frequent daytime sleepiness, insomnia symptoms, and napping, but not chronotype, were associated with increased OAE risk in fully adjusted models. Compared to the minimal poor sleep behavior impacts group (scores of 0-1), the moderate (4-5) and significant (6-9) groups had hazard ratios of 1.47 (95% confidence interval [1.27, 1.71]), p < 0.001, and 2.19 ([1.82, 2.64], p < 0.001), respectively. The latter risk magnitude is greater than the risk associated with preexisting psychiatric illness or sedative-hypnotic medication use. In participants with moderate/significant poor sleep impacts (vs. minimal), subgroup analysis revealed that age <65 years was associated with a higher OAE risk than in those ≥65 years. CONCLUSIONS: Certain sleep behavior traits and overall poor sleep impacts are associated with an increased risk for opioid-related adverse events.

Chronotype in college science students is associated with behavioral choices and can fluctuate across a semester.

Many students self-report that they are "night owls," which can result from neurodevelopmental delays in the circadian timing system. However, whether an individual considers themselves to be an evening-type versus a morning-type (self-reported chronotype) may also be influenced by academic demands (e.g. class start times, course load) and behavioral habits (e.g. bedtime social media use, late caffeine consumption, daytime napping). If so, then chronotype should be malleable. We surveyed 858 undergraduate students enrolled in demanding science courses at up to three time points. The survey assessed morning/evening chronotype, global sleep quality, academics, and behavioral habits. Evening and morning-type students showed similar demographics, stress levels, and academic demands. At baseline measurements, relative to morning-types, evening-types showed significantly worse sleep quality and duration as well as 22% greater bedtime social media usage, 27% greater daytime napping duration, and 46% greater likelihood of consuming caffeine after 5pm. These behavioral habits partially mediated the effects of self-reported chronotype on sleep quality/duration, even after controlling for demographic factors. Interestingly, 54 students reported switching from being at least moderate evening-types at baseline to being at least moderate morning-types later in the semester and 56 students showed the reverse pattern (6.3% of students switched from "definitely" one chronotype to the other chronotype). Evening-to-morning "chrono-switchers" consumed less caffeine after 5pm and showed significantly better sleep quantity/quality at the later timepoint. Thus, some students may consider themselves to be night owls in part because they consume caffeine later, take more daytime naps, or use more social media at bedtime. Experimental work is needed to determine whether nudging night owls to behave like morning larks results in better sleep health or academic achievement.

Longitudinal trajectories of spectral power during sleep in middle-aged and older adults.

Age-related changes in sleep appear to contribute to cognitive aging and dementia. However, most of the current understanding of sleep across the lifespan is based on cross-sectional evidence. Using data from the Sleep Heart Health Study, we investigated longitudinal changes in sleep micro-architecture, focusing on whether such age-related changes are experienced uniformly across individuals. Participants were 2,202 adults (ageBaseline = 62.40 ± 10.38, 55.36 % female, 87.92 % White) who completed home polysomnography assessment at two study visits, which were 5.23 years apart (range: 4-7 years). We analyzed NREM and REM spectral power density for each 0.5 Hz frequency bin, including slow oscillation (0.5-1 Hz), delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), sigma (12-15 Hz), and beta-1 (15-20 Hz) bands. Longitudinal comparisons showed a 5-year decline in NREM delta (p <.001) and NREM sigma power density (p <.001) as well as a 5-year increase in theta power density during NREM (p =.001) and power density for all frequency bands during REM sleep (ps < 0.05). In contrast to the notion that sleep declines linearly with advancing age, longitudinal trajectories varied considerably across individuals. Within individuals, the 5-year changes in NREM and REM power density were strongly correlated (slow oscillation: r = 0.46; delta: r = 0.67; theta r = 0.78; alpha r = 0.66; sigma: r = 0.71; beta-1: r = 0.73; ps < 0.001). The convergence in the longitudinal trajectories of NREM and REM activity may reflect age-related neural de-differentiation and/or compensation processes. Future research should investigate the neurocognitive implications of longitudinal changes in sleep micro-architecture and test whether interventions for improving key sleep micro-architecture features (such as NREM delta and sigma activity) also benefit cognition over time.

Circadian Rest-Activity Rhythms, Delirium Risk, and Progression to Dementia.

