W.F. Hofman

Age differences in sleep-wake behavior under natural conditions.

Differences in lifestyle may account for a considerable portion of the reported age-related changes in overt circadian rhythmicity. By instructing a group of healthy, noninstitutionalized, elderly subjects and a group of young adults to keep a sleep-wake log for a period of two weeks, and to wear an activity monitor for an overlapping period of 11 days, we attempted to assess age-related differences in the habitual sleep-wake behavior, in particular its day-to-day variability. Four clusters of coherent variables were constructed, reflecting (1) circadian phase, (2) variability of sleep-wake behavior, (3) sleep-wake continuity and (4) subjective sleep-wake quality. The results showed that, in comparison with the young subjects, the elderly had a relatively advanced and more regular sleep-wake pattern, reported more midnight awakening and did not differ in their subjective sleep evaluation. In spite of a greater regularity in their lifestyle (which would favor a larger amplitude of the overt circadian rhythmicity) oral temperature measurements showed some evidence of a weakened 24-h periodicity in the elderly.

Local sleep spindle modulations in relation to specific memory cues

Sleep spindles have been connected to memory processes in various ways. In addition, spindles appear to be modulated at the local cortical network level. We investigated whether cueing specific memories during sleep leads to localized spindle modulations in humans. During learning of word-location associations, words presented in the left and right visual hemifields were paired with different odors. By presenting a single odor during a subsequent nap, we aimed to selectively reactivate a subset of the studied material in sleeping subjects. During sleep, we observed topographically restricted spindle responses to memory cues, suggesting successful reactivation of specific memory traces. In particular, we found higher amplitude and greater incidence of fast spindles over posterior brain areas involved in visuospatial processing, contralateral to the visual field being cued. These results suggest that sleep spindles in different cortical areas reflect the reprocessing of specific memory traces.

Obstructive sleep apnea is related to impaired cognitive and functional status after stroke

STUDY OBJECTIVES Obstructive sleep apnea (OSA) is a common sleep disorder in stroke patients and is associated with prolonged hospitalization, decreased functional outcome, and recurrent stroke. Research on the effect of OSA on cognitive functioning following stroke is scarce. The primary objective of this study was to compare stroke patients with and without OSA on cognitive and functional status upon admission to inpatient rehabilitation. DESIGN Case-control study. SETTING AND PATIENTS 147 stroke patients admitted to a neurorehabilitation unit. INTERVENTIONS N/A. MEASUREMENTS All patients underwent sleep examination for diagnosis of OSA. We assessed cognitive status by neuropsychological examination and functional status by two neurological scales and a measure of functional independence. RESULTS We included 80 stroke patients with OSA and 67 stroke patients without OSA. OSA patients were older and had a higher body mass index than patients without OSA. OSA patients performed worse on tests of attention, executive functioning, visuoperception, psychomotor ability, and intelligence than those without OSA. No differences were found for vigilance, memory, and language. OSA patients had a worse neurological status, lower functional independence scores, and a longer period of hospitalization in the neurorehabilitation unit than the patients without OSA. OSA status was not associated with stroke type or classification. CONCLUSIONS Obstructive sleep apnea (OSA) is associated with a lower cognitive and functional status in patients admitted for stroke rehabilitation. This underlines the importance of OSA as a probable prognostic factor, and calls for well-designed randomized controlled trials to study its treatability.

Effects of Continuous Positive Airway Pressure on Cognitive and Functional Outcome of Stroke Patients with Obstructive Sleep Apnea : A Randomized Controlled Trial

STUDY OBJECTIVES Obstructive sleep apnea (OSA) in stroke patients is associated with worse functional and cognitive status during inpatient rehabilitation. We hypothesized that a four-week period of continuous positive airway pressure (CPAP) treatment would improve cognitive and functional outcomes. METHODS We performed a randomized controlled trial in stroke patients admitted to a neurorehabilitation unit. Patients were assigned to rehabilitation treatment as usual (control group) or to CPAP treatment (CPAP group). Primary outcomes were cognitive status measured by neuropsychological examination, and functional status measured by two neurological scales and a measure of activities of daily living (ADL). Secondary measures included sleepiness, sleep quality, fatigue, and mood. Tests were performed at baseline and after the four-week intervention period. RESULTS We randomly assigned 20 patients to the CPAP group and 16 patients to the control group. The average CPAP compliance was 2.5 hours per night. Patients in the CPAP group showed significantly greater improvement in the cognitive domains of attention and executive functioning than the control group. CPAP compliance was associated with greater improvement in cognitive functioning. CPAP did not result in measurable improvement on measures of neurological status or ADL, or on any of the secondary measures. CONCLUSIONS CPAP treatment improves cognitive functioning of stroke patients with OSA. COMMENTARY A commentary on this article appears in this issue on page 467.

