Nature 427, 352 - 355 (22 January 2004);
Sleep inspires insight
wagner@kfg.uni-luebeck.de or J.B.born@kfg.uni-luebeck.de
            Insight denotes a mental restructuring that leads to a sudden gain of explicit knowledge allowing qualitatively changed behaviour. Anecdotal reports on scientific discovery suggest that pivotal insights can be gained through sleep. Sleep consolidates recent memories and, concomitantly, could allow insight by changing their representational structure. Here we show a facilitating role of sleep in a process of insight. Subjects performed a cognitive task requiring the learning of stimulus-response sequences, in which they improved gradually by increasing response speed across task blocks. However, they could also improve abruptly after gaining insight into a hidden abstract rule underlying all sequences. Initial training establishing a task representation was followed by 8 h of nocturnal sleep, nocturnal wakefulness, or daytime wakefulness. At subsequent retesting, more than twice as many subjects gained insight into the hidden rule after sleep as after wakefulness, regardless of time of day. Sleep did not enhance insight in the absence of initial training. A characteristic antecedent of sleep-related insight was revealed in a slowing of reaction times across sleep. We conclude that sleep, by restructuring new memory representations, facilitates extraction of explicit knowledge and insightful behaviour.

Public Library of Science Biology (online)

Volume 2 | Issue 1 | January 2004

Long-Lasting Novelty-Induced Neuronal Reverberation during Slow-Wave Sleep in Multiple Forebrain Areas

Sidarta Ribeiro1, Damien Gervasoni, Ernesto S. Soares, Yi Zhou1, Shih-Chieh Lin, Janaina Pantoja, Michael Lavine, Miguel A. L. Nicolelis      

            `The discovery of experience-dependent brain reactivation during both slow-wave (SW) and rapid eye-movement (REM) sleep led to the notion that the consolidation of recently acquired memory traces requires neural replay during sleep. To date, however, several observations continue to undermine this hypothesis. To address some of these objections, we investigated the effects of a transient novel experience on the long-term evolution of ongoing neuronal activity in the rat forebrain. We observed that spatiotemporal patterns of neuronal ensemble activity originally produced by the tactile exploration of novel objects recurred for up to 48 h in the cerebral cortex, hippocampus, putamen, and thalamus. This novelty-induced recurrence was characterized by low but significant correlations values. Nearly identical results were found for neuronal activity sampled when animals were moving between objects without touching them. In contrast, negligible recurrence was observed for neuronal patterns obtained when animals explored a familiar environment. While the reverberation of past patterns of neuronal activity was strongest during SW sleep, waking was correlated with a decrease of neuronal reverberation. REM sleep showed more variable results across animals. In contrast with data from hippocampal place cells, we found no evidence of time compression or expansion of neuronal reverberation in any of the sampled forebrain areas. Our results indicate that persistent experience-dependent neuronal reverberation is a general property of multiple forebrain structures. It does not consist of an exact replay of previous activity, but instead it defines a mild and consistent bias towards salient neural ensemble firing patterns. These results are compatible with a slow and progressive process of memory consolidation, reflecting novelty-related neuronal ensemble relationships that seem to be context- rather than stimulus-specific. Based on our current and previous results, we propose that the two major phases of sleep play distinct and complementary roles in memory consolidation: pretranscriptional recall during SW sleep and transcriptional storage during REM sleep.


J Neuropsychiatry Clin Neurosci 16:19-28, February 2004

Acupuncture Increases Nocturnal Melatonin Secretion and Reduces Insomnia and Anxiety: A Preliminary Report

D. Warren Spence, M.A., Leonid Kayumov, Ph.D., DABSM, Adam Chen, Ph.D., Alan Lowe, M.D., Umesh Jain, M.D., Martin A. Katzman, M.D., Jianhua Shen, M.D., Boris Perelman, Ph.D. and Colin M. Shapiro, MBBCh, Ph.D., FRCP(C); lkayumov@uhnres.utoronto.ca (E-mail).

            The response to acupuncture of 18 anxious adult subjects who complained of insomnia was assessed in an open prepost clinical trial study. Five weeks of acupuncture treatment was associated with a significant (p = 0.002) nocturnal increase in endogenous melatonin secretion (as measured in urine) and significant improvements in polysomnographic measures of sleep onset latency (p = 0.003), arousal index (p = 0.001), total sleep time (p = 0.001), and sleep efficiency (p = 0.002). Significant reductions in state (p = 0.049) and trait (p = 0.004) anxiety scores were also found. These objective findings are consistent with clinical reports of acupuncture's relaxant effects. Acupuncture treatment may be of value for some categories of anxious patients with insomnia.


Sleep Med. 2003 Jan;4(1):57-62.

A meta-analysis of sleep changes associated with placebo in hypnotic clinical trials.

McCall WV, D'Agostino R Jr, Dunn A. vmccall@wfubmc.edu

            OBJECTIVES: The effects associated with placebo (EAP) have been incompletely described in clinical trials of insomnia treatment. We conducted a meta-analysis of insomnia medication trials for the purpose of estimating the magnitude of sleep EAP. METHOD: We reviewed Medline for 1966 through 2000 for the meta-analysis. The subject heading of insomnia restricted to the subheading of drug therapy was crossed against the results of a search on the subjects heading placebo and text word placebo. We selected only papers that examined primary insomnia, incorporating both placebo and active medication therapies in a randomized, double-blind, parallel-group design. We required that results be reported for 1, 2, 3, or 4 weeks of treatment, and that outcomes be reported in hours/minutes. RESULTS: Five papers satisfied our requirements for eligibility, comprising 213 patients receiving placebo for a 2-week interval. Subjective sleep latency demonstrated a significant reduction (mean+/-S.E.) of 13.1+/-2.0 min (95% confidence interval (CI) 9.2, 17.0) for the placebo group after combining the data across studies. Subjective total sleep time demonstrated a significant increase of 13.5+/-5.4 min (95% CI 2.9, 24.0). Polysomnographic (PSG) sleep latency demonstrated a non-significant reduction of 2.5+/-4.3 min (95% CI -5.9, 10.9). CONCLUSIONS: The confirmation of EAP in insomnia clinical trials argues for the retention of a placebo control in future insomnia clinical trials.


Am J Psychiatry. 2002 Jan;159(1):5-11.

Comparative meta-analysis of pharmacotherapy and behavior therapy for persistent insomnia.

Smith MT, Perlis ML, Park A, Smith MS, Pennington J, Giles DE, Buysse DJ.


            OBJECTIVE: Although four meta-analytic reviews support the efficacy of pharmacotherapy and behavior therapy for the treatment of insomnia, no meta-analysis has evaluated whether these treatment modalities yield comparable outcomes during acute treatment. The authors conducted a quantitative review of the literature on the outcome of the two treatments to compare the short-term efficacy of pharmacotherapy and behavioral therapy in primary insomnia. METHOD: They identified studies from 1966 through 2000 using MEDLINE, psycINFO, and bibliographies. Investigations were limited to studies using prospective measures and within-subject designs to assess the efficacy of benzodiazepines or benzodiazepine receptor agonists or behavioral treatments for primary insomnia. Benzodiazepine receptor agonists included zolpidem, zopiclone, and zaleplon. Behavioral treatments included stimulus control and sleep restriction therapies. Twenty-one studies summarizing outcomes for 470 subjects met inclusion criteria. RESULTS: Weighted effect sizes for subjective measures of sleep latency, number of awakenings, wake time after sleep onset, total sleep time, and sleep quality before and after treatment were moderate to large. There were no differences in magnitude between pharmacological and behavioral treatments in any measures except latency to sleep onset. Behavior therapy resulted in a greater reduction in sleep latency than pharmacotherapy. CONCLUSIONS: Overall, behavior therapy and pharmacotherapy produce similar short-term treatment outcomes in primary insomnia





Aloia MS, Ilniczky N, Di Dio P, Perlis ML, Greenblatt DW, Giles DE. mark_aloia@brown.edu

Neuropsychological changes and treatment compliance in older adults with sleep apnea.

J Psychosom Res. 2003 Jan;54(1):71-6.

            INTRODUCTION: Apnea is a common disorder in older adults and has been shown to affect cognition. Some studies suggest that treatment for apnea improves certain cognitive deficits, but few studies have examined the relationship between compliance and cognitive improvement. We designed a study to answer the following questions about sleep apnea, cognition and treatment in older adults: (1) Which neuropsychological (NP) variables are differentially associated with measures of sleep fragmentation and oxygen desaturation? (2) Does compliant use of CPAP provide a cognitive advantage over noncompliant use? (3) Does NP performance at baseline predict compliance at 3 months? METHOD: Twelve participants were recruited for the study. All had polysomnographically defined sleep apnea with an RDI of 10 or greater. All were also at least 55 years of age, had no other diagnosable sleep disorder and had no previous treatment for sleep apnea syndrome (SAS). Participants were administered a full NP battery before and 3 months after treatment with CPAP. RDI at baseline was associated with delayed verbal recall, while oxygen desaturation was associated with both delayed recall and constructional abilities. Compliant use of CPAP at 3 months was associated with greater improvements in attention, psychomotor speed, executive functioning and nonverbal delayed recall. Finally, attention measures predicted compliance at 3 months suggesting that those who were least vigilant at baseline were more likely to comply with treatment. DISCUSSION: Results are discussed in terms of the relevance to targeting special populations for compliance interventions, the ways that treatment may specifically affect older adults and the possible dose-response relationship of CPAP.


Aldrich, M.S. (1999). Sleep Medicine, NY: Oxford University Press (Chapter 13 - Obstructive Sleep Apnea Syndrome). This chapter notes that complaints of poor memory or impaired attention are common in pts with OSA, and neuropsychological studies have shown impaired planning abilities, decreased ability to initiate new mental processes, and deficits of learning, memory, and attention. They note that these problems largely improve with treatment.

Aguirre M, Broughton R, Struss D. Does memory impairment exist in narcolepsy-cataplexy? J Clin Exp Neuropsychol 1985;7:14-24.


American Thoracic Society. Sleep apnea, sleepiness, and driving risk. Am J Respir Crit Care Med 1994;150:1463-1473.