OBJECTIVE: Delirium is a complex neurocognitive syndrome suspected to be bidirectionally linked to dementia. Circadian rhythm disturbances likely contribute to dementia pathogenesis, but whether these disturbances are related to delirium risk and progression to all-cause dementia is unknown. METHODS: We analyzed continuous actigraphy data from 53,417 middle-aged or older UK Biobank participants during a median 5 years of follow-up. Four measures were used to characterize the 24-hour daily rest-activity rhythms (RARs): normalized amplitude, acrophase representing the peak activity time, interdaily stability, and intradaily variability (IV) for fragmentation of the rhythm. Cox proportional hazards models examined whether RARs predicted incident delirium (n = 551) and progression to dementia (n = 61). RESULTS: Suppressed 24-hour amplitude, lowest (Q1) versus highest (Q4) quartile (hazard ratio [HR]Q1 vs Q4 = 1.94, 95% confidence interval [CI] = 1.53-2.46, p < 0.001), and more fragmented (higher IV: HRQ4 vs Q1 = 1.49, 95% CI = 1.18-1.88, p < 0.001) rhythms predicted higher delirium risk, after adjusting for age, sex, education, cognitive performance, sleep duration/disturbances, and comorbidities. In those free from dementia, each hour of delayed acrophase was associated with delirium risk (HR = 1.13, 95% CI = 1.04-1.23, p = 0.003). Suppressed 24-hour amplitude was associated with increased risk of progression from delirium to new onset dementia (HR = 1.31, 95% CI = 1.03-1.67, p = 0.03 for each 1-standard deviation decrease). INTERPRETATION: Twenty-four-hour daily RAR suppression, fragmentation, and potentially delayed acrophase were associated with delirium risk. Subsequent progression to dementia was more likely in delirium cases with suppressed rhythms. The presence of RAR disturbances before delirium and prior to progression to dementia suggests that these disturbances may predict higher risk and be involved in early disease pathogenesis. ANN NEUROL 2023;93:1145-1157.

COVID-19-Related News Consumption Linked with Stress and Worry, but Not Sleep Quality, Early in the Pandemic.

Beginning in early 2020, the novel coronavirus was the subject of frequent and sustained news coverage. Building on prior literature on the stress-inducing effects of consuming news during a large-scale crisis, we used network analysis to investigate the association between coronavirus disease 2019 (COVID-19) news consumption, COVID-19-related psychological stress, worries about oneself and one's loved ones getting COVID-19, and sleep quality. Data were collected in March 2020 from 586 adults (45.2% female; 72.9% White) recruited via Amazon Mechanical Turk in the U.S. Participants completed online surveys assessing attitudes and behaviors related to COVID-19 and a questionnaire assessing seven domains of sleep quality. Networks were constructed using partial regularized correlation matrices. As hypothesized, COVID-19 news consumption was positively associated with COVID-19-related psychological stress and concerns about one's loved ones getting COVID-19. However, there were very few associations between COVID-19 news consumption and sleep quality indices, and gender did not moderate any of the observed relationships. This study replicates and extends previous findings that COVID-19-news consumption is linked with psychological stress related to the pandemic, but even under such conditions, sleep quality can be spared due to the pandemic allowing for flexibility in morning work/school schedules.

Effect of whole course seamless nursing mode on patients with chronic infectious wounds.

Background: Chronic infectious wounds seriously affect patients' quality of life. Aim: To assess the effect of whole course seamless nursing mode on patients with chronic infectious wounds. Methodology: One hundred patients treated between January 2019 and December 2020 were randomly divided into control and observation groups (n=50) that were given routine nursing and whole course seamless nursing, respectively. Their pain score, comfort score, wound healing time, wound healing effect, psychological state scores, sleep indices, quality-of-life scores and degree of satisfaction with nursing were compared. Results: Observation group had lower pain score and higher comfort score than those of control group after nursing (P<0.05). Compared with control group, observation group had shorter wound healing time and higher grade-A wound healing rate (P<0.05). The SDS and SAS scores of observation group were lower than those of control group (P<0.05). Observation group also had significantly shorter sleep latency, longer actual sleep time, lower PSQI score, as well as higher quality-of-life score and overall satisfaction rate than those of control group (P<0.05). Conclusion: For patients with chronic infectious wounds, whole course seamless nursing effectively relieves wound pain, facilitates wound healing, improves comfort, psychological state and sleep status, and makes them more satisfied.