Diagnostic Accuracy of Nocturnal Oximetry for Detection of Sleep Apnea Syndrome in Stroke Rehabilitation

Background and Purpose— Sleep apnea syndrome (SAS) is a common sleep disorder in stroke patients and is associated with decreased recovery and increased risk of recurrent stroke and mortality. The standard diagnostic test for SAS is poly(somno)graphy, but this is often not feasible in stroke rehabilitation settings. This study investigated the diagnostic value of nocturnal oximetry for screening SAS in stroke rehabilitation. Methods— Fifty-six stroke patients underwent nocturnal polygraphy and oximetry. Sensitivity, specificity, and positive and negative predictive values for the oxygen desaturation index were calculated. Patient and sleep characteristics were used to develop a predictive model of apnea–hypopnea index. Results— Forty-six percent of the stroke patients had SAS. The majority of SAS patients was male, older, and had a higher body mass index than patients without SAS. Sensitivity, specificity, and positive and negative predictive values for the oxygen desaturation index ≥15 were, respectively, 77%, 100%, 100%, and 83%. Oxygen desaturation index predicted 87% of the variance in the apnea–hypopnea index. Patient characteristics did not add significantly to the prediction model. Conclusion— Nocturnal oximetry is an accurate diagnostic screening instrument for the detection of SAS in stroke patients.

EEG Beta Power but Not Background Music Predicts the Recall Scores in a Foreign-Vocabulary Learning Task.

As tantalizing as the idea that background music beneficially affects foreign vocabulary learning may seem, there is—partly due to a lack of theory-driven research—no consistent evidence to support this notion. We investigated inter-individual differences in the effects of background music on foreign vocabulary learning. Based on Eysenck’s theory of personality we predicted that individuals with a high level of cortical arousal should perform worse when learning with background music compared to silence, whereas individuals with a low level of cortical arousal should be unaffected by background music or benefit from it. Participants were tested in a paired-associate learning paradigm consisting of three immediate word recall tasks, as well as a delayed recall task one week later. Baseline cortical arousal assessed with spontaneous EEG measurement in silence prior to the learning rounds was used for the analyses. Results revealed no interaction between cortical arousal and the learning condition (background music vs. silence). Instead, we found an unexpected main effect of cortical arousal in the beta band on recall, indicating that individuals with high beta power learned more vocabulary than those with low beta power. To substantiate this finding we conducted an exact replication of the experiment. Whereas the main effect of cortical arousal was only present in a subsample of participants, a beneficial main effect of background music appeared. A combined analysis of both experiments suggests that beta power predicts the performance in the word recall task, but that there is no effect of background music on foreign vocabulary learning. In light of these findings, we discuss whether searching for effects of background music on foreign vocabulary learning, independent of factors such as inter-individual differences and task complexity, might be a red herring. Importantly, our findings emphasize the need for sufficiently powered research designs and exact replications of theory-driven experiments when investigating effects of background music and inter-individual variation on task performance.

The effect of obstructive sleep apnea and treatment with continuous positive airway pressure on stroke rehabilitation: rationale, design and methods of the TOROS study

BackgroundObstructive sleep apnea is a common sleep disorder in stroke patients. Obstructive sleep apnea is associated with stroke severity and poor functional outcome. Continuous positive airway pressure seems to improve functional recovery in stroke rehabilitation. To date, the effect of continuous positive airway pressure on cognitive functioning in stroke patients is not well established. The current study will investigate the effectiveness of continuous positive airway pressure on both cognitive and functional outcomes in stroke patients with obstructive sleep apnea.Methods/DesignA randomized controlled trial will be conducted on the neurorehabilitation unit of Heliomare, a rehabilitation center in the Netherlands. Seventy stroke patients with obstructive sleep apnea will be randomly allocated to an intervention or control group (n = 2×35). The intervention will consist of four weeks of continuous positive airway pressure treatment. Patients allocated to the control group will receive four weeks of treatment as usual. Outcomes will be assessed at baseline, immediately after the intervention and at two-month follow-up.In a supplementary study, these 70 patients with obstructive sleep apnea will be compared to 70 stroke patients without obstructive sleep apnea with respect to cognitive and functional status at rehabilitation admission. Additionally, the societal participation of both groups will be assessed at six months and one year after inclusion.DiscussionThis study will provide novel information on the effects of obstructive sleep apnea and its treatment with continuous positive airway pressure on rehabilitation outcomes after stroke.Trial registrationTrial registration number: Dutch Trial Register NTR3412

