The effect of sleep fragmentation on cognitive processing using computerized topographic brain mapping

Topographic brain mapping of evoked potentials can be used to localize abnormalities of cortical function. We evaluated the effect of sleep fragmentation on brain function by measuring the visual P300 waveform using brain mapping. Eight normal subjects (Epworth Score +/- SD: 5 +/- 3) underwent tone-induced sleep fragmentation and undisturbed study nights in a randomized cross-over design. Study nights were followed by topographic brain mapping using a visual information processing test and concurrent event-related potentials. Experimental sleep fragmentation did not significantly increase objective daytime sleepiness or lower cognitive performance on a battery of cognitive function tests (all P > or = 0.1). There were no significant topographical delays in P300 latencies with sleep fragmentation (all P > 0.15). However, at sites Fz, F4, T3, C3, Cz and C4 the P300 amplitudes were reduced significantly after sleep fragmentation (all P < 0.05). A reduction in P300 amplitude has previously been interpreted as a decrease in attention. These reductions in P300 amplitudes with sleep fragmentation in frontal, central and temporal brain areas suggest that sleep fragmentation may cause a broad decrease in attention. Sleep fragmentation did not delay P300 latencies in any brain area, and so does not explain the delay in P300 latencies reported in sleep apnoeics.     

The effect of in-laboratory polysomnography on sleep and objective daytime sleepiness

MSLT guidelines recommend performing MSLTs following polysomnography (PSG) to document the preceding night's sleep. We tested the hypothesis that patients are objectively sleepier after in-laboratory full diagnostic PSG than after a sleep recording at home. Sixteen patients with the sleep apnea/hypopnea syndrome (SAHS; AHI 35+/-SD 28 per hour slept) were recruited into a randomized crossover study. To monitor sleep with minimal disruption at home, only sleep was recorded on 2 consecutive nights, the first for acclimatization. The laboratory limb followed standard PSG. Both study nights were followed next day by MSLT and MWT. There were no differences in MSLT (12.0 SD 5.1 home, 11.6+/-4.7 min laboratory; p=0.7), MWT (32.7+/-8.7, 31.6+/-9.3 min; p=0.6) or total sleep time (362+/-53, 343+/-51 min; p=0.15) between home and laboratory limbs. However, on the home night, fewer microarousals (31+/-14, 54+/-25/hr slept; p<0.0001) and less % wake (15+/-10, 24+/-11; p=0.006) were found. On the home study night, patients had greater % REM sleep, slow-wave sleep and sleep efficiency (all p<0.009). This study does not support the hypothesis that patients are sleepier after laboratory PSG compared to home study night. However, the improved sleep at home raises the question whether laboratory-based polysomnography is always required prior to MSLT/MWT testing or whether less obtrusive monitoring of sleep duration at home would sometimes suffice.     

Association between nighttime sleep and napping in older adults

STUDY OBJECTIVES: Napping might indicate deficiencies in nighttime sleep, but the relationship is not well defined. We assessed the association of nighttime sleep duration and fragmentation with subsequent daytime sleep. DESIGN: Cross-sectional study. PARTICIPANTS: 235 individuals (47.5% men, 29.7% black), age 80.1 (2.9) years. MEASUREMENTS AND RESULTS: Nighttime and daytime sleep were measured with wrist actigraphy and sleep diaries for an average of 6.8 (SD 0.7) nights. Sleep parameters included total nighttime sleep (h), movement and fragmentation index (fragmentation), and total daytime sleep (h). The relationship of total nighttime sleep and fragmentation to napping (yes/no) was assessed using logistic regression. In individuals who napped, mixed random effects models were used to determine the association between the previous night sleep duration and fragmentation and nap duration, and nap duration and subsequent night sleep duration. All models were adjusted for age, race, gender, BMI, cognitive status, depression, cardiovascular disease, respiratory symptoms, diabetes, pain, fatigue, and sleep medication use. Naps were recorded in sleep diaries by 178 (75.7%) participants. The odds ratios (95% CI) for napping were higher for individuals with higher levels of nighttime fragmentation (2.1 [0.8, 5.7]), respiratory symptoms (2.4 [1.1, 5.4]), diabetes (6.1 [1.2, 30.7]), and pain (2.2 [1.0, 4.7]). Among nappers, neither sleep duration nor fragmentation the preceding night was associated with nap duration the next day. CONCLUSION: More sleep fragmentation was associated with higher odds of napping although not with nap duration. Further research is needed to determine the causal association between sleep fragmentation and daytime napping.     