Andreou G, Galanopoulou C, Gourgoulianis K, Karapetsas A, Molyvdas P.

Cognitive status in Down syndrome individuals with sleep disordered breathing deficits (SDB).

Brain Cogn. 2002 Oct;50(1):145-9.

            Twelve subjects with Down syndrome underwent polysomnographic studies during night sleep and performed the Mini-Mental state test and the Raven Progressive Matrices (RPM), sets A, B, and B(1). Sleep-disordered breathing (SDB) deficits were observed in Down syndrome individuals and their Mini-Mental and RPM scores were extremely low. Regression analysis of the results revealed that the number of apneas per hour was related with the results of the RPM, set A, which were also related with the orientation of Mini-Mental test, indicating that the more apneas an individual has the more difficulties he has in the kind of visuoperceptual skills, including orientation, associated with normal right hemisphere functioning, which are tested by set A of the RPM.


Archbold KH, Giordani B, Ruzicka DL, Chervin RD.  archbold@u.washington.edu

Cognitive executive dysfunction in children with mild sleep-disordered breathing.

Biol Res Nurs. 2004 Jan;5(3):168-76.

            In children, moderate or severe sleep-disordered breathing (SDB) may impair cognitive executive functions (EFs), including working memory, attention, and mental flexibility. The main objective of this study was to assess EFs in children with mild levels of SDB. Subjects for this descriptive study were 12 children (5 girls, 7 boys) aged 8.0 to 11.9 years (M = 9.0 +/- 0.85) participating in an ongoing study of the effects of adenotonsillectomy on behavior. Each subject had a nocturnal polysomnogram (PSG) and a multiple sleep latency test (MSLT). Mild SDB was considered present if the child's apnea/hypopnea index (AHI) was > or = 1 and < 10. Between MSLT nap attempts, each child completed standardized tests of EFs. The sample showed significant impairment of sustained attention and vigilance on a computerized continuous performance test. Children with low mental flexibility scores on the Children's Category Test (CCT) spent more time in stage 1 sleep (12.2% v. 9.5%, P = 0.028 on PSG) and showed a marginally higher arousal index (9.7 v. 6.5, P = 0.06 on PSG) than children with average or above-average CCT scores. AHI accounted for a significant proportion of the variance in CCT scores when 1 outlier was removed (N = 11, Rsq = 0.67, P = 0.002). Mild levels of SDB and associated sleep architecture disruptions may be associated with impairment of EFs in children.


Bearpark H, Grunstein R, Touyz S, Channon L, Sullivan C. Cognitive and psychological dysfunction in sleep apnea before and after treatment with CPAP. Sleep Res 1987;16:303.


Beullens J.

[Sleep and intellectual functioning in the elderly: the role of sleep quality and apnea--literature survey] [Article in Dutch]

Tijdschr Gerontol Geriatr. 2001 Aug;32(4):165-73.

            In both relatively healthy and in demented elderly people mental abilities and sleep quality decrease in becoming older and nocturnal respiratory disturbance increases. Perhaps there is an association between sleep and cognition. The hypothesis that specific sleep phenomena are necessary to assure an adequate level of cognitive functioning is called the sleep cognition hypothesis. In this article the findings of research in older people are reviewed. 23 research reports were found in which sleep was measured with polysomnography. The findings in relatively healthy older people do not suggest a strong association between sleep and cognition nor a causal effect between a specific cognitive dysfunction and a specific sleep variable. The findings in demented older people concerning sleep and cognition are inconsistent. In relatively healthy older people a significant correlation between nocturnal respiratory disturbance and cognitive functioning was seldom found, whereas in demented older people a clear association was shown. Therefore, in demented older people prudence is necessary in prescribing psychopharmaca because these can enhance the appearance of sleep apneas.


Bedard MA, Montplaisir J, Richer F, Rouleau I, Malo J.

Obstructive sleep apnea syndrome: pathogenesis of neuropsychological deficits.

J Clin Exp Neuropsychol. 1991 Nov;13(6):950-64.

            Neuropsychological deficits have been documented in patients with obstructive sleep apnea syndrome (OSAS). Both nocturnal hypoxemia and impairement of daytime vigilance have been suggested as the pathogenesis of these deficits, yet it remains difficult to find good correlations between cognitive deficits and either of these physiological parameters. In the present study, 10 normal controls were compared to 10 moderately and 10 severely apneic patients, all recorded in a sleep laboratory for two consecutive nights, with a vigilance and neuropsychological assessment made during the intervening day. Relative to the controls, moderate and severe OSAS showed differences in many cognitive functions, although the severely affected showed the greater differences. Moreover, severe apneics were also worse than moderate apneics on tests that were found to be normal in the latter group. This suggests a discontinuity in the appearance of neuropsychological deficits as OSAS progresses. Further analyses revealed that reductions in general intellectual measures, as well as in executive and psychomotor tasks were all attributable to the severity of hypoxemia, while other attention and memory deficits were related to vigiLance impairment. Therefore, both vigilance impairment and nocturnal hypoxemia may differentially contribute to the cognitive dysfunctions found in OSAS.


Bedard M-A, Montplaisir J, Malo J, Richler F, Rouleau I. Persistent neuropsychological deficits and vigilance impairment in sleep apnea syndrome after treatment with continuous positive airways pressure (CPAP). J Clin Exp Neuropsychol 1993;15:330-41.


Beebe DW, Gozal D.  dean.beebe@chmcc.org

Obstructive sleep apnea and the prefrontal cortex: towards a comprehensive model linking nocturnal upper airway obstruction to daytime cognitive and behavioral deficits.

J Sleep Res. 2002 Mar;11(1):1-16.

            Obstructive sleep apnea (OSA) is accompanied by significant daytime cognitive and behavioral deficits that extend beyond the effects of sleepiness. This article outlines a causal model by which to understand these psychological effects among OSA patients. The model proposes that sleep disruption and blood gas abnormalities prevent sleep-related restorative processes, and further induce chemical and structural central nervous system cellular injury. This, in turn, leads to dysfunction of prefrontal regions of the brain cortex (PFC), manifested behaviorally in what neuropsychologists have termed 'executive dysfunction'. Executive dysfunction is proposed to markedly affect the functional application of cognitive abilities, resulting in maladaptive daytime behaviors. The proposed model (1) accounts for the specific psychological phenotype associated with OSA, (2) accommodates developmental components in this phenotype, (3) bridges between physical and psychological phenomena, (4) suggests mechanisms by which the nocturnal disorder might have effects on daytime functioning, (5) is empirically testable, (6) generates unique research hypotheses, and (7) has practical implications. The model is intended to act as a catalyst for future research and as a preliminary guide for clinicians.


Beebe DW, Groesz L, Wells C, Nichols A, McGee K.  dean.beebe@cchmc.org

The neuropsychological effects of obstructive sleep apnea: a meta-analysis of norm-referenced and case-controlled data.

Sleep. 2003 May 1;26(3):298-307.

            STUDY OBJECTIVES: The research literature on the neuropsychological effects of obstructive sleep apnea (OSA) has yielded seemingly contradictory findings, and narrative reviews of this literature are prone to interpretive errors. We used sophisticated meta-analytic models to minimize such errors, with the goal of clarifying the effect of OSA on neuropsychological functioning. DESIGN: Meta-analytic review of research through 2001. PARTICIPANTS: We reviewed studies of neuropsychological functioning among adults with untreated OSA. Twenty-five studies met review criteria, representing 1092 patients with OSA and 899 healthy controls. MEASUREMENTS AND RESULTS: Two sets of effect sizes were generated. One compared OSA group means against those of healthy controls in case-controlled studies. The other compared all OSA group means against published normative data. Within each data set, 10 neuropsychological outcome domains were coded. In both data sets, untreated OSA was found to have a negligible impact on intellectual and verbal functioning but a substantial impact upon vigilance and executive functioning. Data were mixed with regard to visual and motor functioning; posthoc inspection of the data suggested that tests of fine-motor coordination or drawing were more sensitive to OSA than were tests of fine-motor speed or visual perception. Data were also mixed with regard to memory functioning, probably related to methodologic differences across studies. CONCLUSIONS: Etiologic models should emphasize mechanisms known to affect vigilance, executive functioning, and motor coordination but not intelligence, verbal functioning, or visual perception. Clinicians should be alert to OSA symptoms in patients with declines in vigilance, executive functioning, or coordination.


Berry DTR, Webb WB, Block AJ, Bauer RM, Switzer DA. Nocturnal hypoxia and neuropsychological variables. J Clin Exp Neuropsychol 1986;8:229-38.


Boland LL, Shahar E, Iber C, Knopman DS, Kuo TF, Nieto FJ;

Measures of cognitive function in persons with varying degrees of sleep-disordered breathing: the Sleep Heart Health Study.

J Sleep Res. 2002 Sep;11(3):265-72.

            Epidemiologic literature suggests that persons with clinically diagnosed sleep apnoea frequently have impaired cognitive function, but whether milder degrees of sleep-disordered breathing (SDB) are associated with cognitive dysfunction in the general population is largely unknown. Approximately 1700 subjects free of clinically diagnosed SDB underwent at-home polysomnography (PSG) as part of the Sleep Heart Health Study (SHHS) and completed three cognitive function tests within 1-2 years of their PSG: the Delayed Word Recall Test (DWR), the WAIS-R Digit Symbol Subtest (DSS), and the Word Fluency test (WF). A respiratory disturbance index (RDI) was calculated as the number of apnoeas and hypopnoeas per hour of sleep. After adjustment for age, education, occupation, field centre, diabetes, hypertension, body-mass index, use of CNS medications, and alcohol drinking status, there was no consistent association between the RDI and any of the three cognitive function measures. There was no evidence of a dose-response relation between the RDI and cognitive function scores and the adjusted mean scores by quartiles of RDI never differed from one another by more than 5% for any of the tests. In this sample of free-living individuals with mostly mild to moderate levels of SDB, the degree of SDB appeared to be unrelated to three measures of cognitive performance.


Broughton RJ, Fleming JAE, George CFP, Hill JD, Kryger MH, et al. Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy. Neurology 1997;49:444-51.