Actigraphy-Based Sleep Detection: Validation with Polysomnography and Comparison of Performance for Nighttime and Daytime Sleep During Simulated Shift Work.

Purpose: Actigraphy-based sleep detection algorithms were mostly validated using nighttime sleep, and their performance in detecting daytime sleep is unclear. We evaluated and compared the performance of Actiware and the Cole-Kripke algorithm (C-K) - two commonly used actigraphy-based algorithms - in detecting daytime and nighttime sleep. Participants and Methods: Twenty-five healthy young adults were monitored by polysomnography and actigraphy during two in-lab protocols with scheduled nighttime and/or daytime sleep (within-subject design). Mixed-effect models were conducted to compare the sensitivity, specificity, and F1 score (a less-biased measure of accuracy) of Actiware (with low/medium/high threshold setting, separately) and C-K in detecting sleep epochs from actigraphy recordings during nighttime/daytime. t-tests and intraclass correlation coefficients were used to assess the agreement between actigraphy-based algorithms and polysomnography in scoring total sleep time (TST). Results: Sensitivity was similar between nighttime (Actiware: 0.93-0.99 across threshold settings; C-K: 0.61) and daytime sleep (Actiware: 0.93-0.99; C-K: 0.66) for both the C-K and Actiware (daytime/nighttime×algorithm interaction: p > 0.1). Specificity for daytime sleep was lower (Actiware: 0.35-0.54; C-K: 0.91) than that for nighttime sleep (Actiware: 0.37-0.62; C-K: 0.93; p = 0.001). Specificity was also higher for C-K than Actiware (p < 0.001), with no daytime/nighttime×algorithm interaction (p > 0.1). C-K had lower F1 (nighttime = 0.74; daytime = 0.77) than Actiware (nighttime = 0.95-0.98; daytime = 0.90-0.91) for both nighttime and daytime sleep (all p < 0.05). The daytime-nighttime difference in F1 was opposite for Actiware (daytime: 0.90-0.91; nighttime: 0.95-0.98) and C-K (daytime: 0.77; nighttime: 0.74; interaction p = 0.003). Bias in TST was lowest in Actiware (with medium-threshold) for nighttime sleep (underestimation of 5.99 min/8h) and in Actiware (with low-threshold) for daytime sleep (overestimation of 17.75 min/8h). Conclusion: Daytime/nighttime sleep affected specificity and F1 but not sensitivity of actigraphy-based sleep scoring. Overall, Actiware performed better than the C-K algorithm. Actiware with medium-threshold was the least biased in estimating nighttime TST, and Actiware with low-threshold was the least biased in estimating daytime TST.

Daytime Sleep Behaviors and Cognitive Performance in Middle- to Older-Aged Adults Living with and without HIV Infection.

PURPOSE: We investigated whether daytime sleep behaviors (DSBs) such as frequent daytime sleepiness or napping are associated with worse cognitive performance, and whether HIV infection moderates this relationship. METHODS: Among 502,507 participants in the UK Biobank study, we identified 562 people living with HIV infection (PLWH; M age= 50.51±7.81; 25.09% female; 78.83% white) and extracted 562 uninfected controls who matched on age, sex, ethnic background, social-economic status, and comorbidities. DSB burden was assessed based on answers to two questions on DSBs. Participants who answered "sometimes" or "often/usually" to one of them were considered to have poor DSB burden, or otherwise were considered not having any. A composite cognition score was computed by averaging the available standardized individual test results from four neurocognitive tests: ie, a reaction time test for information processing speed, a pairs matching test for visual episodic memory, a fluid intelligence test for reasoning, and a prospective memory test. Mixed-effects models with adjustment for the variables used in extracting matched uninfected controls were performed to test the hypotheses. RESULTS: Having poor DSB burden was associated with a 0.15 - standard deviation (SD) decrease in cognitive performance (p = 0.006). People living with HIV infection (PLWH) also performed worse on the cognitive tasks than uninfected controls, with an effect size similar to that of having poor DSB burden (p = 0.003). HIV infection significantly modified the negative association between DSB burden and cognition (p for interaction: 0.008). Specifically, the association between DSB burden and cognition was not statistically significant in uninfected controls, whereas PLWH who reported having poor DSB burden had a 0.28 - SD decrease in cognitive performance compared to PLWH who did not. CONCLUSION: HIV infection significantly increased the adverse association between DSBs and cognitive performance. Further studies are needed to investigate the potential mechanisms that underlie this interaction effect and whether poor DSBs and worse cognitive performance are causally linked.