A single night of sleep deprivation increases ghrelin levels and feelings of hunger in normal-weight healthy men

Sleep loss is currently proposed to disturb endocrine regulation of energy homeostasis leading to weight gain and obesity. Supporting this view, a reduction of sleep duration to 4 h for two consecutive nights has recently been shown to decrease circulating leptin levels and to increase ghrelin levels, as well as self-reported hunger. We hypothesized that similar endocrine alterations occur even after a single night of sleep restriction. In a balanced order, nine healthy normal-weight men spent three nights in our sleep laboratory separated by at least 2 weeks: one night with a total sleep time of 7 h, one night with a total sleep time of 4.5 h and one night with total sleep deprivation (SD). On a standard symptom-rating scale, subjects rated markedly stronger feelings of hunger after total SD than after 7 h sleep (3.9 ± 0.7 versus 1.7 ± 0.3; P  = 0.020) or 4.5 h sleep (2.2 ± 0.5; P  = 0.041). Plasma ghrelin levels were 22 ± 10% higher after total SD than after 7 h sleep (0.85 ± 0.06 versus 0.72 ± 0.04 ng mL⁻¹; P  = 0.048) with intermediate levels of the hormone after 4.5 h sleep (0.77 ± 0.04 ng mL⁻¹). Serum leptin levels did not differ between conditions. Feelings of hunger as well as plasma ghrelin levels are already elevated after one night of SD, whereas morning serum leptin concentrations remain unaffected. Thus, our results provide further evidence for a disturbing influence of sleep loss on endocrine regulation of energy homeostasis, which on the long run may result in weight gain and obesity.     

Age-Related Reduction in Daytime Sleep Propensity and Nocturnal Slow Wave Sleep

Objective:

To investigate whether age-related and experimental reductions in SWS and sleep continuity are associated with increased daytime sleep propensity.

Methods:

Assessment of daytime sleep propensity under baseline conditions and following experimental disruption of SWS. Healthy young (20-30 y, n = 44), middle-aged (40-55 y, n = 35) and older (66-83 y, n = 31) men and women, completed a 2-way parallel group study. After an 8-h baseline sleep episode, subjects were randomized to 2 nights with selective SWS disruption by acoustic stimuli, or without disruption, followed by 1 recovery night. Objective and subjective sleep propensity were assessed using the Multiple Sleep Latency Test (MSLT) and the Karolinska Sleepiness Scale (KSS).

Findings:

During baseline sleep, SWS decreased (P < 0.001) and the number of awakenings increased (P < 0.001) across the 3 age groups. During the baseline day, MSLT values increased across the three age groups (P < 0.0001) with mean values of 8.7min (SD: 4.5), 11.7 (5.1) and 14.2 (4.1) in the young, middle-aged, and older adults, respectively. KSS values were 3.7 (1.0), 3.2 (0.9), and 3.4 (0.6) (age-group: P = 0.031). Two nights of SWS disruption led to a reduction in MSLT and increase in KSS in all 3 age groups (SWS disruption vs. control: P < 0.05 in all cases).

Conclusions:

Healthy aging is associated with a reduction in daytime sleep propensity, sleep continuity, and SWS. In contrast, experimental disruption of SWS leads to an increase in daytime sleep propensity. The age-related decline in SWS and reduction in daytime sleep propensity may reflect a lessening in homeostatic sleep requirement. Healthy older adults without sleep disorders can expect to be less sleepy during the daytime than young adults.

Citation:

Dijk DJ; Groeger JA; Stanley N; Deacon S. Age-related reduction in daytime sleep propensity and nocturnal slow wave sleep. SLEEP 2010;33(2):211-223.     