Cassel W, Ploch T, Becker C, Dugnus D, Peter JH, von Wichert P. Risk of traffic accidents in patients with sleep-disordered breathing: reduction with nasal CPAP. Eur Respir J 1996;9:2606-2611.


Cheshire, K; Engleman, H; Deary, Shapiro, C; Douglas, NJ. (1992). Factors impairing daytime performance in patients with sleep apnea/hypopnea syndrome. Arch Intern Med, Vol 152, March, 538-541. This aritcle found that deterioration of cognitive performance correlated significantly with increasing severity of nocturnal breathing irregularity, magnitude of nocturnal hypoxemia, and extent of sleep disruption. Both apneas/hypopneas per hour and lowest oxygen saturation were independently associated with IQ decrement.


Cohen-Zion M, Stepnowsky C, Marler, Shochat T, Kripke DF, Ancoli-Israel S.

Changes in cognitive function associated with sleep disordered breathing in older people.

J Am Geriatr Soc. 2001 Dec;49(12):1622-7.

            OBJECTIVES: Sleep disordered breathing (SDB) is very common in older people and is known to be associated with complaints of impaired daily functioning, including excessive daytime sleepiness and cognitive impairments. As part of a larger study on SDB and aging, it became possible to examine the relationship between SDB and cognition in older men and women. DESIGN: A population-based longitudinal study. SETTING: In-home interviews and home sleep recordings in the greater San Diego area. PARTICIPANTS: Community-dwelling people age 65 and older with high risk for SDB were originally studied from 1981 through 1985 and then followed every 2 years. Data from the 46 subjects who completed Visit 3 and Visit 4 are presented. MEASUREMENTS: Subjects were interviewed in the home about their sleep and medical condition before each visit. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Daytime sleepiness was based on self-report. Objective sleep was recorded in the home and scored for sleep, apneas and hypopneas, and oximetry variables. RESULTS: Increases in respiratory disturbance index (RDI) (P= .036) and increases in daytime sleepiness (P= .002) were associated with decreases in cognitive performance (i.e., increases in cognitive impairment). Increases in RDI were also associated with increases in daytime sleepiness (P= .012). Change in MMSE scores was therefore regressed onto changes in RDI, daytime sleepiness, age, and education, resulting in decreases in MMSE scores being associated with increases in daytime sleepiness (P= .019) but not with changes in RDI (P= .515). There was no significant relationship between changes in oxygen saturation levels and changes in MMSE. CONCLUSIONS: The results of this study suggest that declining cognitive function is associated primarily with increases in daytime sleepiness. Although cognitive decline was also associated with increases in RDI, this association did not hold in the more inclusive model which also included variable of SDB, oximetry, sleep and subjective report. One theoretical model could suggest that any relationship between SDB and cognitive function may be mediated by the effect of SDB on daytime sleepiness. These results suggest that older patients suffering from mild to moderate SDB may benefit from the treatment of SDB, even if they are not markedly hypoxemic.


Engleman, H.M., Cheshire, K.E., Deary, I.J., & Douglas, N.J. (1993). Daytime sleepiness, cognitive performance and mood after continuous positive airway pressure for the sleep apnoea/hyponoea syndrome. Thorax, 48:911-914. This study found significant improvements in objective sleepiness and mood with CPAP but no evidence of major improvements in cognitive function.


Engleman HM, Kingshott RN, Martin SE, Douglas NJ. H.Engleman@ed.ac.uk

Cognitive function in the sleep apnea/hypopnea syndrome (SAHS).

Sleep. 2000 Jun 15;23 Suppl 4:S102-8.

            The magnitude, determinants and reversibility of cognitive deficits associated with the sleep apnea/hypopnea syndrome (SAHS) are of clinical and research interest. A quantitative overview of impairment effect sizes (ESs) from case-control studies of cognitive performance in SAHS suggests that deficits broadly worsen with disease severity, with large average values for attentional (ES approximately 1.0 SD units) and executive (ES approximately 0.9 SD units) cognitive scores, and moderate values for memory-related (ES approximately 0.6 SD units) performance scores. A study of determinants of cognitive outcomes conducted in 150 patients with SAHS (AHI 5+ and > or =2 symptoms) showed significant but weak associations between a cognitive 'intellectual ability' component score (CS) and both AHI (r=-0.14) and minimum oxygen saturation (r = 0.15), linking increasing disease severity with poorer performance. A somewhat stronger correlation between a cognitive 'response slowing' CS and a 'wakefulness' CS was observed (r=-0.34). That sleepiness as well as hypoxemia might contribute to cognitive deficit has also been suggested by experimental sleep fragmentation in normals, producing small to moderate impairments (average ES approximately 0.3 SD units) in attention-biased scores. The reversibility of attentional cognitive deficits has been investigated through a meta-analysis of randomized placebo-controlled crossover studies of CPAP treatment, involving 98 SAHS patients (AHI 5+ and > or =2 symptoms). While cognitive outcomes showed at least trends towards better performance on CPAP than on placebo (p< or =0.1), the ESs of cognitive enhancements following CPAP were small (average ES approximately 0.2 SD units). This may be due either to the relatively mild study population, suboptimal CPAP use or to an irreversible component in cognitive impairment in SAHS.


Engleman HM, Martin SE, Deary IJ, Douglas NJ.

Effect of continuous positive airway pressure treatment on daytime function in sleep apnoea/hypopnoea syndrome.

Lancet. 1994 Mar 5;343(8897):572-5.

            Continuous positive airway pressure (CPAP) is the treatment of choice for the sleep apnoea/hypopnoea syndrome (SAHS); it is usually given with the aim of improving daytime cognitive function, mood, and sleepiness. However, its efficacy has not been validated by controlled trials. We have carried out a randomised, placebo-controlled, crossover study of objective daytime sleepiness, symptoms, cognitive function, and mood in a consecutive series of 32 SAHS patients with a median apnoea plus hypopnoea frequency of 28 (range 7-129) per hour slept. Patients were treated with 4 weeks each of CPAP and an oral placebo, which they were told might improve upper airway muscle function during sleep. Assessments on the last day of each treatment included a multiple sleep latency test and tests of symptom scores, mood profiles, and cognitive performance. The patients had significantly less daytime sleepiness on CPAP than during the placebo period (mean sleep latency 7.2 [SE 0.7] vs 6.1 [0.7] min, p = 0.03). There were also improvements with CPAP in symptom ratings (2.1 [0.2] vs 4.3 [0.3], p < 0.001), mood (p < 0.05 for several measures), and cognitive performance, which showed improved vigilance (obstacles hit in Steer Clear "driving" test 76 [5] vs 81 [6], p < 0.01), mental flexibility (trail-making B time 66 [5] vs 75 [5] s, p < 0.05), and attention (p < 0.05). Objectively monitored CPAP use averaged only 3.4 (0.4) hours per night, but this study provides evidence of improved cognitive performance even at this low level of CPAP compliance.


Ferini-Strambi L, Baietto C, Di Gioia MR, Castaldi P, Castronovo C, Zucconi M, Cappa SF. ferinistrambi.luigi@hsr.it

Cognitive dysfunction in patients with obstructive sleep apnea (OSA): partial reversibility after continuous positive airway pressure (CPAP).

Brain Res Bull. 2003 Jun 30;61(1):87-92.

            The aims of this study were to assess cognitive function in obstructive sleep apnea (OSA) patients and to evaluate the effect of short- and long-term treatment with continuous positive airway pressure treatment (CPAP). A battery of neuropsychological tests, the Epworth Sleepiness Scale (ESS), and the Beck Inventory Scale were administered to 23 patients with severe OSA (age: 56.5+/-6.13; AHI: 54.9+/-13.37) and to 23 age- and education-matched controls. The OSA patients were evaluated in a baseline condition and in two follow-up treatment sessions (after 15 days and 4 months of CPAP, respectively). At baseline, OSA patients had a significant impairment, compared to controls, in tests of sustained attention, visuospatial learning, executive function, motor performance, and constructional abilities. The longitudinal evaluation showed that after a 15-days CPAP treatment attentive, visuospatial learning, and motor performances returned to normal levels. A 4-months CPAP treatment did not result in any further improvement in cognitive tests. Performance on tests evaluating executive functions and constructional abilities was not affected by short- and long-term treatment with CPAP. The findings of this study confirm the hypothesis of partial reversibility of cognitive dysfunction in OSA patients after CPAP.


Findley LJ, Barth JT, Powers DC, Wilhoit SC, Boyd MS, Suratt PM. Cognitive impairment in patients with obstructive sleep apnea and associated hypoxemia. Chest 1986;90:686-90.


Findley LJ, Fabrizio MJ, Knight H, Norcross BB, Laforte AJ, Suratt PM. Driving simulator performance in patients with obstructive sleep apnea. Am Rev Respir Dis 1989;140(2):529-530.


Findley L, Unverzagt ME, Guchu R, Fabrizio M, Buckner J, Suratt P. Vigilance and automobile accidents in patients with sleep apnea or narcolepsy. Chest 1995;108(3):619-624.


Foley DJ, Masaki K, White L, Larkin EK, Monjan A, Redline S. foleyd@gw.nia.nih.gov

Sleep-disordered breathing and cognitive impairment in elderly Japanese-American men.

Sleep. 2003 Aug 1;26(5):596-9.

            STUDY OBJECTIVE: To assess the association between sleep-disordered breathing and cognitive functioning in an elderly cohort of Japanese-American men. DESIGN: Cross-sectional study. SETTING: The Honolulu-Asia Aging Study of Sleep Apnea, Oahu, Hawaii. PARTICIPANTS: 718 men between 79 and 97 years of age examined in 1999 and 2000. MEASUREMENTS: Apnea-hypopnea index from in-home overnight polysomnography, performance on the Cognitive Abilities Screening Instrument, body mass index, neck circumference, Epworth Sleepiness Scale, snoring, Center for Epidemiologic Studies Depression 11-item depression scale, physical disability, and history of heart disease, stroke, hypertension, diabetes, and dementia. RESULTS: Less than 30% of the men had no sleep-disordered breathing (apnea-hypopnea index < 5) and nearly one-fifth (19%) had severe sleep-disordered breathing (apnea-hypopnea index > or = 30). Severe sleep-disordered breathing was associated with higher body mass index, habitual snoring, and daytime drowsiness. No association was found between sleep-disordered breathing and cognitive functioning, including measures of memory function, concentration, and attention. CONCLUSIONS: Sleep-disordered breathing was associated with more drowsiness but not with poor performance on standardized cognitive tests used to screen for Alzheimer disease and other dementias in older persons. Because a healthy-participant effect may have contributed to this finding, more extensive cognitive testing may be necessary to reveal more subtle deficits from sleep-disordered breathing.


