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Objective Mindfulness-based interventions (MBI) have been shown to reduce subjective symptoms of insomnia but the effects on objective measures remain unclear. The purpose of this study was to examine sleep EEG microarchitecture patterns from a randomized controlled trial of Mindfulness-Based Stress Reduction (MBSR) and Mindfulness-Based Therapy for Insomnia (MBTI). Methods Sleep EEG spectral analysis was conducted on 36 participants with chronic insomnia (>6 months) randomized to 8-week MBSR, MBTI, or self-monitoring control (SM). Overnight polysomnography with 6-channel EEG was conducted at baseline, post-treatment, and 6-month follow-up. Spectral power averaged from channels C3/C4 across NREM epochs (excluding N1) was examined for within-group changes and relationships with self-report measures. Results Increases in absolute NREM beta (16–25 Hz) power were observed from baseline to post-treatment (p = .02, d = 0.53) and maintained at 6-month follow-up (p = .01, d = 0.57) in the combined MBI groups, and additionally in the gamma (25–40 Hz) range at follow-up for the MBTI group only. No significant changes in these frequency bands were observed for SM. Following mindfulness intervention, NREM beta was positively associated with Five-Facet Mindfulness (FFM) score (rho = 0.37, p = .091) and negatively associated with Insomnia Severity Index (rho = −0.43, p = .047). Conclusion These results in people with insomnia corroborate prior reports of increased high-frequency sleep EEG power associated with mindfulness training. This change in beta EEG pattern merits further evaluation as a potential marker of the effects of mindfulness meditation on sleep, especially given the paradoxical findings in the context of insomnia. Clinical Trial Registration clinicaltrials.gov , NCT00768781 .

Sleep and circadian rhythm changes during adolescence contribute to increased risk across emotional, behavioral, cognitive, social, and physical health domains. This study examines if sleep and dim light melatonin onset (DLMO) are related to greater risk in these 5 health domains. Participants were 163 (93 female, age = 14.7 years) adolescents with an evening circadian preference from a study funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Sleep and circadian measures included weekday total sleep time (TST), bedtime, and shut-eye time assessed via sleep diary, the Children's Morningness-Eveningness Preferences scale, and DLMO. Health domains included self-reported emotional, cognitive, behavioral, social, and physical health. Later DLMO was significantly associated with shorter weekday TST, later weekday bedtime, and later weekday shut-eye time, as well as lower risk in the behavioral domain. At the trend level, later DLMO was related to fewer physical health problems. Earlier DLMO combined with a later bedtime, later shut-eye time, or shorter TST predicted greater risk in the cognitive domain. Later DLMO and shorter TST or a later bedtime predicted worse physical health. DLMO timing was not related to the emotional or social domain. There is evidence that a discrepancy between sleep behaviors and the endogenous circadian rhythm may be related to risk in the cognitive domain for adolescents with an evening circadian preference. Preliminary evidence also indicated that a delayed DLMO and shorter TST or a later bedtime may be related to vulnerability to physical health risk.

Objective/Background To compare sleep and circadian variability in adults with delayed sleep–wake phase disorder (DSWPD) to healthy controls. Patients/Methods Forty participants (22 DSWPD, 18 healthy controls) completed a ten-day protocol, consisting of DLMO assessments on two consecutive nights, a five-day study break, followed by two more DLMO assessments. All participants were instructed to sleep within one hour of their self-reported average sleep schedule for the last four days of the study break. We analyzed the participants' wrist actigraphy data during these four days to examine intraindividual variability in sleep timing, duration and efficiency. We also examined shifts in the DLMO from before and after the study break. Results and conclusions Under the same conditions, people with DSWPD had significantly more variable wake times and total sleep time than healthy controls (p ≤ 0.015). Intraindividual variability in sleep onset time and sleep efficiency was similar between the two groups (p ≥ 0.30). The DLMO was relatively stable across the study break, with only 11% of controls but 27% of DSWPDs showed more than a one hour shift in the DLMO. Only in the DSWPD sample was greater sleep variability associated with a larger shift in the DLMO (r = 0.46, p = 0.03). These results suggest that intraindividual variability in sleep can be higher in DSWPD versus healthy controls, and this may impact variability in the DLMO. DSWPD patients with higher intraindividual variability in sleep are more likely to have a shifting DLMO, which could impact sleep symptoms and the optimal timing of light and/or melatonin treatment for DSWPD. Clinical trial Circadian Phase Assessments at Home, http://clinicaltrials.gov/show/NCT01487252 , NCT01487252 .