A complementary relationship between wake and REM sleep in the auditory system: a pre-sleep increase of middle-ear muscle activity (MEMA) causes a decrease of MEMA during sleep

Since some evidence has supported a complementary relationship between waking and REM-sleep eye movement (variations in frequency, amplitude, or direction of waking saccades have been found to inversely affect the corresponding parameters of rapid eye movements), the present study assessed whether this relationship can also be shown for other phasic components of REM sleep, such as middle-ear muscle activity (MEMA), as a consequence of an increase of middle-ear reflex frequency during pre-sleep wake. Ten subjects were studied in three consecutive nights (one adaptation, one baseline, one experimental). In the experimental night, subjects underwent a 2-h pure-tone (1000 Hz, 90 dB SPL) auditory stimulation and MEMA was monitored every 15 min; noise exposure during daytime was also controlled. Results show that MEMA frequency during REM sleep significantly decreased during the experimental nights compared with baseline nights, while each sleep variable as well as mean daily auditory input did not present any significant difference between baseline and experimental nights. Results suggest that the complementary relationship between wake and REM sleep is not bounded to oculomotor activity, but it may also be extended at least to middle-ear muscle phasic activity. Received: 30 April 1999 / Accepted: 14 September 1999     

Effects of Acute 3, 4-Methylenedioxymethamphetamine on Sleep and Daytime Sleepiness in MDMA Users: A Preliminary Study

Study Objective:

3, 4-Methylenedioxymethamphetamine (MDMA) affects monoamine neurotransmitters that play a critical role in sleep and daytime alertness. However, the acute effects of MDMA on sleep and daytime sleepiness have not been studied under placebo-controlled conditions. This study was designed to establish the effects of acute MDMA or placebo administration and sleep restriction on sleep and daytime sleepiness.

Design:

Participants with a history of MDMA use were studied on 3 sessions of 3 nights (baseline, treatment, and recovery) and 2 days (following night 2 and 3) per session. On treatment nights (night 2), participants received placebo or 2 mg/kg of MDMA or underwent a restricted bed schedule with placebo. Sleep restriction was a positive control to compare sleep loss and consequent sleepiness associated with MDMA use. The scheduled sleep period was 8 hours long on nonrestricted nights, and standard sleep recordings and daytime sleepiness tests were conducted. Age-matched controls received 1 night and day of standard sleep and daytime sleepiness testing.

Setting:

Sleep laboratory

Participants:

Seven recreational MDMA-users and 13 matched control subjects.

Measurements and Results:

Acute MDMA shortened sleep primarily by increasing sleep latency, and it reduced stage 3/4 sleep and suppressed rapid eye movement (REM) sleep. The MDMA-reduced sleep time was not associated with increased daytime sleepiness the following day, as was seen in the sleep-restriction condition. Compared with control subjects, the MDMA users on the first night in the laboratory had shorter total sleep times and less stage 3/4 sleep. Average daily sleep latency on daytime sleepiness tests the day after nighttime placebo administration was increased in MDMA users compared with the control subjects, and MDMA users had an elevated number of sleep-onset REM periods on these tests, compared with control subjects.

Conclusions:

Acute MDMA administration disrupts sleep and REM sleep, specifically, without producing daytime sleepiness such as sleep restriction does. Compared with control subjects, recreational MDMA users showed evidence of hyperarousal and impaired REM function. The mechanism behind these effects is likely due to the deleterious effects of MDMA on catecholamines.^1–3

Citation:

Randall S; Johanson CE; Tancer M; Roehrs T. Effects of acute 3, 4-methylenedioxymethamphetamine on sleep and daytime sleepiness in MDMA users: a preliminary study. SLEEP 2009;32(11):1513-1519.     

Sleep tendency during extended wakefulness: insights into adolescent sleep regulation and behavior