Friedman BC, Hendeles-Amitai A, Kozminsky E, Leiberman A, Friger M, Tarasiuk A, Tal A.

Adenotonsillectomy improves neurocognitive function in children with obstructive sleep apnea syndrome.

Sleep. 2003 Dec 15;26(8):999-1005.

            OBJECTIVE: To evaluate neurocognitive functions of children with obstructive sleep apnea syndrome (OSAS), before and after adenotonsillectomy, compared with healthy controls. DESIGN: Prospective study. PATIENTS AND METHODS: Thirty-nine children with OSAS aged 5 to 9 years (mean age, 6.8 +/- 0.2 years) and 20 healthy children (mean age, 7.4 +/- 1.4 years) who served as controls, underwent a battery of neurocognitive tests containing process-oriented intelligence scales. Twenty-seven children in the OSAS group underwent follow-up neurocognitive testing 6 to 10 months after adenotonsillectomy. Fourteen children in the control group were also reevaluated 6 to 10 months after the first evaluation. RESULTS: Children with OSAS had lower scores compared with healthy children in some Kaufman Assessment Battery for Children (K-ABC) subtests and in the general scale Mental Processing Composite, indicating impaired neurocognitive function. No correlation was found between neurocognitive performance and OSAS severity. Six to 10 months after adenotonsillectomy, the children with OSAS demonstrated significant improvement in sleep characteristics, as well as in daytime behavior. Their neurocognitive performance improved considerably, reaching the level of the control group in the subtests Gestalt Closure, Triangles, Word Order, and the Matrix analogies, as well as in the K-ABC general scales, Sequential and Simultaneous Processing scales, and the Mental Processing Composite scale. The magnitude of the change expressed as effect sizes showed medium and large improvements in all 3 general scales of the K-ABC tests. CONCLUSIONS: Neurocognitive function is impaired in otherwise healthy children with OSAS. Most functions improve to the level of the control group, indicating that the impaired neurocognitive functions are mostly reversible, at least 3 to 10 months following adenotonsillectomy.


Gale SD, Hopkins RO.  s2gale@chw.edu

Effects of hypoxia on the brain: neuroimaging and neuropsychological findings following carbon monoxide poisoning and obstructive sleep apnea.

J Int Neuropsychol Soc. 2004 Jan;10(1):60-71.

            Hypoxia damages multiple organ systems especially those with high oxygen utilization such as the central nervous system. The purpose of this study was to compare the neuropathological and neuropsychological effects of hypoxia in patients with either carbon monoxide poisoning or obstructive sleep apnea. Neuroimaging revealed evidence of hippocampal atrophy in both groups although a linear relationship between hippocampal volume and memory performance was found only for selected tests and only in the sleep apnea group. There were significant correlations between hippocampal volume and performance on measures related to nonverbal/information processing. Generalized brain atrophy, as measured by the ventricle-to-brain ratio, was more common in the carbon monoxide poisoning group compared to the obstructive sleep apnea group. Performance on tests of executive function improved following treatment with nasal continuous positive airway pressure treatment in the obstructive sleep apnea group but there was no associated improvement in general intellectual function. We found that hypoxia due to obstructive sleep apnea and CO poisoning resulted in neuropathological changes and neuropsychological impairments. The observed group differences provide insight into the relationship between etiology of injury, neuropathological changes, and clinical presentation


Gall R, Isaac L, Kryger M. Qaulity-of-life in mild obstructive sleep apnea. Sleep 1993;16:S59-61.


Gehrman PR, Martin JL, Shochat T, Nolan S, Corey-Bloom J, Ancoli-Israel S.

Sleep-disordered breathing and agitation in institutionalized adults with Alzheimer disease.

Am J Geriatr Psychiatry. 2003 Jul-Aug;11(4):426-33.

            OBJECTIVE: The authors examined the relationship between sleep-disordered breathing (SDB) and agitation in patients with Alzheimer disease (AD). METHODS: Thirty-eight AD patients (29 women, 9 men) in nursing homes in San Diego, CA participated. The mean age was 82.3 years, with a range of 61 to 95 years. Mean Mini-Mental State Exam score was 6.5 (range: 0-16). Sleep was recorded for one night, and agitation was measured with behavioral observations and ratings by nursing staff. RESULTS: SDB was very prevalent in this sample and was related to some types of agitation during the day but not in the evening or night. Aggressive Agitation on the Cohen-Mansfield Agitation Inventory and Manual Manipulation on the Agitated Behavior Rating Scale were greater with more severe SDB. Searching and wandering agitation decreased with more severe SDB. CONCLUSION: This study supports the hypothesis that SDB is related to agitation in AD, although the results are specific to certain types of agitation. Treatment of SDB may decrease agitation, easing the burden of caregiving and prolonging the time that patients are able to remain at home.


George CFP, Boudreau AC, Smiley A. Simulated driving performance in patients with obstructive sleep apnea. Am J Respir Crit Care Med 1996;154:175-81.


George C, Nickerson P, Hanly P, Millar T, Kryger M. Sleep apnea patients have more automobile accidents (Letter). Lancet 1987;i:447.


Greenberg GD, Watson RK, Deptula D. Neuropsychological dysfunction in sleep apnea. Sleep 1987;10:254-62.


Guilleminault C, Winkle R, Korobkin R, et al. Children and nocturnal snoring: evaluation of the effects of sleep related respiratory resistive load and daytime functioning. Eur J Pediatr 1982;139:165.


Hararldsson PO, Carefelt C, Persson HE, Sachs C, Tornros J. Simulated long-term driving performance before and after uvulopalatopharyngoplasty. ORL 1991;53:106-110.


Haraldsson PO, Carenfelt C, Tingvall C. Sleep apnea syndrome symptoms and automobile driving in a general population. J Clin Epidemiol 1992;45:821-825.


Hart RP, Morin CM, Best AM. Neuropsychological performance in elderly insomnia patients. Aging and Cognition 1995;2:268-78.


Hayward L, Mant A, Eyland A, Hewitt H, Purcell C, Turner J, et al. Sleep Disordered Breathing and Cognitive Function in a Retirement Village Population. Age and Ageing 1992;21:121-128.


Henry GK, Hart RP, Kwentus JA, Sicola MJ. Effects of protriptyline on vigilance and information processing in narcolepsy. Psychopharmacol 1988;95:109-12.


Henry GK, Satz P, Heilbronner RL. Evidence of a Perceptual-Encoding Deficit in Narcolepsy? Sleep 1993;16(2):123-27.


Kaneko Y, Hajek VE, Zivanovic V, Raboud J, Bradley TD.

Relationship of sleep apnea to functional capacity and length of hospitalization following stroke.

Sleep. 2003 May 1;26(3):293-7.

            STUDY OBJECTIVES: Recent evidence indicates that sleep apnea is common in patients with stroke. We hypothesized that the presence of sleep apnea among stroke patients would be associated with a greater degree of functional disability and longer hospitalization following stroke. DESIGN: Prospective study. SETTING AND PATIENTS: Sixty-one stroke patients admitted to a stroke rehabilitation unit. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Sleep studies were performed on all patients, and sleep apnea was defined as an apnea-hypopnea index of 10 or more per hour of sleep. Patients underwent functional assessments, including the Functional Independence Measure. Sleep apnea was found in 72% of patients; 60% had predominantly obstructive sleep apnea, while 12% had predominantly central sleep apnea. Although the severity of stroke was similar in the 2 groups, compared to patients without sleep apnea, those with sleep apnea had lower functional capacity [Functional Independence Measure score (mean +/- SEM) 80.2 +/- 3.6 versus 94.7 +/- 4.3, p < 0.05 at admission, and 101.5 +/- 2.8 versus 112.9 +/- 2.7, p < 0.05 at discharge] and spent significantly more days in rehabilitation (45.5 +/- 2.3 versus 32.1 +/- 2.7 days, p < 0.005). In addition, multiple regression analysis showed that obstructive sleep apnea was significantly and independently related to functional impairment and length of hospitalization. CONCLUSIONS: Sleep apnea is very common among stroke patients undergoing rehabilitation, and its presence is associated with worse functional impairment and a longer period of hospitalization and rehabilitation. These data suggest that sleep apnea may be contributing to functional impairment and prolonged hospitalization following stroke.


Kribbs NB, Pack AI, Kline LR, Getsy JE, Schuett JS, Henry JN, et al. Effects of one night without nasal CPAP treatment on sleep and sleepiness in patients with obstructive sleep apnea. Am Rev Respir Dis 1993;147:1162-8.


Levander S, Sachs C. Vigilance performance and autonomic function in narcolepsy: effects of central stimulants. Psychophysiol 1985;22:24-31.


Lind MG, Lundell BP. Tonsillar hyperplasia in children. A cause of obstructive sleep apneas, CO2 retention, and retarded growth. Arch Otolaryngol 1982;108:650.


Montplaisir J, Bedard MA, Richer F, Rouleau I. Neurobehavioral manifestations in obstructive sleep apnea syndrome before and after treatment with continuous positive airway pressure. Sleep 1992;15((Suppl)):S17-S19.


Naegele B, Thouvard V, Pepin J-L, Levy P, Bonnet C, Perret JE, et al. Deficits of Cognitive Executive Functions in Patients with Sleep Apnea Syndrome. Sleep 1995;18(1):43-52.


Newsom-Davis IC, Lyall RA, Leigh PN, Moxham J, Goldstein LH.

The effect of non-invasive positive pressure ventilation (NIPPV) on cognitive function in amyotrophic lateral sclerosis (ALS): a prospective study.