Objective To determine whether an intervention to reduce eveningness chronotype improves sleep, circadian, and health (emotional, cognitive, behavioral, social, physical) outcomes. Method Youth aged 10 to 18 years with an evening chronotype and who were “at risk” in 1 of 5 health domains were randomized to: (a) Transdiagnostic Sleep and Circadian Intervention for Youth (TranS-C; n = 89) or (b) Psychoeducation (PE; n = 87) at a university-based clinic. Treatments were 6 individual, weekly 50-minute sessions during the school year. TranS-C addresses sleep and circadian problems experienced by youth by integrating evidence-based treatments derived from basic research. PE provides education on the interrelationship between sleep, stress, diet, and health. Results Relative to PE, TranS-C was not associated with greater pre−post change for total sleep time (TST) or bed time (BT) on weeknights but was associated with greater reduction in evening circadian preference (pre−post increase of 3.89 points, 95% CI = 2.94−4.85, for TranS-C, and 2.01 points, 95% CI = 1.05−2.97 for PE, p = 0.006), earlier endogenous circadian phase, less weeknight−weekend discrepancy in TST and wakeup time, less daytime sleepiness, and better self-reported sleep via youth and parent report. In terms of functioning in the five health domains, relative to PE, TranS-C was not associated with greater pre−post change on the primary outcome. However, there were significant interactions favoring TranS-C on the Parent-Reported Composite Risk Scores for cognitive health. Conclusion For at-risk youth, the evidence supports the use of TranS-C over PE for improving sleep and circadian functioning, and improving health on selected outcomes. Clinical trial registration information: Triple Vulnerability? Circadian Tendency, Sleep Deprivation and Adolescence. https://clinicaltrials.gov ; NCT01828320 .

Study Objectives: This study examined empirically derived symptom cluster profiles among patients who present with insomnia using clinical data and polysomnography. Methods: Latent profile analysis was used to identify symptom cluster profiles of 175 individuals (63% female) with insomnia disorder based on total scores on validated self-report instruments of daytime and nighttime symptoms (Insomnia Severity Index, Glasgow Sleep Effort Scale, Fatigue Severity Scale, Beliefs and Attitudes about Sleep, Epworth Sleepiness Scale, Pre-Sleep Arousal Scale), mean values from a 7-day sleep diary (sleep onset latency, wake after sleep onset, and sleep efficiency), and total sleep time derived from an in-laboratory PSG. Results: The best-fitting model had three symptom cluster profiles: "High Subjective Wakefulness" (HSW), "Mild Insomnia" (MI) and "Insomnia-Related Distress" (IRD). The HSW symptom cluster profile (26.3% of the sample) reported high wake after sleep onset, high sleep onset latency, and low sleep efficiency. Despite relatively comparable PSG-derived total sleep time, they reported greater levels of daytime sleepiness. The MI symptom cluster profile (45.1%) reported the least disturbance in the sleep diary and questionnaires and had the highest sleep efficiency. The IRD symptom cluster profile (28.6%) reported the highest mean scores on the insomnia-related distress measures (eg, sleep effort and arousal) and waking correlates (fatigue). Covariates associated with symptom cluster membership were older age for the HSW profile, greater obstructive sleep apnea severity for the MI profile, and, when adjusting for obstructive sleep apnea severity, being overweight/obese for the IRD profile. Conclusions: The heterogeneous nature of insomnia disorder is captured by this data-driven approach to identify symptom cluster profiles. The adaptation of a symptom cluster-based approach could guide tailored patient-centered management of patients presenting with insomnia, and enhance patient care.

The purpose of this study was to introduce a novel statistical technique called the location-scale mixed model that can be used to analyze the mean level and intra-individual variability (IIV) using longitudinal sleep data.We applied the location-scale mixed model to examine changes from baseline in sleep efficiency on data collected from 54 participants with chronic insomnia who were randomized to an 8-week Mindfulness-Based Stress Reduction (MBSR; n = 19), an 8-week Mindfulness-Based Therapy for Insomnia (MBTI; n = 19), or an 8-week self-monitoring control (SM; n = 16). Sleep efficiency was derived from daily sleep diaries collected at baseline (days 1-7), early treatment (days 8-21), late treatment (days 22-63), and post week (days 64-70). The behavioral components (sleep restriction, stimulus control) were delivered during late treatment in MBTI.For MBSR and MBTI, the pre-to-post change in mean levels of sleep efficiency were significantly larger than the change in mean levels for the SM control, but the change in IIV was not significantly different. During early and late treatment, MBSR showed a larger increase in mean levels of sleep efficiency and a larger decrease in IIV relative to the SM control. At late treatment, MBTI had a larger increase in the mean level of sleep efficiency compared to SM, but the IIV was not significantly different.The location-scale mixed model provides a two-dimensional analysis on the mean and IIV using longitudinal sleep diary data with the potential to reveal insights into treatment mechanisms and outcomes.