Sleep tendency (latency to sleep onset) was examined during extended waking in prepubertal and mature adolescents to determine whether sleep pressure is lower near bedtime in the latter group. Participants were nine prepubertal (pubertal stage Tanner 1, mean age 11.1 years, SD+/-1.3 years, five males) and 11 pubertally mature adolescents (Tanner 5, 13.9+/-1.2 years, three males). They spent 10 nights at home on an identical fixed 10-h sleep schedule followed by a 36-h constant routine with sleep latency tests at 2-h intervals using standard polysomnography. Saliva was collected to assess dim-light melatonin onset (DLMO) phase. DLMO was earlier in the Tanner 1 (mean clock time=20:33 hours, SD=49 min) than Tanner 5 group (21:29 hours+/-42 min). Sleep latency compared at a 'critical period' spanning 12.5 (20:30 hours clock time) to 18.5 h (02:30 hours) after waking did not differ at 20:30 hours, but was shorter for the Tanner 1 group at 22:30 hours (Tanner 1=9.2+/-6.3 min; Tanner 5=15.7+/-5.8 min), 00:30 hours (Tanner 1=3.6+/-1.7 min; Tanner 5=9.0+/-6.4 min), and 02:30 hours (Tanner 1=2.0+/-1.7 min; Tanner 5=4.3+/-3.2 min; trend). These differences were apparent controlling for circadian phase by partial correlation. Sleep tendency after 14.5, 16.5, and 18.5 h awake was lower in mature versus prepubertal adolescents, supporting our hypothesis that a developmental change of intrinsic sleep-wake regulation may provide physiologically mediated 'permission' for later bedtimes in older adolescents.     

Behavioral Control of Respiration in Sleep and Sleepiness Due to Signal-Induced Sleep Fragmentation

The effects of sleep fragmentation on behavioral control of sleeping respiration and on daytime sleepiness were investigated in 20 college students. All were polygraphically monitored both during nighttime sleep and during daytime naps. Ten experimental subjects were informed while awake that tones would be presented to them during nighttime sleep. Their task was to terminate the tones by taking a deep breath. Half of the subjects first received tones every 4 min; the other half received them every 8 min. After 4 consecutive nights subjects received 3 days off and conditions were reversed for 4 more consecutive nights. Tones started at 45dB and, in the absence of a response, increased 10dB every 10 seconds up to 95dB. Control subjects (N = 10) did not receive tones. The absolute number of arousals to tones was greater but the percentage of arousals was lower under the 4-min condition. Full awakenings occurred infrequently. Probability of making a breathing response remained high across days for both fragmentation conditions, but latency to respond was shorter and probability higher under the 8-min condition. Sleep fragmentation, whether “frequent” (4-min) or “infrequent” (8-min), did not induce greater daytime sleepiness than did the nonfragmentation control condition, and sleepiness did not differ between the two experimental conditions. Implications for developing behavioral techniques for treating sleep-related breathing disorders are discussed.     

Effects of sleep fragmentation on the arousability to resistive loading in NREM and REM sleep in normal men

STUDY OBJECTIVE: In healthy subjects, arousability to inspiratory resistive loading is greater during rapid eye movement (REM) sleep compared with non-REM (NREM) sleep but is poorest in REM sleep in patients with sleep apnea. We therefore examined the hypothesis that sleep fragmentation impairs arousability, especially from REM sleep. DESIGN: Two blocks of 3 polysomnographies (separated by at least 1 week) were performed randomly. An inspiratory-loaded night followed either 2 undisturbed control nights (LN(C)) or 2 acoustically fragmented nights (LN(F)) SETTING: Sleep laboratory. PARTICIPANTS: Sixteen healthy men aged 20 to 29 years. INTERVENTIONS: In both loaded nights, an inspiratory resistive load was added via a valved facemask every 2 minutes during sleep and turned off either when arousal occurred or after 2 minutes. MEASUREMENTS AND RESULTS: During LN(F), arousability remained significantly greater in REM sleep (71% aroused within 2 minutes) compared with stage 2 (29%) or stage 3/4 (16%) sleep. After sleep fragmentation, arousability was decreased in stage 2 sleep (LN(F): 29%; LN(C): 38%; p < .05) and low in early REM sleep, increasing across the night (p < .01). In stage 3/4 sleep, neither an attenuation nor a change across the night was seen after sleep fragmentation. CONCLUSIONS: Mild sleep fragmentation is already sufficient to attenuate arousability in stage 2 sleep and to decrease arousability in early, compared with late, REM sleep. This means that sleep fragmentation affects the arousal response to increasing resistance and that the effects are different in stage 2 and REM sleep. The biologic reason for this increase in the arousal response in REM sleep across the night is not clear.     