J Neurol Neurosurg Psychiatry. 2001 Oct;71(4):482-7.

            OBJECTIVES: Neuropsychological investigations have shown a degree of cognitive dysfunction in a proportion of non-demented patients with ALS. Respiratory muscle weakness in ALS can lead to nocturnal hypoventilation, resulting in sleep disturbance and daytime somnolence. Sleep deprivation of this type may cause impairments in cognitive function, but this has not been formally evaluated in ALS. METHODS: Cognitive functioning was evaluated in nine patients with ALS with sleep disturbance caused by nocturnal hypoventilation (NIPPV group), and in a comparison group of 10 similar patients without ventilation problems (control group). The NIPPV group then started non-invasive positive pressure ventilation (NIPPV) at night. After about 6 weeks, change in cognitive function was evaluated. RESULTS: Statistically significant improvement in scores on two of the seven cognitive tests was demonstrated in the NIPPV group postventilation, and a trend towards significant improvement was found for two further tests. Scores in the control group did not improve significantly for these four tests, although an improvement was found on one other test. CONCLUSIONS: Nocturnal hypoventilation and sleep disturbance may cause cognitive dysfunction in ALS. These deficits may be partially improved by NIPPV over a 6 week period. This has important implications for investigations of both cognitive dysfunction in non-demented patients with ALS, and the effect of ventilation on quality of life.


Redline S, Strauss ME, Adams N, Winters M, Roebuck T, Spry K, et al. Neuropsychological Function in Mild Sleep-Disordered Breathing. Sleep 1997;20(2):160-167.


Rouleau I, Decary A, Chicoine AJ, Montplaisir J.  rouleau.isabelle@uqam.ca

Procedural skill learning in obstructive sleep apnea syndrome.

Sleep. 2002 Jun 15;25(4):401-11.

            STUDY OBJECTIVES: To better characterize the cognitive deficits observed in obstructive sleep apnea syndrome (OSAS) by examining procedural skill learning abilities. DESIGN: Procedural skill learning was assessed using Mirror Tracing and Rotary Pursuit skill learning tasks. Subjects also completed a comprehensive neuropsychological test battery. SETTING: Cognitive testing was performed during the day following the second of two consecutive nights during which sleep and respiratory variables were recorded. PARTICIPANTS: Two groups (28 OSAS patients and 18 normal controls) with equivalent mean age and education levels. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: No significant differences in learning rates were observed between the groups on the Rotary Pursuit Task. On the Mirror Tracing Task, overall learning of the skill and transfer to a new figure or to the reverse tracing direction was similar in the OSAS and NC groups. However, there was a subgroup of OSAS subjects (n=11) who showed marked difficulties in the initial acquisition of the Mirror Tracing Task. This subgroup's performance was no longer significantly different from that of controls and OSAS subjects without initial adaptation difficulty in the subsequent trials. Performance of subjects who had difficulty with initial adaptation on the Mirror Tracing was also significantly lower on tests of frontal executive function, but not on episodic memory tests. Sleep and respiratory variables did not distinguish between the two subgroups of OSAS patients. However, none of the young OSAS subjects (<40 years) presented this deficit. CONCLUSION: Results indicate that contrary to this study's hypothesis, OSAS patients did not show procedural skill learning deficits. A subgroup of OSAS patients, however, did show deficits in initial skill adaptation and difficulties on other neuropsychological tests. Frontal dysfunction and decrement in psychomotor efficiency and vigilance appeared to be the most consistent explanation for characterizing the profile of neuropsychological test results among the OSAS patients.


Salorio CF, White DA, Piccirillo J, Duntley SP, Uhles ML.

Learning, memory, and executive control in individuals with obstructive sleep apnea syndrome.

J Clin Exp Neuropsychol. 2002 Feb;24(1):93-100.

            A range of neuropsychological deficits have been identified in individuals with obstructive sleep apnea syndrome (OSAS) and have been related to disruptions in function of the frontal cortex of the brain. We hypothesized that impairments in the use of strategic, frontally-mediated processes that facilitate learning and memory would be associated with deficits in the long-term episodic memory of verbal material (i.e., word lists). We evaluated 28 adults with OSAS and 24 controls (ranging from 28 to 60 years of age) using the California Verbal Learning Test. General executive abilities were assessed using the Wisconsin Card Sorting Test, Letter fluency, and Category fluency. Individuals with OSAS exhibited poorer recall across learning trials, less efficient use of semantic clustering, and poorer use of semantic cues. Retention of previously encoded information and recognition, however, were intact. With the exception of letter fluency, deficits were not observed in general executive control. Results are discussed within the context of disruptions in the interactions between long-term memory and executive abilities that are subserved by frontal and distal brain regions.


Sateia MJ.  michael.j.sateia@dartmouth.edu

Neuropsychological impairment and quality of life in obstructive sleep apnea.

Clin Chest Med. 2003 Jun;24(2):249-59.

            Although clinical experience has suggested for more than two decades that OSA is associated with impairment of cognition, emotional state, and quality of life and that treatment with nasal CPAP produces significant improvements in these areas, sound empirical evidence to support this view, especially regarding treatment outcome, has been lacking. More recent investigations have begun to provide this support from randomized, adequately controlled studies. These assessments suggest that some degree of cognitive dysfunction is associated with OSA. The effects are most apparent in the severe cases, whereas results in mild cases are more equivocal. Reported impairments include global intellectual dysfunction and deficits in vigilance, alertness, concentration, short- and long-term memory, and executive and motor function. Considerable discrepancy exists across studies with respect to type and degree of dysfunction, however. Disturbances in general intellectual function and executive function show strongest correlations with measures of hypoxemia. Not unexpectedly, alterations in vigilance, alertness, and, to some extent, memory seem to correlate more with measures of sleep disruption. Although many inadequately controlled investigations have demonstrated reversibility of most or all of these deficits with effective treatment, more recent placebo-controlled studies have raised doubts regarding whether the observed changes are truly a function of treatment. This issue requires further systematic exploration with adequate controls and step-wise analysis of treatment duration effects. A similar set of considerations exists with respect to the relationship between psychological disturbance, primarily depression, and OSA. Although several studies suggest significant depression in these patients, the results are mixed. Placebo-controlled treatment trials fail to demonstrate consistently a difference in mood improvement between active treatment groups and controls, although several methodologic considerations suggest that these results should be interpreted with caution. Numerous investigations leave little doubt about the issue of quality of life impairment among persons with OSA. Further characterization of impairment, particularly in areas specific to this population, will provide clearer understanding of the problem. Preliminary investigations of treatment response in controlled studies indicate significantly greater improvement of quality of life in response to CPAP. Although patients with OSA commonly report disturbances in cognitive and psychological function and general quality of life, the increased rates of obesity, hypertension, diabetes, cardiovascular disease, medication use, and related psychosocial complications present a host of potential etiologies that might explain the impairments noted. There can be little doubt that these covariants do, in some cases, contribute to neuropsychological dysfunctions. It is essential that future studies continue to define those disturbances that are specific to OSA, the relationship between levels of severity and impairment, the role of treatment in reversing these dysfunctions, and the correlation between test results and significant day-to-day social and occupational functional impairment.


Telakivi T, Kajaste S, Partinen M, Koskenvuo M, Slami T, Kaprio J. Cognitive function in middle-aged snorers and controls: role of excessive daytime somnolence and sleep related hypoxic events. Sleep 1988;11:454-62.


Valley V, Broughton R. Daytime performance deficits and physiological vigilance in untreated patients with narcolepsy-cataplexy compared to controls. Rev EEG Neurophysiol 1981;1:133-9.


Xu Y, Li S, Huang X, Cong B.

[Insulin-like growth factor-I and cognitive function in patients with obstructive sleep apnea syndrome] [Article in Chinese]

Zhonghua Yi Xue Za Zhi. 2002 Oct 25;82(20):1388-90.

            OBJECTIVE: To explore the possible biochemical mechanism of cognitive impairment in patients with obstructive sleep apnea syndrome (OSAS). METHODS: Polysomnography was administered to thirty-six patients with OSAS and eighteen education and BMI-matched controls, all males aged 40 approximately 49 for 8.5 hours at night. Early next morning blood was drawn and serum insulin-like growth factor-I (IGF-I) was determined by immunoradiometric assay. Then neuropsychological tests of visual regeneration, digital symbol, comprehensive memory and digital span were conducted. RESULTS: The quality of sleep in the patients with OSAS was significantly worse than that of the controls. The score of visual regeneration in the patients with OSAS was 8.4 +/- 2.7, significantly lower than that in control group (11.6 +/- 1.4, P < 0.01). The score of digital symbol in patients with OSAS was 36.92 +/- 8.31, significantly lower than that in the controls (47.8 +/- 6.8, P < 0.01). The serum IGF-I level of the patients with OSAS was: 127.2 +/- 87.0 ng/ml, significantly lower than that of the controls (194.03 ng/ml +/- 77.31 ng/ml, P < 0.05). The IGF-I level was significantly positively correlated with the scores of visual regeneration test (r = 0.381, P < 0.05) and digital symbol test (r = 0.330, P < 0.05), lowest SaO(2) (r = 0.371, P < 0.05), mean SaO(2) (r = 0.333, P < 0.05) and REM sleep duration (r = 0.598, P < 0.01). CONCLUSION: Decrease of serum IGF-I level may play a role in the cognitive impairment in patients with OSAS. Nocturnal hypoxemia and REM sleep deprivation may be the reason of the decrease of the serum IGF-I level in patients with OSAS.


5) www.websciences.org/sleepandhealth/kryger.html: This describes cognitive function in sleep disorders (by Meir H. Kryger) and notes that many studies from several countries have documented abnormalities in sleep apnea pts, including memory, learning, intellect, and a decreased ability to initiate new mental processes (i.e., planning).










Means MK, Lichstein KL, Edinger JD, Taylor DJ, Durrence HH, Husain AM, Aguillard RN, Radtke RA. mkmeans@duke.edu

Changes in depressive symptoms after continuous positive airway pressure treatment for obstructive sleep apnea.

Sleep Breath. 2003 Mar;7(1):31-42.