Background: we previously demonstrated that patients with mild Alzheimer’s disease and parkinsonian features (AD + PF) are at a higher risk of having daytime sleepiness than mild AD patients without PF (AD −PF). Objective: to determine whether AD + PF patients demonstrate a known a consequence of daytime sleepiness, reduced performance-based sustained attention, compared with AD −PF patients. Methods: a nocturnal polysomnogram and a next-day multiple sleep latency test (MSLT) were performed. Between MSLT nap opportunities, a 10-min psychomotor vigilance test (PVT) was administered and analysed for reciprocal mean response times (IMEAN), number of lapses (LAPSE) and reciprocal mean slowest 10% (ISLOW). Results: a total of 35 patients met criteria (AD + PF, n= 16; AD −PF, n= 19). Comparatively, the AD + PF group had slower IMEAN results [F(1,28) = 6.64, P< 0.05] and higher LAPSE rates [F(1,27)= 7.57, P< 0.05]. ISLOW measures were not different between groups. When accounting for MSLT results, IMEAN and LAPSE results were no longer significantly different between groups during morning tests, but remained significantly different on afternoon tests. Conclusion: PFs in mild AD are associated with decreased sustained attention as measured by the PVT. Sleepiness did not fully account for the impairment in sustained attention, suggesting that the presence of PFs has an independent negative association with sustained attention in mild AD.

The purpose of this study was to examine the process of care in an interdisciplinary sleep clinic for patients with obstructive sleep apnea (OSA) and comorbid insomnia. A mixed-methods approach was used to examine clinical and patient-centered measures for 34 patients who received positive-airway pressure for OSA or cognitive-behavior therapy for insomnia. The results revealed baseline-to-follow-up improvements on several self-reported sleep parameters and measures of daytime functioning. Qualitative analyses from patient interviews revealed three themes: conceptual distinctions about each sleep disorder, importance of treating both sleep disorders, and preferences with regard to the sequence of treatment. These findings indicate that patients with OSA and comorbid insomnia encounter unique challenges. A dimensional approach to assessment and treatment is proposed for future research.

Study objectives There is a need for the accurate assessment of circadian phase outside of the clinic/laboratory, particularly with the gold standard dim light melatonin onset (DLMO). We tested a novel kit designed to assist in saliva sampling at home for later determination of the DLMO. The home kit includes objective measures of compliance to the requirements for dim light and half-hourly saliva sampling. Design Participants were randomized to one of two 10-day protocols. Each protocol consisted of two back-to-back home and laboratory phase assessments in counterbalanced order, separated by a 5-day break. Setting Laboratory or participants' homes. Participants Thirty-five healthy adults, age 21-62 y. Interventions N/A. Measurements and results Most participants received at least one 30-sec epoch of light > 50 lux during the home phase assessments (average light intensity 4.5 lux), but on average for 50 lux or sampling errors. There was no significant difference between the home and laboratory DLMOs (P > 0.05); on average the home DLMOs occurred 9.6 min before the laboratory DLMOs. The home DLMOs were highly correlated with the laboratory DLMOs (r = 0.91, P Conclusions Participants were reasonably compliant to the home phase assessment procedures. The good agreement between the home and laboratory dim light melatonin onsets (DLMOs) demonstrates that including objective measures of light exposure and sample timing during home saliva sampling can lead to accurate home DLMOs. Clinical trial registration Circadian Phase Assessments at Home, http://clinicaltrials.gov/show/NCT01487252, NCT01487252.

Study objectives To investigate the effects of a physiologic and a pharmacologic dose of exogenous melatonin on sleep latency and sleep efficiency in sleep episodes initiated across a full range of circadian phases. Design Double-blind placebo-controlled parallel-group design in a 27-day forced desynchrony paradigm with a 20-hour scheduled sleep-wake cycle. Setting Private suite of a general clinical research center, in the absence of time-of-day information. Subjects Thirty-six healthy, 18- to 30-year-old, men (n = 21) and women (n = 15). Interventions Oral melatonin (0.3 mg or 5.0 mg) or identical-appearing placebo was administered 30 minutes prior to each 6.67-hour sleep episode during forced desynchrony. Measurements and results Both doses of melatonin improved polysomnographically determined sleep efficiency from 77% in the placebo group to 83% for sleep episodes occurring during circadian phases when endogenous melatonin was absent. However, this remained below the average sleep efficiency of 88% observed during sleep episodes scheduled during the circadian night, when endogenous melatonin was present. Melatonin did not significantly affect sleep initiation or core body temperature. Melatonin appeared to maintain efficacy across the study and did not significantly affect percentages of slow-wave sleep or rapid eye movement sleep. Conclusions Exogenous melatonin administration possesses circadian-phase-dependent hypnotic properties, allowing for improved consolidation of sleep that occurs out of phase with endogenous melatonin secretion during the circadian night. The results support the hypothesis that both exogenous and endogenous melatonin attenuate the wake-promoting drive from the circadian system.