Waking quantitative electroencephalogram and auditory event-related potentials following experimentally induced sleep fragmentation

STUDY OBJECTIVES: Experimental sleep fragmentation involves inducing arousals by administering intrusive auditory stimuli throughout the night. It is intended to model the frequent and periodic disruption experienced in common sleep disorders. Sleep fragmentation leads to daytime sleepiness, although evidence of performance impairment has been inconsistent. The purpose of this study was to investigate brain physiology associated with this level of sleep disruption. Specifically, quantitative analysis of electroencephalography was carried out, and auditory event-related potentials were recorded during daytime performance assessment following sleep fragmentation in good sleepers. DESIGN: Participants spent 4 consecutive 24-hour periods in the laboratory. On nights 2 and 3, sleep was fragmented using auditory stimuli that were delivered with increasing intensity until an arousal was noted. This design aimed to investigate the cumulative effects of sleep fragmentation on daytime functioning. SETTING: Data were collected in a sleep research laboratory during a 96-hour protocol. PARTICIPANTS: Eight healthy adults (mean age = 33.25) with no sleep complaints. MEASUREMENTS AND RESULTS: During the day, participants performed a 40-minute computerized test battery at 2-hour intervals (9:00 am -7:00 pm). The battery was presented in a fixed order and included measures of mood, sleepiness, reaction time, and serial addition or subtraction. Results indicated that subjective sleepiness and mood were impaired following sleep-fragmentation nights, compared to both baseline and recovery conditions. No performance deficits were apparent. The alpha:theta ratio, reflecting relative slowing of the electroencephalogram, was dramatically reduced following the second night of sleep fragmentation. Reductions in N1 amplitude of the event-related potentials indicated that attention was impaired with respect to early encoding processes following sleep fragmentation. CONCLUSIONS: Electroencephalographic and event-related potentials data illustrate impairment in information-processing capabilities associated with reduced arousal elicited by experimental sleep fragmentation. This subtle degree of sleep disruption, where total sleep time is not reduced, leads to sustained impairment in alertness and attention.     

Effect of sleep disruption on sleep, performance, and mood

Eleven young adult subjects were briefly awakened after each minute of electroencephalographic-defined sleep for 2 consecutive nights after undisturbed laboratory adaptation and baseline nights. Two undisturbed recovery nights followed disruption nights. On disruption nights, subjects were awakened with an audiometer and signaled the awakening by subjective rating of sleep state or button push response. The disruption procedure resulted in severely fragmented sleep with only very small amounts of slow-wave and REM sleep. Total sleep time was reduced by approximately 1 h on each night. Arousal threshold increased 56 dB across the disruption nights. Following disruption, subjects performed more poorly and rated themselves sleepier than on baseline. The level of decline was similar to that seen after periods of total sleep loss of 40-64 h. Recovery sleep was also similar to that seen after total sleep loss. It was concluded that periodic disruption of sleep, perhaps by destroying sleep continuity, quickly results in impaired function. These data may help explain function loss in severe sleep apneics.     

Tongue protrusion strength and fatiguability: relationship to apnoea/hypopnoea index and age

The sleep apnoea/hypopnoea syndrome (SAHS) is characterized by retroglossal or retropalatal narrowing. The site of obstruction, and the fact that negative pressure in the upper airway increases retroglossal airway size, suggests that tongue muscles may play a role in the maintenance of upper airway patency. We therefore hypothesized that tongue protrusion strength and fatiguability may be predictors of apnoea/hypopnoea index, vary with age and may be different in SAHS patients and normal subjects. Maximal strength (Fmax) and fatiguability (measured as the total time subjects were able to maintain 50% Fmax on three consecutive occasions separated by 30 s) were assessed using a force transducer in 98 consecutive apnoeic/hypopnoeic male patients referred to our laboratory for sleep studies [apnoea/hypopnoea index (AHI) range 3-130/h, age range 30-74 y]. Fmax and fatiguability were also compared in 15 male SAHS patients (mean AHI 20/h) and 15 nonsnoring male subjects matched for age, body mass index and fat free mass. A further 26 SAHS patients had tongue protrusion strength/fatiguability measured before, during and after a night's sleep. Log AHI was only weakly correlated with Fmax (r=- 0.21; P=0.03) and age (r=0.23; P=0.025), but not to fatiguability (P > 0.05). Comparison between SAHS and nonsnoring subjects did not demonstrate significant differences in Fmax (P=0.1) or fatiguability (P=0.1). There was no evidence of a change in muscle strength (P > 0.05) or fatigue (P > 0.05) during the course of a night's sleep. We conclude that tongue protrusion strength and fatiguability are unlikely to be important factors in the pathogenesis of SAHS.     