            It is generally believed that obstructive sleep apnea (OSA) causes depression in some patients, yet it is unknown whether this depression is an actual clinical phenomenon or purely a result of overlapping somatic/physical symptoms shared by both disorders. The present study investigated changes in both somatic and affective/cognitive symptoms of depression associated with the introduction of continuous positive airway pressure (CPAP) treatment for OSA. Participants were 39 outpatients (35 males, 4 females) with no current or past mental health problems, diagnosed with OSA in a hospital sleep disorders clinic. The Beck Depression Inventory (BDI) was administered prior to treatment and again 3 months after CPAP. Total BDI scores improved after CPAP, independent of objectively monitored CPAP compliance rates. Both somatic and affective/ cognitive symptoms of depression improved in a similar manner after treatment. Our findings suggest that depressive symptoms experienced by OSA patients are not solely the result of physical OSA symptoms but include a mood component as well. We introduce a hypothetical model to conceptualize the relationship between OSA and depression.




Pochat MD, Ferber C, Lemoine P.

[Depressive symptomatology and sleep apnea syndrome] [Article in French]

Encephale. 1993 Nov-Dec;19(6):601-7.

            The sleep apnea syndrome (SAS), which is defined by more than 5 apneas or hypopneas per hour of sleep (9), is quite a frequent affection which concerns 1.4 to 10% of general population (1.7). The major daytime complaints of the SAS are daytime sleepiness, memory and attention disorders, headaches and asthenia especially in the morning, and sexual impotence (9). The nocturnal manifestations are dominated by sonorous and generally long standing snoring, increased by dorsal decubitus and intake of alcohol, with repeated interruptions by respiratory arrests. These manifestations are always noted but rarely spontaneously reported. The sleep, non refreshing, is agitated and perturbed by numerous awakenings. The findings of the clinical examination are poor: obesity is found in 2/3 of the cases and arterial hypertension in 1/2 of the cases (20). Polygraphic recording during sleep only permits an absolute diagnosis. This frequent affection is a real problem of public health because of its numerous complications (3, 10, 12, 13, 18, 21). Symptoms of depression are often found when a patient with a SAS is examined and conversely, symptoms which evoke a SAS can be found in the clinical examination of depressed patients. We decided so to study the thymic and anxious status of 24 patients investigated for a SAS and submitted to a polygraphic recording during sleep. Four clinical parameters were studied: DSM III-R diagnosis criteria, Montgomery and Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HARS) and thymasthenia rating scale of Lecrubier, Payan and Puech. We also reported Total Sleep Time (TST = 6.5 +/- 1.5), Apnea Hypopnea Index (AHI = 26.7 +/- 21.6), number (2.1 +/- 2.8/h) and duration (174.2 +/- 150.8 s/h) of hypoxic events. Results showed that among 24 patients, 8 were depressed according to DSM III-R diagnosis criteria and had MADRS > 25, 22 were anxious, 11 had a major anxiety (HARS > 15) and 15 presented thymasthenia (SET > 15). Significative correlations existed between anxiety and depression (r = 0.82; p < 0.0001), depression and thymasthenia (r = 0.77; p < 0.0001) and thymasthenia and anxiety (r = 0.75; p < 0.0001). Among the 8 depressed patients a correlation existed between AHI and depression (r = 0.72; p = 0.04), but no correlation was found between depression and hypoxic events. These results were comparable to those of Guilleminault (10), Reynolds (21), Kales (12), Bliwise (3), Klonoff (13) and Millman (18) who studied relations between SAS and depression. The evaluation of thymasthenia gave a more precise typology of the depressive state associated to SAS: the type of the mood disorder is more "blunted" and "anhedonic" than "sorrowful", particularly characterised by asthenia, lack of energy, reduction of interests (leisures, libido, work), loss of initiative, difficulties to organise tasks, fall of performances and reduction of pleasure usually felt in pleasant events (15). The physic symptomatology dominated the psychic one. The sleep disorganization, more than metabolic consequences of apneas, could be involved in this associated depressive state. Other neuropsychiatric troubles can be associated to the SAS. In fact, cognitive troubles (2, 8, 14, 16, 19, 22, 24) and personality disorders (12, 18) have been described. Our data confirm previous observations suggesting a frequent association between SAS, depression, fatigue and anxiety. Clinicians should consequently be aware that a depression with severe complaints of fatigue should deserve an investigation oriented towards SAS. Conversely, when a SAS is diagnosed, it is necessary to look for a possible depression in order to set up the most appropriate treatment. The frequency of SAS, like depression's one, increases with age. Prescription and consummation of sedative psychotropic drugs increase too with age. Since respiratory depressant effects of these drugs have been clearly demonstrated, it is important to evoke SAS when depressive and/or anxious states are diagnosed and not to aggravate it. An efficacious treatment of SAS can also cure the associated depressive state, but this one can persist. It is necessary, in this case, to select a non sedative antidepressant.






Drummond SP, Brown GG, Gillin JC, Stricker JL, Wong EC, Buxton RB.

Altered brain response to verbal learning following sleep deprivation.

Nature. 2000 Feb 10;403(6770):655-7.

            The effects of sleep deprivation on the neural substrates of cognition are poorly understood. Here we used functional magnetic resonance imaging to measure the effects of 35 hours of sleep deprivation on cerebral activation during verbal learning in normal young volunteers. On the basis of a previous hypothesis, we predicted that the prefrontal cortex (PFC) would be less responsive to cognitive demands following sleep deprivation. Contrary to our expectations, however, the PFC was more responsive after one night of sleep deprivation than after normal sleep. Increased subjective sleepiness in sleep-deprived subjects correlated significantly with activation of the PFC. The temporal lobe was activated after normal sleep but not after sleep deprivation; in contrast, the parietal lobes were not activated after normal sleep but were activated after sleep deprivation. Although sleep deprivation significantly impaired free recall compared with the rested state, better free recall in sleep-deprived subjects was associated with greater parietal lobe activation. These findings show that there are dynamic, compensatory changes in cerebral activation during verbal learning after sleep deprivation and implicate the PFC and parietal lobes in this compensation.


Falleti MG, Maruff P, Collie A, Darby DG, McStephen M.  mfalleti@hotmail.com

Qualitative similarities in cognitive impairment associated with 24 h of sustained wakefulness and a blood alcohol concentration of 0.05%.

J Sleep Res. 2003 Dec;12(4):265-74.

            Previous studies that have quantified fatigue-related cognitive impairment as blood alcohol concentration (BAC) equivalents have been limited by two issues: the effect of practice on tests of cognition and, more importantly, the statistic used to quantify change in cognitive performance. The current study addressed these issues by adopting an ABACA design, which allowed for the adequate control of practice effects, and by using effect size metrics, which enabled direct comparisons to be made in performance impairments as a result of fatigue (i.e. sustained wakefulness of 24 h) and alcohol (i.e. BAC of 0.05%). Cognitive performance under the fatigue and alcohol conditions required the use of the CogState battery. It was demonstrated that fatigue caused greater impairment than alcohol on the speed of continuous attention and memory and learning, and on the accuracy of complex matching. Alcohol was more detrimental than fatigue only on the accuracy of memory and learning. Performances on the remaining tasks were the same for both the fatigue and alcohol conditions. These differences and similarities in performance impairment are discussed emphasizing the deleterious cognitive effects of relatively short periods of sustained wakefulness.


Forest G, Godbout R.

Effects of sleep deprivation on performance and EEG spectral analysis in young adults.

Brain Cogn. 2000 Jun-Aug;43(1-3):195-200.

            Nine totally sleep deprived (TSD) and nine control subjects were evaluated with a complete battery for attention and memory performance. Frontal and temporal EEGs (5 min, eyes closed) were also recorded before and after the night. TSD subjects exhibited three performance deficits: learning the Pursuit Rotor Task, implicit recall of paired words, and distractibility on the Brown-Peterson Test. Relative to evening recordings, control subjects showed decreased morning absolute powers in all electrodes for all frequencies except for Frontal delta; TSD subjects showed increased Frontal and Temporal theta and Frontal beta. These results show that motor procedural, implicit memory, and working memory are sensitive to one night of TSD, and that Frontal and Temporal theta spectral power seem to discriminate between a night with sleep from a night without.


Frey R, Decker K, Reinfried L, Klosch G, Saletu B, Anderer P, Semlitsch HV, Seidler D, Laggner AN. Richard.Frey@akh-wein.ac.at

Effect of rest on physicians' performance in an emergency department, objectified by electroencephalographic analyses and psychometric tests.

Crit Care Med. 2002 Oct;30(10):2322-9.

            OBJECTIVE: The aim of the field study was to objectify physicians' vigilance, well-being, and cognitive performance in the course of 24-hr shifts with and without afternoon rest. SUBJECTS, SETTING, AND DESIGN: Eleven residents (four women, seven men; age, 33.5 +/- 4.7 yrs) were observed when doing two regular 24-hr shifts at the emergency department (randomized crossover design): one without rest, the other with a period of rest in the early afternoon (duration, 2:31 +/- 1:04 hrs) and the opportunity of having a nap (duration, 1:07 +/- 0:26 hrs, n = 6). Electroencephalography and psychometric tests were carried out at 8 am and at midnight. MEASUREMENTS: Measurements included subjective perception of workload, stress, and sleeping behavior; computer-analyzed electroencephalography; adjective checklist (Eigenschaftsworterliste 60 S, a self-rating scale); complex reaction time test; Pauli test (number of calculations during 3 mins); and numerical memory test. RESULTS: Electroencephalographic analyses showed a significant decrease in alpha power and a significant increase in beta power in the evening as compared with the morning on both days. The nocturnal increase observed in delta activity was significantly less pronounced in duties with rest than in duties without rest. Physicians felt deactivated at night. The Eigenschaftsworterliste 60 S indicated deactivation at night and a rest-induced activation in the subgroup that had taken the opportunity to sleep in the afternoon. Psychometric tests did not show any significant differences, neither between performance in the morning and evening nor between results with and without rest. CONCLUSION: As expected, electroencephalographic recordings showed nocturnal deactivation and a vigilance-promoting effect of the afternoon rest. These objective findings were in accordance with the results derived from self-rating scales. On the other hand, in short-lasting psychometric tests, performance was found unchanged after 16 hrs of routine work. In further studies, a discrimination between resting periods with and without sleep will be important.