The separate contribution of circadian rhythmicity and elapsed time awake on electroencephalographic (EEG) activity during wakefulness was assessed. Seven men lived in an environmental scheduling facility for 4 weeks and completed fourteen 42.85-h 'days', each consisting of an extended (28.57-h) wake episode and a 14.28-h sleep opportunity. The circadian rhythm of plasma melatonin desynchronized from the 42.85-h day. This allowed quantification of the separate contribution of circadian phase and elapsed time awake to variation in EEG power spectra (1-32 Hz). EEG activity during standardized behavioral conditions was markedly affected by both circadian phase and elapsed time awake in an EEG frequency- and derivation-specific manner. The nadir of the circadian rhythm in alpha (8-12 Hz) activity in both fronto-central and occipito-parietal derivations occurred during the biological night, close to the crest of the melatonin rhythm. The nadir of the circadian rhythm of theta (4.5-8 Hz) and beta (20-32 Hz) activity in the fronto-central derivation was located close to the onset of melatonin secretion, i.e. during the wake maintenance zone. As time awake progressed, delta frequency (1-4.5 Hz) and beta (20-32 Hz) activity rose monotonically in frontal derivations. The interaction between the circadian and wake-dependent increase in frontal delta was such that the intrusion of delta was minimal when sustained wakefulness coincided with the biological day, but pronounced during the biological night. Our data imply that the circadian pacemaker facilitates frontal EEG activation during the wake maintenance zone, by generating an arousal signal that prevents the intrusion of low-frequency EEG components, the propensity for which increases progressively during wakefulness.

STUDY OBJECTIVES To evaluate the efficacy of mindfulness meditation for the treatment of chronic insomnia. DESIGN Three-arm, single-site, randomized controlled trial. SETTING Academic medical center. PARTICIPANTS Fifty-four adults with chronic insomnia. INTERVENTIONS Participants were randomized to either mindfulness-based stress reduction (MBSR), mindfulness-based therapy for insomnia (MBTI), or an eight-week self-monitoring (SM) condition. MEASUREMENTS AND RESULTS Patient-reported outcome measures were total wake time (TWT) from sleep diaries, the pre-sleep arousal scale (PSAS), measuring a prominent waking correlate of insomnia, and the Insomnia Severity Index (ISI) to determine remission and response as clinical endpoints. Objective sleep measures were derived from laboratory polysomnography and wrist actigraphy. Linear mixed models showed that those receiving a meditation-based intervention (MBSR or MBTI) had significantly greater reductions on TWT minutes (43.75 vs 1.09), PSAS (7.13 vs 0.16), and ISI (4.56 vs 0.06) from baseline-to-post compared to SM. Post hoc analyses revealed that each intervention was superior to SM on each of the patient-reported measures, but no significant differences were found when comparing MBSR to MBTI from baseline-to-post. From baseline to 6-month follow-up, MBTI had greater reductions in ISI scores than MBSR (P < 0.05), with the largest difference occurring at the 3-month follow-up. Remission and response rates in MBTI and MBSR were sustained from post-treatment through follow-up, with MBTI showing the highest rates of treatment remission (50%) and response (78.6%) at the 6-month follow-up. CONCLUSIONS Mindfulness meditation appears to be a viable treatment option for adults with chronic insomnia and could provide an alternative to traditional treatments for insomnia. TRIAL REGISTRATION Mindfulness-Based Approaches to Insomnia: clinicaltrials.gov, identifier: NCT00768781.

Sleep, circadian rhythm, and neurobehavioral performance measures were obtained in five astronauts before, during, and after 16-day or 10-day space missions. In space, scheduled rest-activity cycles were 20–35 min shorter than 24 h. Light-dark cycles were highly variable on the flight deck, and daytime illuminances in other compartments of the spacecraft were very low (5.0–79.4 lx). In space, the amplitude of the body temperature rhythm was reduced and the circadian rhythm of urinary cortisol appeared misaligned relative to the imposed non-24-h sleep-wake schedule. Neurobehavioral performance decrements were observed. Sleep duration, assessed by questionnaires and actigraphy, was only ∼6.5 h/day. Subjective sleep quality diminished. Polysomnography revealed more wakefulness and less slow-wave sleep during the final third of sleep episodes. Administration of melatonin (0.3 mg) on alternate nights did not improve sleep. After return to earth, rapid eye movement (REM) sleep was markedly increased. Crewmembers on these flights experienced circadian rhythm disturbances, sleep loss, decrements in neurobehavioral performance, and postflight changes in REM sleep.