Increased homeostatic response to behavioral sleep fragmentation in morning types compared to evening types

STUDY OBJECTIVES: To evaluate the influence of chronotype on sleep stages and quantitative sleep EEG when sleep pressure is increased and sleep schedule remains constant. DESIGN: A 5-day session comprising an adaptation night, a baseline night, two nights of sleep fragmentation, and a recovery night. SETTING: Chronobiology laboratory. PARTICIPANTS: Twenty-four healthy subjects aged 19-34 years: 12 morning types and 12 evening types selected by questionnaire. Each group included 6 men and 6 women with a habitual sleep duration of 7 to 9 hours. Interventions: Two nights of behavioral sleep fragmentation induced by forced 5-min awakenings every half-hour. MEASUREMENTS AND RESULTS: Each night of polysomnography recording lasted 8 hours and was based on each subject's preferred sleep schedule. On both nights of sleep fragmentation, stage 1 sleep increased, while both total sleep time and minutes of slow wave sleep decreased. No difference was observed in sleep architecture between morning types and evening types during sleep fragmentation nights or during recovery night. Spectral analysis of all-night NREM sleep EEG showed that during the recovery night, morning types had a larger fronto-central increase in low frequency activities and a larger centro-parietal decrease in 14-15 Hz activity than evening types. The largest group difference was for slow wave activity in the fronto-central area during the first part of the sleep episode. CONCLUSIONS: These results add further support to a postulated difference in homeostatic sleep regulation between morning types and evening types, with morning types showing indications of a higher homeostatic response to sleep disruption.     

Effects of melatonin administration on daytime sleep after simulated night shift work

Disturbed sleep and on-the-job sleepiness are widespread problems among night shift workers. The pineal hormone melatonin may prove to be a useful treatment because it has both sleep-promoting and circadian phase-shifting effects. This study was designed to isolate melatonin's sleep-promoting effects, and to determine whether melatonin could improve daytime sleep and thus improve night time alertness and performance during the night shift. The study utilized a placebo-controlled, double-blind, cross-over design. Subjects (n=21, mean age=27.0 +/- 5.0 years) participated in two 6-day laboratory sessions. Each session included one adaptation night, two baseline nights, two consecutive 8-h night shifts followed by 8-h daytime sleep episodes and one recovery night. Subjects took 1.8 mg sustained-release melatonin 0.5 h before the two daytime sleep episodes during one session, and placebo before the daytime sleep episodes during the other session. Sleep was recorded using polysomnography. Sleepiness, performance, and mood during the night shifts were evaluated using the multiple sleep latency test (MSLT) and a computerized neurobehavioral testing battery. Melatonin prevented the decrease in sleep time during daytime sleep relative to baseline, but only on the first day of melatonin administration. Melatonin increased sleep time more in subjects who demonstrated difficulty in sleeping during the day. Melatonin had no effect on alertness on the MSLT, or performance and mood during the night shift. There were no hangover effects from melatonin administration. These findings suggest that although melatonin can help night workers obtain more sleep during the day, they are still likely to face difficulties working at night because of circadian rhythm misalignment. The possibility of tolerance to the sleep-promoting effects of melatonin across more than 1 day needs further investigation.     