Halbach MM, Spann CO, Egan G.

Effect of sleep deprivation on medical resident and student cognitive function: A prospective study.

Am J Obstet Gynecol. 2003 May;188(5):1198-201.

            OBJECTIVE: The purpose of this study was to determine whether cognitive function test results decrease after a typical night of on-call duty, on the basis of the amount of sleep that is obtained. STUDY DESIGN: Two standard cognitive functions tests (the Grooved Pegboard and California Verbal Learning Test II) were administered to the 30 participants who were members of the obstetrics and gynecology house staff and to medical students at Emory University School of Medicine. Each test was administered twice, before and after on-call duty. The data were analyzed with a paired two-tailed Student t test. RESULTS: For the California Verbal Learning Test II, trial 5 showed a decrease in score of 0.8 (P =.05) after on-call duty. Trials 1 through 5 showed a decrease in score of 3.5 (P =.01). CONCLUSION: This finding suggests that cognitive function test scores do decrease after on-call duty. Scrutiny of this issue by the Accreditation Council of Graduate Medical Education is justified, and the issue should continue to be evaluated. Our finding suggests that a change in our current educational structure is warranted.


Kim DJ, Lee HP, Kim MS, Park YJ, Go HJ, Kim KS, Lee SP, Chae JH, Lee CT. kdj922@chollian.net

The effect of total sleep deprivation on cognitive functions in normal adult male subjects.

Int J Neurosci. 2001 Jul;109(1-2):127-37.

            This study was conducted to evaluate the effect of acute sleep deprivation on cognitive functions. A total of 18 healthy right handed males were deprived of sleep for 24 hours. Luria-Nebraska Neuropsychological Battery and calculation & digit-span subtest of K-WAIS were administered before and after sleep deprivation in order to examine the changes of cognitive functions. There were no differences in freedom from distractibility, tacile function, visual function, reading, writing, arithmetic and intellectual process function. However, the cognitive functions such as motor, rhythm, receptive & expressive speech, memory and complex verbal arithmetic function were decreased after sleep deprivation. All of these functions are known to be related to the right anterior hemisphere. For localization scales, the scores of right frontal and right temporal dysfunction scale were increased after sleep deprivation. These results indicate that sleep deprivation has a negative effect on cognitive functions, especially those associated with right anterior hemisphere or subcortical areas.


Lee HJ, Kim L, Suh KY.

Cognitive deterioration and changes of P300 during total sleep deprivation.

Psychiatry Clin Neurosci. 2003 Oct;57(5):490-6.

            The study was conducted to evaluate the cognitive deteriorations induced by sleep deprivation with the computerized neurocognitive tests and the P300 event-related potential. Thirty healthy college students (22 men, eight women) participated in the present study. Subjects remained awake for 38 h under continuous surveillance. In the morning and the evening of the two study days, the computerized neurocognitive tests and the P300 were performed. In vigilance test and reaction unit test, there were significant cognitive impairments during sleep deprivation. However, in the cognitrone test there was significant functional improvement, which might be due to the practice effect. The P300 latency was significantly prolonged and the amplitudes decreased during sleep deprivation. The cognitive impairment during 38 h of sleep deprivation was mainly in terms of vigilance and reaction time. In contrast, higher complex cognitive function such as fine perceptual analyses, visual discrimination and working memory might be not affected by 38 h of total sleep deprivation. The changes of P300 were significantly correlated with the results of vigilance and reaction unit tests but not with the cognitrone test. Taken together, these results suggest that the P300 changes that occur during sleep deprivation are a reflection of the decrement in vigilance, which prolongs reaction time.


Lieberman HR, Tharion WJ, Shukitt-Hale B, Speckman KL, Tulley R. harris.lieberman@na.amedd.army.mil

Effects of caffeine, sleep loss, and stress on cognitive performance and mood during U.S. Navy SEAL training. Sea-Air-Land.

Psychopharmacology (Berl). 2002 Nov;164(3):250-61. Epub 2002 Sep 05.

            RATIONALE: When humans are acutely exposed to multiple stressors, cognitive performance is substantially degraded. Few practical strategies are available to sustain performance under such conditions. OBJECTIVE: This study examined whether moderate doses of caffeine would reduce adverse effects of sleep deprivation and exposure to severe environmental and operational stress on cognitive performance. METHODS: Volunteers were 68 U.S. Navy Sea-Air-Land (SEAL) trainees, randomly assigned to receive either 100, 200, or 300 mg caffeine or placebo in capsule form after 72 h of sleep deprivation and continuous exposure to other stressors. Cognitive tests administered included scanning visual vigilance, four-choice visual reaction time, a matching-to-sample working memory task and a repeated acquisition test of motor learning and memory. Mood state, marksmanship, and saliva caffeine were also assessed. Testing was conducted 1 and 8 h after treatment. RESULTS: Sleep deprivation and environmental stress adversely affected performance and mood. Caffeine, in a dose-dependent manner, mitigated many adverse effects of exposure to multiple stressors. Caffeine (200 and 300 mg) significantly improved visual vigilance, choice reaction time, repeated acquisition, self-reported fatigue and sleepiness with the greatest effects on tests of vigilance, reaction time, and alertness. Marksmanship, a task that requires fine motor coordination and steadiness, was not affected by caffeine. The greatest effects of caffeine were present 1 h post-administration, but significant effects persisted for 8 h. CONCLUSIONS: Even in the most adverse circumstances, moderate doses of caffeine can improve cognitive function, including vigilance, learning, memory, and mood state. When cognitive performance is critical and must be maintained during exposure to severe stress, administration of caffeine may provide a significant advantage. A dose of 200 mg appears to be optimal under such conditions.


Owen G, Turley H, Casey A. Gail.Owen@Unilever.com

The role of blood glucose availability and fatigue in the development of cognitive impairment during combat training.

Aviat Space Environ Med. 2004 Mar;75(3):240-6.

            INTRODUCTION: The aim of this study was to determine whether inadequate nutrition would produce a reduction in the blood glucose concentration and impair cognitive function. METHODS: Energy intake, blood glucose, and cognitive function were measured in 18 male subjects during a 4-d military field exercise. Baseline measures of fasting blood glucose, body mass, cognitive function, and mood were taken before the start of combat training. Measurements of blood glucose, cognition, and well-being were then repeated during every subsequent 24 h period. Activity levels were monitored continuously using wrist-worn activity monitors. RESULTS: Subjects experienced an increase in symptoms relating to hypoglycemia after 24 h in the field (p < 0.01), vigor decreased (p < 0.001), and fatigue increased (p < 0.001). After 48 h, subjects reported feelings of depression (p < 0.05), anger (p < 0.01), and confusion (p < 0.001). Delayed memory recall was significantly impaired after 48 h (p < 0.05), and there was a decrease in vigilance (p < 0.01). Between 48 and 72 h, there was a decrease in immediate memory recall (p < 0.05). Delayed memory recall and vigilance remained impaired, but did not deteriorate further. When subjects were extracted from the field after 96 h, nude BM had decreased by 2% (p < 0.05). CONCLUSION: Although it was possible to reproduce the symptoms and cognitive impairment associated with hypoglycemia, there was no change in blood glucose concentration throughout the 4-d period. The impairment in cognitive function is likely to have been the result of significant sleep deprivation.


Pilcher JJ, Huffcutt AI.

Effects of sleep deprivation on performance: a meta-analysis.

Department of Psychology, Bradley University, Peoria, Illinois 61625, USA.

Sleep. 1996 May;19(4):318-26.

            To quantitatively describe the effects of sleep loss, we used meta-analysis, a technique relatively new to the sleep research field, to mathematically summarize data from 19 original research studies. Results of our analysis of 143 study coefficients and a total sample size of 1.932 suggest that overall sleep deprivation strongly impairs human functioning. Moreover, we found that mood is more affected by sleep deprivation than either cognitive or motor performance and that partial sleep deprivation has a more profound effect on functioning than either long-term or short-term sleep deprivation. In general, these results indicate that the effects of sleep deprivation may be underestimated in some narrative reviews, particularly those concerning the effects of partial sleep deprivation.


Sagaspe P, Charles A, Taillard J, Bioulac B, Philip P.

[Inhibition and working memory: effect of acute sleep deprivation on a random letter generation task] [Article in French]

Can J Exp Psychol. 2003 Dec;57(4):265-73.

            The literature contains inconsistent data on the effects of acute sleep deprivation on the superior cognitive functions. The primary purpose of this study is to determine the effectiveness of inhibition, one of the functions of the working memory executive centre (EC), over an extended, 36-hour waking period. Inhibition is a cognitive mechanism whereby individuals ignore non-relevant information recorded in their working memory. We also tested the effects of a 36-hour period of acute sleep deprivation on simple reaction time. Twelve young, healthy volunteers (M = 21.5 years, sigma = 2.3) performed a random generation task involving letters and a simple reaction time psychomotor test over four sessions held at 10-hour intervals. Each participant was assigned a "constant routine." Participants were kept awake in a prone position within a room whose environment was held strictly constant (light, noise, temperature, meals, etc.). This control procedure provided assurance that any variation in participant performance was solely caused by sleep deprivation. The random generation task, nearly two minutes in length, consisted in verbally producing a sequence of 100 letters in a random fashion (i.e. by inhibiting, for example, alphabetical order) and by keeping to a set rhythm. Our assumption was that capacity for inhibition diminished as the number of hours of sleep deprivation increased. The simple reaction test, 10 minutes in length, involved pressing a button as swiftly as possible to cause a black square to disappear from a screen. In this case our assumption was that acute sleep deprivation alters simple reaction time. Analysis of variance (ANOVA) through repeated measures using the "sessions" factor as an intra-subject variable showed no significant changes in randomization indices of the random generation task, contrary to analysis of average simple reaction times. Participants' reaction times deteriorated over the first two minutes of the test during the night they were deprived of sleep. It would seem that the contradictory results of previous studies of the effects of acute sleep deprivation on the inhibition function would be due to errors in factor identification. In conclusion, the inhibition function, as measured during the performance of a brief task, seems to remain intact during an extended, 36-hour waking period. Simple reaction time assessed by means of a brief psychomotor test is affected during a night of sleep deprivation. The working-memory inhibition executive function shows greater resistance to acute sleep deprivation than does psychomotor reaction time for the performance of short tasks.