To understand the factors that alter sleep quality in space, we studied the effect of spaceflight on sleep-disordered breathing. We analyzed 77 8-h, full polysomnographic recordings (PSGs) from five healthy subjects before spaceflight, on four occasions per subject during either a 16- or 9-d space shuttle mission and shortly after return to earth. Microgravity was associated with a 55% reduction in the apnea-hypopnea index (AHI), which decreased from a preflight value of 8.3 +/- 1.6 to 3.4 +/- 0.8 events/h inflight. This reduction in AHI was accompanied by a virtual elimination of snoring, which fell from 16.5 +/- 3.0% of total sleep time preflight to 0.7 +/- 0.5% inflight. Electroencephalogram (EEG) arousals also decreased in microgravity (by 19%), and this decrease was almost entirely a consequence of the reduction in respiratory-related arousals, which fell from 5.5 +/- 1.2 arousals/h preflight to 1.8 +/- 0.6 inflight. Postflight there was a return to near or slightly above preflight levels in these variables. We conclude that sleep quality during spaceflight is not degraded by sleep-disordered breathing. This is the first direct demonstration that gravity plays a dominant role in the generation of apneas, hypopneas, and snoring in healthy subjects.

The interaction of homeostatic and circadian processes in the regulation of waking neurobehavioral functions and sleep was studied in six healthy young subjects. Subjects were scheduled to 15–24 repetitions of a 20-h rest/activity cycle, resulting in desynchrony between the sleep-wake cycle and the circadian rhythms of body temperature and melatonin. The circadian components of cognitive throughput, short-term memory, alertness, psychomotor vigilance, and sleep disruption were at peak levels near the temperature maximum, shortly before melatonin secretion onset. These measures exhibited their circadian nadir at or shortly after the temperature minimum, which in turn was shortly after the melatonin maximum. Neurobehavioral measures showed impairment toward the end of the 13-h 20-min scheduled wake episodes. This wake-dependent deterioration of neurobehavioral functions can be offset by the circadian drive for wakefulness, which peaks in the latter half of the habitual waking day during entrainment. The data demonstrate the exquisite sensitivity of many neurobehavioral functions to circadian phase and the accumulation of homeostatic drive for sleep.

Previous research has suggested an association between the subjective report of illness from environmental chemical odors and poorer cognitive task performance in persons with industrial levels of xenobiotic exposures. The present study investigated baseline morning performance on a computerized divided attention task in active retired adults without occupational exposures or clinical disorders who nonetheless rated themselves currently high versus low in episodic illness from the odor of certain environmental chemicals. The chemically intolerant group showed slower reaction times in registering both centrally and peripherally placed stimuli, but no difference in making target tracking errors. Measures of negative affect did not account for these findings. Taken together with evidence for heightened neurobehavioral sensitization in this population, the data suggest disturbances in allocation of attention and related cognitive functions.

Sleep restriction causes impaired cognitive performance that can result in adverse consequences in many occupational settings. Individuals may rely on self-perceived alertness to decide if they are able to adequately perform a task. It is therefore important to determine the relationship between an individual's self-assessed alertness and their objective performance, and how this relationship depends on circadian phase, hours since awakening, and cumulative lost hours of sleep. Healthy young adults (aged 18-34) completed an inpatient schedule that included forced desynchrony of sleep/wake and circadian rhythms with twelve 42.85-hour "days" and either a 1:2 (n = 8) or 1:3.3 (n = 9) ratio of sleep-opportunity:enforced-wakefulness. We investigated whether subjective alertness (visual analog scale), circadian phase (melatonin), hours since awakening, and cumulative sleep loss could predict objective performance on the Psychomotor Vigilance Task (PVT), an Addition/Calculation Test (ADD) and the Digit Symbol Substitution Test (DSST). Mathematical models that allowed nonlinear interactions between explanatory variables were evaluated using the Akaike Information Criterion (AIC). Subjective alertness was the single best predictor of PVT, ADD, and DSST performance. Subjective alertness alone, however, was not an accurate predictor of PVT performance. The best AIC scores for PVT and DSST were achieved when all explanatory variables were included in the model. The best AIC score for ADD was achieved with circadian phase and subjective alertness variables. We conclude that subjective alertness alone is a weak predictor of objective vigilant or cognitive performance. Predictions can, however, be improved by knowing an individual's circadian phase, current wake duration, and cumulative sleep loss.

The purpose of the present study was to examine explicit and implicit memory for auditory events presented immediately prior to sleep onset. The results of the present study suggest subjects allowed 10 minutes of sleep demonstrate deficient explicit memory for auditory stimuli presented immediately prior to sleep onset. Subjects showed severe free recall deficits for word pairs presented 3 minutes prior to sleep onset and recognition deficits for stimuli from 1 minute prior to sleep onset. Implicit memory for word pairs presented prior to sleep onset seemed intact, and no recency effect was observed. In contrast to the 10-minute condition, subjects allowed 30 seconds of sleep demonstrated no equivalent explicit memory deficits. Memory performance in both delay conditions, however, appeared globally impaired relative to control data from subjects who remained awake. The results are interpreted in terms of elaboration of stimulus encoding, interruption of consolidation and retrograde versus anterograde amnesia.