Sleep and daytime sleepiness in retinitis pigmentosa patients

OBJECTIVE: We examined sleep, daytime sleepiness and the ability to stay awake during the day in patients affected with retinitis pigmentosa (RP), to further delineate the role of photoreceptors in the circadian cycle. METHODS: Twelve individuals diagnosed with RP (40 +/- 8 years) And 12 normally sighted healthy individuals (39 +/- 7 years) matched for age, body mass index (BMI) and sex were selected for the study. Participants had their sleep recorded on two consecutive nights and were monitored on the two following days. On the first day, their ability to stay awake and on the second, their sleep propensity were assessed using the Maintenance of Wakefulness Test (MWT) and the Multiple Sleep Latency Test (MSLT), respectively. Self-report measures were obtained using the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), and the Toronto Hospital Alertness Test (THAT). RESULTS: Subjective daytime sleepiness (ESS: 9 +/- 5 vs. 6 +/- 4, P=0.053) and objectively measured sleep propensity (MSLT: 10 +/- 5 vs. 17 +/- 3 min, P < 0.000) were significantly higher in RP patients than controls, whilst their alertness (THAT: 29 +/- 9 vs. 38 +/- 7, P=0.016) and ability to stay awake (MWT: 21 +/- 9 vs. 29 +/- 2 min, P=0.006) were significantly reduced. Retinitis pigmentosa participants had more disturbed nighttime sleep, with significantly more awakenings (arousal index: 14 +/- 8 vs. 8 +/- 6 h, P=0.039), and tended to have less rapid eye movement (REM) sleep (19 +/- 5 vs. 22 +/- 3%, P=0.094). CONCLUSION: Patients with RP have increased daytime sleepiness, reduced alertness and more disturbed nighttime sleep of poorer quality than their normally sighted counterparts, suggesting an influence of photoreceptor degeneration on the circadian cycle.     

Effect of zolpidem on the efficacy of continuous positive airway pressure as treatment for obstructive sleep apnea

STUDY OBJECTIVE: Assess the effect of the hypnotic zolpidem on the efficacy of nasal continuous positive airway pressure for treatment of Obstructive Sleep Apnea. DESIGN: Randomized double blind placebo controlled, cross-over study. SETTING: Veterans Administration Medical Center. PATIENTS: 16 patients with severe obstructive sleep apnea (apnea+ hypopnea index > 30/hr), on CPAP therapy for at least 6 months. INTERVENTION: Three sleep studies were performed over three consecutive weeks. On night one the pressure level required to prevent apnea, hypopnea, and snoring was determined. On the second and third study nights, either placebo (P) or 10 mg of zolpidem (Z) was given (random order) and subjects slept on the CPAP level determined on the first night. MEASUREMENTS: Sleep architecture, apnea + hypopnea index, arterial oxygen saturation. RESULTS: The sleep architecture was similar on the placebo and zolpidem nights except for a decrease in the sleep latency ( P: 23.5 +/- 4.7; Z: 13.1 +/- 3.3 minutes, P < 0.02) and a small decrease in the arousal index (P < 0.03) on zolpidem nights. The was no significant difference between placebo and zolpidem nights in the apnea + hypopnea index (P: 4.8 +/- 1.4 versus Z : 2.7 +/- 0.47 events/hour), oxygen desaturation index (1.46 +/- 0.53 versus 0.81 +/- 0.29 desaturations/hour), or the lowest SaO2 (91.4 +/- 0.6 versus 91.0 +/- 0.7%). CONCLUSIONS: Acute administration of zolpidem 10 mg does not impair the efficacy of an effective level of CPAP in patients with severe obstructive sleep apnea.     

Cumulative Effects of Sleep Restriction on Daytime Sleepiness

Sleep and daytime sleepiness were evaluated in 10 young adult subjects to determine whether restricting nocturnal step by a constant amount produces cumulative impairment. Subjects were studied for 12 consecutive days, including 3 baseline days with a 10-hr time in bed, 7 days with sleep restricted to 5 hrs, and 2 recovery days. In 5 subjects, recovery included a 10-hr time in bed; in the remaining subject, recovery induced a 5-hr time in bed with a 1-hr daytime nap. Sleepiness was measured using two self-rating scales and the multiple sleep latency test. During sleep restriction, nocturnal stage 2 and REM sleep were reduced and slow wave sleep was unaffected. Stanford Sleepiness Scales showed an immediate increase in daytime sleepiness that reached a plateau after 4 days. An analog sleepiness rating scale showed increased sleepiness after 2 restricted nights and leveled off after the fourth restricted night. The multiple sleep latency tests showed no effect of sleep restriction until the second day, followed by a progressive increase in sleepiness that persisted through the seventh sleep restriction day. During the recovery period, daytime sleepiness returned to basal values on all three measures following one full night of sleep; with a daytime nap, no further cumulative effects of sleep restriction were seen.     