Normal sleep and its neurophysiological regulation

Normal sleep consists of two states: NREM (light and deep sleep) and REM, alternating in a cyclical pattern. The sleep/wake rhythm is regulated by two processes: the sleep propensity, building up during wake, and the circadian rhythm, imposed by the suprachiasmatic nucleus. The arousal pathways in the brainstem regulate the wake state. The ventrolateral preoptic nucleus in the hypothalamus (VLPO) is important for the control of NREM sleep. The VLPO neurons and the arousal pathways mutually inhibit each other, resulting in the alternation between sleeping and waking. Orexin from the lateral hypothalamus may stabilize the switching between these states. Cells in the pons and mesencephalon bring about the main phenomena of REM sleep. Although the regulation of the alternation between REM and NREM is not yet clear a mutually inhibitory interaction has been proposed between NREM active (REM-off) neurons and REM active (REM-on) neurons in brainstem and midbrain.

Can a prediction model combining self-reported symptoms, sociodemographic and clinical features serve as a reliable first screening method for sleep apnea syndrome in patients with stroke?

OBJECTIVE To determine whether a prediction model combining self-reported symptoms, sociodemographic and clinical parameters could serve as a reliable first screening method in a step-by-step diagnostic approach to sleep apnea syndrome (SAS) in stroke rehabilitation. DESIGN Retrospective study. SETTING Rehabilitation center. PARTICIPANTS Consecutive sample of patients with stroke (N=620) admitted between May 2007 and July 2012. Of these, 533 patients underwent SAS screening. In total, 438 patients met the inclusion and exclusion criteria. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES We administered an SAS questionnaire consisting of self-reported symptoms and sociodemographic and clinical parameters. We performed nocturnal oximetry to determine the oxygen desaturation index (ODI). We classified patients with an ODI ≥15 as having a high likelihood of SAS. We built a prediction model using backward multivariate logistic regression and evaluated diagnostic accuracy using receiver operating characteristic analysis. We calculated sensitivity, specificity, and predictive values for different probability cutoffs. RESULTS Thirty-one percent of patients had a high likelihood of SAS. The prediction model consisted of the following variables: sex, age, body mass index, and self-reported apneas and falling asleep during daytime. The diagnostic accuracy was .76. Using a low probability cutoff (0.1), the model was very sensitive (95%) but not specific (21%). At a high cutoff (0.6), the specificity increased to 97%, but the sensitivity dropped to 24%. A cutoff of 0.3 yielded almost equal sensitivity and specificity of 72% and 69%, respectively. Depending on the cutoff, positive predictive values ranged from 35% to 75%. CONCLUSIONS The prediction model shows acceptable diagnostic accuracy for a high likelihood of SAS. Therefore, we conclude that the prediction model can serve as a reasonable first screening method in a stepped diagnostic approach to SAS in stroke rehabilitation.

The effect of an emotional film on sleep EEG: relation with emotional attenuation over sleep.

Objectives: The aim of this study was to move forward from: ‘‘snapshot’’ cognitive probe studies used to establish selective attention in insomnia and understand processing of salient sleep words over time within the context of approach and avoidance. Methods: The novel methodology to insomnia research, eye tracking, was used to monitor the eye movements of individuals with psychophysiological insomnia (PI) and good sleepers (GS) to sleep positive, sleep negative and neutral words over a three second period. Results: The data shows that individuals with insomnia are less accurate [F(1.39) = 4.6, P < .05], take longer to fixate on the target word [F(1.39) = 5.0, P < .05] and take longer to move from distractor to target word [F(1.39) = 3.9, P < .05]. There is a trend towards significance suggestive of faster processing of positive sleep words compared to sleep negative or neutral words [F(2.78) = 2.9, P = .07]. Conclusions: Irrespective of word salience, the PI would appear to show detrimental processing overall compared to GS. Interesting questions arise within this context of whether this is an artefact of fatigue or there is indeed a processing impairment. The trend toward faster processing of sleep positive words would suggest that there is a possible selective processing impairment.