Smith ME, McEvoy LK, Gevins A.  Michael@eeg.com

The impact of moderate sleep loss on neurophysiologic signals during working-memory task performance.

Sleep. 2002 Nov 1;25(7):784-94.

            STUDY OBJECTIVES: This study examined how sleep loss affects neurophysiologic signals related to attention and working memory. DESIGN: Subjective sleepiness, resting-state electroencephalogram, and behavior and electroencephalogram during performance of working-memory tasks were recorded in a within-subject, repeated-measures design. SETTING: Data collection occurred in a computerized laboratory setting. Participants: Sixteen healthy adults (mean age, 26 years; 8 female) Interventions: Data from alert daytime baseline tests were compared with data from tests during a late-night, extended-wakefulness session that spanned up to 21 hours of sleep deprivation. MEASUREMENTS AND RESULTS: Alertness measured both subjectively and electrophysiologically decreased monotonically with increasing sleep deprivation. A lack of alertness-related changes in electroencephalographic measures of the overall mental effort exerted during task execution indicated that participants attempted to maintain high levels of performance throughout the late-night tests. Despite such continued effort, responses became slower, more variable, and more error prone within 1 hour after participants' normal time of sleep onset. This behavior failure was accompanied by significant degradation of event-related brain potentials related to the transient focusing of attention. CONCLUSIONS: Moderate sleep loss compromises the function of neural circuits critical to subsecond attention allocation during working-memory tasks, even when an effort is made to maintain wakefulness and performance. Multivariate analyses indicate that combinations of working-memory-related behavior and neurophysiologic measures can be sensitive enough to permit reliable detection of such effects of sleep loss in individuals. Similar methods might prove useful for assessment of functional alertness in patients with sleep disorders.


Thomas M, Sing H, Belenky G, Holcomb H, Mayberg H, Dannals R, Wagner H, Thorne D, Popp K, Rowland L, Welsh A, Balwinski S, Redmond D. maria.thomas@na.amedd.army.mil

Neural basis of alertness and cognitive performance impairments during sleepiness. I. Effects of 24 h of sleep deprivation on waking human regional brain activity.

J Sleep Res. 2000 Dec;9(4):335-52.

            The negative effects of sleep deprivation on alertness and cognitive performance suggest decreases in brain activity and function, primarily in the thalamus, a subcortical structure involved in alertness and attention, and in the prefrontal cortex, a region subserving alertness, attention, and higher-order cognitive processes. To test this hypothesis, 17 normal subjects were scanned for quantifiable brain activity changes during 85 h of sleep deprivation using positron emission tomography (PET) and (18)Fluorine-2-deoxyglucose ((18)FDG), a marker for regional cerebral metabolic rate for glucose (CMRglu) and neuronal synaptic activity. Subjects were scanned prior to and at 24-h intervals during the sleep deprivation period, for a total of four scans per subject. During each 30 min (18)FDG uptake, subjects performed a sleep deprivation-sensitive Serial Addition/Subtraction task. Polysomnographic monitoring confirmed that subjects were awake. Twenty-four hours of sleep deprivation, reported here, resulted in a significant decrease in global CMRglu, and significant decreases in absolute regional CMRglu in several cortical and subcortical structures. No areas of the brain evidenced a significant increase in absolute regional CMRglu. Significant decreases in relative regional CMRglu, reflecting regional brain reductions greater than the global decrease, occurred predominantly in the thalamus and prefrontal and posterior parietal cortices. Alertness and cognitive performance declined in association with these brain deactivations. This study provides evidence that short-term sleep deprivation produces global decreases in brain activity, with larger reductions in activity in the distributed cortico-thalamic network mediating attention and higher-order cognitive processes, and is complementary to studies demonstrating deactivation of these cortical regions during NREM and REM sleep.


Wesensten NJ, Belenky G, Kautz MA, Thorne DR, Reichardt RM, Balkin TJ.


Maintaining alertness and performance during sleep deprivation: modafinil versus caffeine.

Psychopharmacology (Berl). 2002 Jan;159(3):238-47. Epub 2001 Oct 19.

            RATIONALE: The performance and alertness effects of modafinil were evaluated to determine whether modafinil should replace caffeine for restoring performance and alertness during total sleep deprivation in otherwise healthy adults. OBJECTIVES: Study objectives were to determine (a) the relative efficacy of three doses of modafinil versus an active control dose of caffeine 600 mg; (b) whether modafinil effects are dose-dependent; and (c) the extent to which both agents maintain performance and alertness during the circadian trough. METHODS: Fifty healthy young adults remained awake for 54.5 h (from 6:30 a.m. day 1 to 1:00 p.m. on day 3) and performance and alertness tests were administered bi-hourly from 8:00 a.m. day 1 until 10:00 p.m. day 2. At 11:55 p.m. on day 2 (after 41.5 h awake), subjects received double blind administration of one of five drug doses: placebo; modafinil 100, 200, or 400 mg; or caffeine 600 mg ( n=10 per group), followed by hourly testing from midnight through 12:00 p.m. on day 3. RESULTS: Performance and alertness were significantly improved by modafinil 200 and 400 mg relative to placebo, and effects were comparable to those obtained with caffeine 600 mg. Although a trend toward better performance at higher modafinil doses suggested a dose-dependent effect, differences between modafinil doses were not significant. Performance enhancing effects were especially salient during the circadian nadir (6:00 a.m. through 10:00 a.m.). Few instances of adverse subjective side effects (nausea, heart pounding) were reported. CONCLUSIONS: Like caffeine, modafinil maintained performance and alertness during the early morning hours, when the combined effects of sleep loss and the circadian trough of performance and alertness trough were manifest. Thus, equivalent performance- and alertness-enhancing effects were obtained with drugs possessing different mechanisms of action. However, modafinil does not appear to offer advantages over caffeine (which is more readily available and less expensive) for improving performance and alertness during sleep loss in otherwise normal, healthy adults.


Moderate sleep deprivation produces impairments in cognitive and motor performance equivalent to legally prescribed levels of alcohol intoxication.

Williamson AM, Feyer AM.  a.williamson@unsw.edu.au

Occup Environ Med. 2000 Oct;57(10):649-55.

            OBJECTIVES: To compare the relative effects on performance of sleep deprivation and alcohol. METHODS: Performance effects were studied in the same subjects over a period of 28 hours of sleep deprivation and after measured doses of alcohol up to about 0.1% blood alcohol concentration (BAC). There were 39 subjects, 30 employees from the transport industry and nine from the army. RESULTS: After 17-19 hours without sleep, corresponding to 2230 and 0100, performance on some tests was equivalent or worse than that at a BAC of 0.05%. Response speeds were up to 50% slower for some tests and accuracy measures were significantly poorer than at this level of alcohol. After longer periods without sleep, performance reached levels equivalent to the maximum alcohol dose given to subjects (BAC of 0. 1%). CONCLUSIONS: These findings reinforce the evidence that the fatigue of sleep deprivation is an important factor likely to compromise performance of speed and accuracy of the kind needed for safety on the road and in other industrial settings.




Predicting the short-term course of fatigue symptoms: Does adjustment of habitual coping strategies matter?    

Denise de Ridder ; Paul Leseman ; Angelique de Rijk           

British Journal of Health Psychology      Volume: 9 Part: 1 Page: 67 -- 80   

            The present study investigated whether adjustment of coping strategies would predict the six-week course of fatigue symptoms in a primary care sample (N = 221) and whether the contribution of adjusting coping strategies would depend on the duration of fatigue at the time. It was hypothesized that the motivation to adjust coping strategies would be most present in people who are confronted with the possibility of their symptoms turning into a chronic condition, and not in people who have been fatigued for either a short period or a very long period. Moreover, it was hypothesized that adjustments in the employment of coping strategies are a better predictor of fatigue course than the continued use of particular coping strategies. Using a prospective design with a six-week follow-up, the results of a multisample LISREL analysis over four groups of participants differing in fatigue duration showed that adjustment of coping strategies is a significant predictor of the course of fatigue symptoms, and that a differential effect related to fatigue duration is present. Findings are discussed in the context of the role of coping in regulating psychosomatic symptoms.



Aviat Space Environ Med. 2004 Mar;75(3):240-6.

The role of blood glucose availability and fatigue in the development of cognitive impairment during combat training.

Owen G, Turley H, Casey A.  Gail.Owen@Unilever.com

            INTRODUCTION: The aim of this study was to determine whether inadequate nutrition would produce a reduction in the blood glucose concentration and impair cognitive function. METHODS: Energy intake, blood glucose, and cognitive function were measured in 18 male subjects during a 4-d military field exercise. Baseline measures of fasting blood glucose, body mass, cognitive function, and mood were taken before the start of combat training. Measurements of blood glucose, cognition, and well-being were then repeated during every subsequent 24 h period. Activity levels were monitored continuously using wrist-worn activity monitors. RESULTS: Subjects experienced an increase in symptoms relating to hypoglycemia after 24 h in the field (p < 0.01), vigor decreased (p < 0.001), and fatigue increased (p < 0.001). After 48 h, subjects reported feelings of depression (p < 0.05), anger (p < 0.01), and confusion (p < 0.001). Delayed memory recall was significantly impaired after 48 h (p < 0.05), and there was a decrease in vigilance (p < 0.01). Between 48 and 72 h, there was a decrease in immediate memory recall (p < 0.05). Delayed memory recall and vigilance remained impaired, but did not deteriorate further. When subjects were extracted from the field after 96 h, nude BM had decreased by 2% (p < 0.05). CONCLUSION: Although it was possible to reproduce the symptoms and cognitive impairment associated with hypoglycemia, there was no change in blood glucose concentration throughout the 4-d period. The impairment in cognitive function is likely to have been the result of significant sleep deprivation.