Microarousals in patients with sleep apnoea/hypopnoea syndrome

SUMMARY Upper airway obstructions during sleep cause recurrent brief awakenings or microarousals. Standard criteria exist for sleep and respiratory event scoring, however, there are different definitions currently used to score microarousals. We therefore compared three definitions of microarousal (ranging from 1.5-3 s in duration) and one of awakening (> 15 s). We examined their occurrence at the termination of apnoeas and hypopnoeas and their correlation with daytime sleepiness in patients with sleep apnoea/hypopnoea syndrome (SAHS). Sixty-three patients (aged 49, SD 10) had overnight polysomnography, multiple sleep latency tests (MSLT) and Epworth Sleepiness Scales (ESS). There were significantly more microarousals by any definition than there were awakenings (P<0.001) and there were more 1.5 s than 3 s microarousals (P<0.001). Significantly more apnoeas and hypopnoeas were terminated by 1.5 s microarousals (83% and 81%) than by 3 s microarousals (75%) (all P<0.001). Apnoea/hypopnoea index (AHI) correlated significantly with objective daytime sleepiness (p = -0.30, P<0.01). There were weakly significant relationships between all three microarousal definitions (-0.24<P< -0.22, 0.03<P<0.04) and objective daytime sleepiness. None of the arousal definitions correlated with Epworth Sleepiness Scales scores. These results suggest that although 1.5 s microarousals are found at the end of more respiratory events, relationships between 3 and 1.5 s definitions, and daytime sleepiness are similar. This indicates that any of the three microarousal definitions can be used for visual assessment of sleep fragmentation.     

Zaleplon and zolpidem objectively alleviate sleep disturbances in mountaineers at a 3,613 meter altitude

STUDY OBJECTIVES: To assess the effects of zolpidem and zaleplon on nocturnal sleep and breathing patterns at altitude, as well as on daytime attention, fatigue, and sleepiness. DESIGN: Double-blind, randomized, placebo-controlled, cross-over trial. SETTING: 3 day and night alpine expedition at 3,613 m altitude. PARTICIPANTS: 12 healthy male trekkers. PROCEDURE: One week spent at 1,000 m altitude (baseline control), followed by 3 periods of 3 consecutive treatment nights (N1-3) at altitude, to test 10 mg zolpidem, 10 mg zaleplon, and placebo given at 21:45. MEASURES: Sleep from EEG, actigraphy and sleep logs; overnight arterial saturation in oxygen (SpO2) from infrared oximetry; daytime attention, fatigue and sleepiness from a Digit Symbol Substitution Test, questionnaires, and sleep logs; acute mountain sickness (AMS) from the Lake Louise questionnaire. RESULTS: Compared to baseline control, sleep at altitude was significantly impaired in placebo subjects as shown by an increase in the amount of Wakefulness After Sleep Onset (WASO) from 17 +/- 8 to 36 +/- 13 min (P<0.05) and in arousals from 5 +/- 3 to 20 +/- 8 (P<0.01). Slow wave sleep (SWS) and stage 4 respectively decreased from 26.7% +/- 5.8% to 20.6% +/- 5.8% of total sleep time (TST) and from 18.2% +/- 5.2% to 12.4% +/- 3.1% TST (P<0.05 and P<0.001, respectively). Subjects also complained from a feeling of poor sleep quality combined with numerous 02 desaturation episodes. Subjective fatigue and AMS score were increased. Compared to placebo control, WASO decreased by approximately 6 min (P<0.05) and the sleep efficiency index increased by 2% (P<0.01) under zaleplon and zolpidem, while SWS and stage 4 respectively increased to 22.5% +/- 5.4% TST (P<0.05) and to 15.0% +/- 3.4% TST (P<0.0001) with zolpidem only; both drugs further improved sleep quality. No adverse effect on nighttime SpO2, daytime attention level, alertness, or mood was observed under either hypnotic. AMS was also found to be reduced under both medications. CONCLUSIONS: Both zolpidem and zaleplon have positive effects on sleep at altitude without adversely affecting respiration, attention, alertness, or mood. Hence, they may be safely used by climbers.