The circadian rhythms of melatonin and body temperature are set to an earlier hour in women than in men, even when the women and men maintain nearly identical and consistent bedtimes and wake times. Moreover, women tend to wake up earlier than men and exhibit a greater preference for morning activities than men. Although the neurobiological mechanism underlying this sex difference in circadian alignment is unknown, multiple studies in nonhuman animals have demonstrated a sex difference in circadian period that could account for such a difference in circadian alignment between women and men. Whether a sex difference in intrinsic circadian period in humans underlies the difference in circadian alignment between men and women is unknown. We analyzed precise estimates of intrinsic circadian period collected from 157 individuals (52 women, 105 men; aged 18–74 y) studied in a month-long inpatient protocol designed to minimize confounding influences on circadian period estimation. Overall, the average intrinsic period of the melatonin and temperature rhythms in this population was very close to 24 h [24.15 ± 0.2 h (24 h 9 min ± 12 min)]. We further found that the intrinsic circadian period was significantly shorter in women [24.09 ± 0.2 h (24 h 5 min ± 12 min)] than in men [24.19 ± 0.2 h (24 h 11 min ± 12 min); P < 0.01] and that a significantly greater proportion of women have intrinsic circadian periods shorter than 24.0 h (35% vs. 14%; P < 0.01). The shorter average intrinsic circadian period observed in women may have implications for understanding sex differences in habitual sleep duration and insomnia prevalence.

Study objectives We explored differences between individuals with DSM-IV-TR diagnoses of primary insomnia (PI) and insomnia related to a mental disorder (IMD) by using serial measurements of self-reported sleep variables (sleep onset latency, SOL; wake after sleep onset, WASO; total sleep time, TST; sleep efficiency, SE), and visual analogue scale ratings of 2 forms of bedtime arousal (cognitive and emotional). Furthermore, we sought to examine the relationship between sleep and arousal within each diagnostic subgroup. Design Between-group and within-group comparisons. Setting Duke and Rush University Medical Centers, USA. Participants One hundred eighty-seven insomnia sufferers (126 women, average age 47.15 years) diagnosed by sleep specialists at 2 sleep centers as PI patients (n=126) and IMD patients (n=61). Interventions N/A. Measurements and results Multilevel models for sleep measures indicated that IMD displayed significantly more instability across nights in their TST (i.e., larger changes) than did PI patients. With respect to pre-sleep arousal, IMD patients exhibited higher mean levels of emotional arousal, as well as more instability on the nightly ratings of this measure. Within the PI group, correlational analyses revealed a moderate relationship between the 2 arousal variables and SOL (r values 0.29 and 0.26), whereas the corresponding correlations were negligible and statistically nonsignificant in the IMD group. Conclusions We found a number of differences on nighttime variables between those diagnosed with primary insomnia and those diagnosed with insomnia related to a mental disorder. These differences imply different perpetuating mechanisms involved in their ongoing sleep difficulties. Additionally, they support the categorical distinctiveness and the concurrent validity of these insomnia subtypes.

BACKGROUND: Excessive daytime sleepiness (EDS) and nocturnal sleep disruption are common in Alzheimer's disease (AD). However, little is known regarding risk factors for developing EDS and sleep disruption in AD. In AD, EDS is associated with Parkinsonian motor features (PF), which are associated with faster cognitive decline. The primary aim of this exploratory study was to evaluate whether differences in EDS and nocturnal sleep disruption exist between AD participants with versus without PF. METHODS: Thirty-six participants with mild AD were evaluated for PF using the modified motor UPDRS (mmUPDRS) scoring system and classified according to absence (AD-PF, n=19) or presence (AD+PF, n=17) of PF. EDS was assessed using questionnaires and a multiple sleep latency test (MSLT) performed the day after nocturnal polysomnogram. Participants were considered "Sleepy" or "Not Sleepy" according to mean MSLT scores (cutoff score=10.4min). RESULTS: Results showed that the AD+PF group were sleepier than the AD-PF group by subjective and objective measures, despite similarities in nocturnal sleep. The AD+PF group had higher scores on the Epworth Sleepiness Scale (8.5 versus 3.9, p=.001). The AD+PF group also had higher percentage of participants that had "Sleepy" MSLT scores compared to the AD-PF group (75% versus 31.6%, respectively; χ(2)=6.56, p=.01). CONCLUSIONS: The presence of Parkinsonian features may be an independent risk factor for sleepiness in mild AD. Language: en