Validation of a nonwearable device in healthy adults with normal and short sleep durations.

STUDY OBJECTIVES: To determine the accuracy of early and newer versions of a nonwearable sleep tracking device relative to polysomnography and actigraphy, under conditions of normal and restricted sleep duration. METHODS: Participants were 35 healthy adults (mean age = 18.97; standard deviation = 0.95 years; 77.14% female; 42.86% White). In a controlled sleep laboratory environment, we randomly assigned participants to go to bed at 10:30 pm (normal sleep) or 1:30 am (restricted sleep), setting lights-on at 7:00 am. Sleep was measured using polysomnography, wristband actigraphy (the Philips Respironics Actiwatch Spectrum Plus), self-report, and an early or newer version of a nonwearable device that uses a sensor strip to measure movement, heart rate, and breathing (the Apple, Inc. Beddit). We tested accuracy against polysomnography for total sleep time, sleep efficiency, sleep onset latency, and wake after sleep onset. RESULTS: The early version of the nonwearable device (Beddit 3.0) displayed poor reliability (intraclass correlation coefficient [ICC] < 0.30). However, the newer nonwearable device (Beddit 3.5) yielded excellent reliability with polysomnography for total sleep time (ICC = 0.998) and sleep efficiency (ICC = 0.98) across normal and restricted sleep conditions. Agreement was also excellent for the notoriously difficult metrics of sleep onset latency (ICC = 0.92) and wake after sleep onset (ICC = 0.92). This nonwearable device significantly outperformed clinical-grade actigraphy (ICC between 0.44 and 0.96) and self-reported sleep measures (ICC < 0.75). CONCLUSIONS: A nonwearable device showed better agreement than actigraphy with polysomnography outcome measures. Future work is needed to test the validity of this device in clinical populations. CITATION: Hsiou DA, Gao C, Matlock RC, Scullin MK. Validation of a nonwearable device in healthy adults with normal and short sleep durations. J Clin Sleep Med. 2022;18(3):751-757.

Age moderates the relationships between obesity, glucose variability, and intensive care unit mortality: a retrospective cohort study.

BACKGROUND: Although the associations between obesity, glucose variability (GV), and Intensive Care Unit (ICU) mortality have been studied extensively, whether age moderates these associations is not well understood. MATERIALS AND METHODS: The medical records of 1062 patients, who were admitted into ICU at Sir Run Run Shaw Hospital (Zhejiang, China), were studied. Logistic regression was used to test the associations between obesity, GV, and ICU mortality. Furthermore, the moderation effect of age was tested. RESULTS: After controlling for covariates, the underweight group had the highest odds of death (OR 2.38, 95% CI 1.43-3.95, p < 0.001) in comparison with the control group (overweight). However, normal weight (OR 1.29, 95% CI 0.88-1.89, p = 0.185) and obese (OR 1.08, 95% CI 0.61-1.90, p = 0.790) groups had similar odds of death, compared to the overweight group. Age significantly moderated the association between obesity and mortality, where being overweight was more advantageous than being normal weight in older adults (B = 0.03, SE = 0.01, OR 1.03, 95% CI 1.001-1.06, p = 0.045). Meanwhile, higher GV predicted greater mortality in adjusted models (OR 1.23, 95% CI 1.06-1.42, p = 0.005). We also found an interaction between age and GV (B = - 0.01, SE = 0.01, OR 0.99, 95% CI 0.98-0.999, p = 0.025), which suggested that the association between GV and mortality becomes weaker with increasing age. CONCLUSIONS: With increasing age, the association between BMI and mortality becomes stronger and the association between glucose variability and mortality becomes weaker. Future studies should investigate the underlying mechanisms of such phenomenon and the causal relationship between obesity, GV, and ICU mortality.