ACROSS A TYPICAL WAKING DAY, PERFORMANCE AND ALERTNESS ARE QUITE STABLE IN WELL-RESTED ADULTS.1 NEUROBEHAVIORAL PERFORMANCE has been shown to be influenced by both sleep-wake homeostatic (duration of prior wakefulness) and circadian (phase of the endogenous biological clock) influences. Achievement of stable performance and alertness across a normal ∼16-h waking day is hypothesized to result from the wake-dependent decline in alertness and performance being counterbalanced by an increasing wake-promoting signal from the circadian timing system that peaks towards the latter part of the habitual wake episode.2 Previous studies using designs that disrupt, restrict, and/or deprive subjects of sleep have all reported that subjective sleepiness and performance, including cognitive throughput, sustained vigilance, visual search tasks, and memory tasks, worsen with longer durations of time awake.1,3–5 Data from constant routine protocols in which subjects remain awake but in constant environmental and behavioral conditions have also shown that as time awake increases, performance decreases. These findings have been reported across a range of wake durations,1 including extreme conditions of up to 88 h of sleep deprivation.6 However, even under conditions of extreme sleep deprivation, progressive impairments in performance are reduced during the biological day compared to the biological night,1,6 an indication of the influence of the circadian timing system. This influence is such that for most measures, performance is best during the biological daytime and worst in the late biological nighttime, at or just after the circadian phase of the core body temperature nadir.1,6 The limitation of sleep deprivation protocols is that there is a confound between duration of prior wakefulness and circadian phase, and hence the independent contributions of each of these sleep-wake regulatory factors on performance cannot be estimated. The forced desynchrony protocol is a paradigm through which wake-dependent and circadian influences on performance in humans can be separated and quantified, and their interaction can be assessed. This protocol involves scheduling the subject to a rest-activity cycle duration much shorter or much longer than 24 h, beyond the range of entrainment of the circadian pacemaker.7 Using the forced desynchrony paradigm, we have reported previously that, in young adults, subjective alertness and neurobehavioral performance are affected by the duration of sustained wakefulness (a wake-dependent homeostatic process) as well as by a circadian process, and that these two processes interact such that the circadian influence on alertness and performance is stronger with greater durations of prior wakefulness.1,4,8 Similar results were achieved using imposed day lengths shorter (20 h, with 13.3 h wake),4 longer (28 h, with 18.7 h wake),1 and significantly longer than normal (42.85 h with 28.57 h wake).8 How these wake-dependent and circadian influences on performance may change with age has not been studied systematically. There are suggestions from sleep fragmentation and sleep deprivation studies that there may be age-related changes in both of these systems. An assessment of the effect of sleep fragmentation on performance in young and older subjects, in which subjects were aroused periodically throughout the sleep episode, found the performance of older subjects to be less sensitive to sleep disturbance than younger subjects,9 suggesting an age-related attenuation of the wake-dependent homeostatic influence on performance. Assessment of the response of young and older subjects to varying durations of sleep deprivation has also been performed. In a study conducted in our laboratory, we found that older adults were better able than young adults to maintain alertness and sustained attention across 26 h.10 Similar results were obtained from a study of 40 h of sleep deprivation in young and older subjects, in which the authors reported that older subjects were able to maintain virtually stable reaction time performance while younger subjects showed greater performance impairments.11 In addition to sleep fragmentation and sleep deprivation studies, results from sleep restriction studies have also suggested that older adults are less susceptible to circadian and wake-dependent performance decrements.12,13 While there is evidence from those prior studies that there may be modifications in both the circadian and wake-dependent homeostatic influences on performance with aging, the designs used in those studies did not allow for the separation of circadian and homeostatic influences, and therefore in most cases, circadian and wake-dependent influences were confounded. Therefore, one purpose of our present analysis was to separate the wake-dependent and circadian influences on performance in older adults to quantify their relative influences, and to compare those findings with results from young adults. In addition, most prior reports on performance in young adults from forced desynchrony studies averaged data across the entire forced desynchrony segment (typically 3-4 weeks), leaving open the possibility that the circadian and/or wake-dependent influence on performance might change across such a long experiment. A second purpose of the present analysis was therefore to examine subjective alertness and performance with respect to how long subjects were exposed to the repeated circadian phase misalignment inherent in forced desynchrony, and to determine whether this differed between young and older subjects. We selected subjective alertness and performance data from older subjects who participated in a 20-h forced desynchrony study and compared them with data previously-reported from young subjects in a 20-h forced desynchrony study.4

Objective To investigate whether the effectiveness of a novel high-frequency low-dose caffeine regimen in counteracting the deterioration of performance during extended wakefulness is related to its interaction with homeostatic or circadian signals modulating performance and sleep propensity. Design Double-blind, placebo-controlled, parallel-group design in a 29-day forced desynchrony paradigm in which the period of the sleep-wake cycle was scheduled to be 42.85 hours, i.e., far removed from the circadian range. This design allowed for separate estimation of the sleep homeostatic, circadian, and caffeine contributions to performance deficits or improvements. Setting Private suite of a general clinical research center, in the absence of time of day information. Participants Sixteen healthy normal-sleeping men (aged 18-30 years) Interventions Caffeine (0.3 mg per kg per hour) or placebo was administered hourly during the 28.57-hour wake episodes. Results Plasma caffeine concentrations rose in an exponential saturating manner during wakefulness. Rising caffeine levels markedly attenuated wake-dependent deterioration of a number of measures of cognitive performance, particularly at the circadian performance nadir. Moreover, caffeine enhanced the ability of subjects to remain consistently awake for extended periods, holding subjects back from completing the full transition to sleep, but at the expense of increasing subjective sleepiness. Conclusions High-frequency low-dose caffeine administration is effective in countering the detrimental performance effects of extended wakefulness. These data are in accordance with the hypothesis that adenosine is a mediator of performance decrements associated with extended wakefulness and may lead to new strategies to use caffeine in situations in which neurobehavioral functioning is affected by sleep loss.

The aim of this study was to quantify the associations between slow eye movements (SEMs), eye blink rate, waking electroencephalogram (EEG) power density, neurobehavioral performance, and the circadian rhythm of plasma melatonin in a cohort of 10 healthy men during up to 32 h of sustained wakefulness. The time course of neurobehavioral performance was characterized by fairly stable levels throughout the first 16 h of wakefulness followed by deterioration during the phase of melatonin secretion. This deterioration was closely associated with an increase in SEMs. Frontal low-frequency EEG activity (1–7 Hz) exhibited a prominent increase with time awake and little circadian modulation. EEG alpha activity exhibited circadian modulation. The dynamics of SEMs and EEG activity were phase locked to changes in neurobehavioral performance and lagged the plasma melatonin rhythm. The data indicate that frontal areas of the brain are more susceptible to sleep loss than occipital areas. Frontal EEG activity and ocular parameters may be used to monitor and predict changes in neurobehavioral performance associated with sleep loss and circadian misalignment.

Alertness and performance on a wide variety of tasks are impaired immediately upon waking from sleep due to sleep inertia, which has been found to dissipate in an asymptotic manner following waketime. It has been suggested that behavioural or environmental factors, as well as sleep stage at awakening, may affect the severity of sleep inertia. In order to determine the time course of sleep inertia dissipation under normal entrained conditions, subjective alertness and cognitive throughput were measured during the first 4 h after habitual waketime from a full 8-h sleep episode on 3 consecutive days. We investigated whether this time course was affected by either sleep stage at awakening or behavioural/environmental factors. Sleep inertia dissipated in an asymptotic manner and took 2-4 h to near the asymptote. Saturating exponential functions fitted the sleep inertia data well, with time constants of 0.67 h for subjective alertness and 1.17 h for cognitive performance. Most awakenings occurred out of stage rapid eye movement (REM), 2 or 1 sleep, and no effect of sleep stage at awakening on either the severity of sleep inertia or the time course of its dissipation could be detected. Subjective alertness and cognitive throughput were significantly impaired upon awakening regardless of whether subjects got out of bed, ate breakfast, showered and were exposed to ordinary indoor room light (approximately 150 lux) or whether subjects participated in a constant routine (CR) protocol in which they remained in bed, ate small hourly snacks and were exposed to very dim light (10-15 lux). These findings allow for the refinement of models of alertness and performance, and have important implications for the scheduling of work immediately upon awakening in many occupational settings.

In this study, we tested the hypothesis that low-level chemical odor intolerance (i.e., "cacosmia") is a manifestation of heightened sensitizability to environmental stimuli. We examined supine heart rate and blood pressure of elderly individuals, who were classified as either having a higher degree of chemical odor intolerance (n = 12) or a lower degree of chemical odor intolerance (n = 13), upon awakening in a sleep research laboratory on 6 different days during an 8-wk protocol. During the 2 initial wk, they consumed a customary baseline diet (including ad lib milk and other dairy products), followed by 3 wk each of nondairy-containing and dairy-containing diets in randomly assigned, counterbalanced order. Measurements were made on 3 pairs of successive days, distributed over a 6-wk period, and on which different diets were consumed. The high-intolerance group had significantly higher mean supine systolic and diastolic blood pressures than did the low-intolerance group. Although subjects consumed milk products during both the initial baseline and subsequent dairy diet periods, the high-intolerance group had significantly higher heart rates and diastolic blood pressures later in the study than at baseline, especially when they were on the dairy diet. In contrast, the cardiovascular measures of the low-intolerance group lowered on average with time. The high-intolerance subjects had an increased mean diastolic blood pressure on the second days versus the first days in the laboratory (averaged across all diets). Collectively, the data suggest that elderly individuals with a high degree of chemical odor intolerance evidence (a) increased sympathetic tone in the cardiovascular system at rest over multiple measurements; and (b) greater sensitizability and/or lesser habituation of heart rate and diastolic blood pressure over time as a function, in part, of repeated environmental stressor exposures (i.e., a novel laboratory contextual setting and/or specific dietary constituents). Consistent with a sensitization model, the findings emphasize the need for two or more identical sessions at least 24 h apart in physiological studies of individuals with a high degree of intolerance for chemical odors versus normal individuals. The results of the blood pressure observations suggest that the possibility of abnormally labile autonomic function and cognitive sequelae in individuals with a high degree of intolerance for chemical odor increases with age.