Alain Besset

Sleep architecture, slow wave activity, and sleep spindles in adult patients with sleepwalking and sleep terrors

OBJECTIVES A very strong SWS intensity reflected by both an increased level of SWA and an abnormal sleep spindles distribution would be responsible for the major difficulty of parasomniac subjects in waking up from SWS, leading to episodes of parasomnia. METHODS Eleven adult parasomniac subjects, 6 females and 5 males, with sleepwalking (SW) and/or sleep terrors (ST) and 11 age- and sex-matched control subjects underwent polysomnography (PSG) during 2 consecutive nights. After an habituation and selection night followed by a 16 h period of controlled wakefulness, the sleep EEGs of the parasomniac and control subjects were analyzed on the second night by computer-aided visual scoring (integrated digital filtering analysis, IDFA) and spectral analysis (fast Fourier transform, FFT). Throughout the night subject behaviour was controlled and recorded by means of a video infra-red camera and videotape recorder. RESULTS Fifteen episodes of parasomnia were recorded during the second night in the 11 subjects. Sleep analysis showed significantly (P<0.05) decreased sleep efficiency and stage 2 sleep (absolute values and percentage of total sleep time) and increased (P<0.05) slow wave sleep (absolute values and percentage of total sleep time). Arousal index and wake-time after sleep onset were significantly higher in parasomniac subjects. Sleep fragmentation was mainly concentrated in stages 3 and 4. The slow wave activity (SWA) absolute values averaged during the 2 min immediately preceding an episode of parasomnia were significantly higher than the SWA averaged during 2 min in the same stage 10 min before an episode of parasomnia. Moreover, SWA was higher in the slow wave sleep (SWS) episodes preceding the episode of parasomnia than in the episodes preceding an awakening without an episode of parasomnia. The temporal course of SWA showed a slower exponential decay in both groups, but the time constant of the curve was larger in parasomniacs than in controls. Finally, in control subjects the sleep spindle index increased from the beginning to the end of the night while it was equally distributed in parasomniacs. CONCLUSIONS An abnormal deep sleep associated with a high SWS fragmentation might be responsible for the occurrence of SW or ST episodes.

Insomnia Symptoms in Older Adults: Associated Factors and Gender Differences

OBJECTIVES the aim of this study was to examine the factors associated with insomnia in community-dwelling elderly as a function of the nature and number of insomnia symptoms (IS), e.g., difficulty with initiating sleep (DIS), difficulty with maintaining sleep (DMS), and early morning awakening (EMA). METHODS is were assessed in a sample of 2,673 men and 3,213 women aged 65 years and older. The participants were administered standardized questionnaires regarding the frequency of IS and other sleep characteristics (snoring, nightmares, sleeping medication, and sleepiness) and various sociodemographic, behavioral and clinical variables, and measures of physical and mental health. RESULTS more than 70% of men and women reported at least one IS, DMS being the most prevalent symptom in both men and women. Women reported more frequently two or three IS, whereas men reported more often only one IS. Multivariate regression analyses stratified by gender showed that men and women shared numerous factors associated with IS, sleeping medication, nightmares, sleepiness, chronic diseases, and depression being independently associated with two or three IS. For both sexes, age was associated with only one IS in all age categories. Loud snoring was strongly associated with increased DMS in men only. High body mass index increased the risk for DIS in men but tended to decrease it in women. In women, hormonal replacement therapy, Mediterranean diet, and caffeine and alcohol intake had a protective effect. CONCLUSION our data suggest that women may have specific predisposition factors of multiple IS, which may involve both behavioral and hormonal factors. Identification and treatment of these risk factors may form the basis of an intervention program for reduction of IS in the elderly.

Excessive sleepiness is predictive of cognitive decline in the elderly.

STUDY OBJECTIVES To examine the association of sleep complaints reported at baseline (insomnia complaints and excessive daytime sleepiness (EDS)) and medication, with cognitive decline in community-dwelling elderly. DESIGN An 8-yr longitudinal study. SETTING The French Three-City Study. PARTICIPANTS There were 4,894 patients without dementia recruited from 3 French cities and having a Mini-Mental Status Examination (MMSE) score ≥ 24 points at baseline. MEASUREMENTS AND RESULTS Questionnaires were used to evaluate insomnia complaints (poor sleep quality (SQ), difficulty in initiating sleep (DIS), difficulty in maintaining sleep (DMS), early morning awakening (EMA)), EDS, and sleep medication at baseline. Cognitive decline was defined as a 4-point reduction in MMSE score during follow-up at 2, 4, and 8 yr. Logistic regression models were adjusted for sociodemographic, behavioral, physical, and mental health variables, and apolipoprotein E genotype. EDS independently increased the risk of cognitive decline (odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.02-1.56), especially for those patients who also developed dementia during the follow-up period (OR = 1.39, 95% CI = 1.00-1.97). The number of insomnia complaints and DMS were negatively associated with MMSE cognitive decline (OR = 0.77, 95% CI = 0.60-0.98 for 3-4 complaints, OR = 0.81, 95% CI = 0.68-0.96, respectively). The 3 other components of insomnia (SQ, DIS, EMA) were not significantly associated with MMSE cognitive decline. CONCLUSIONS Our results suggest that EDS may be associated independently with the risk of cognitive decline in the elderly population. Such results could have important public health implications because EDS may be an early marker and potentially reversible risk factor of cognitive decline and onset of dementia.

Excessive Daytime Sleepiness Is an Independent Risk Indicator for Cardiovascular Mortality in Community-Dwelling Elderly. The Three City Study

Background and Purpose— Excessive daytime sleepiness, one of the most frequent sleep complaints in the elderly, may affect survival, but inconsistent results have been observed in that population so far. We therefore estimated the risk of mortality for excessive daytime sleepiness (EDS) in community-dwelling elderly participating in the Three City Study. Methods— The Three City Study is a French population-based multicenter prospective study including 9294 subjects (60% women) aged ≥65 years at recruitment between 1999 to 2001. At baseline, 8269 subjects rated EDS and nocturnal sleep complaints as never, rare, regular, and frequent in response to an administered questionnaire and provided information on medication use for sleep or anxiety. Hazard ratios (HR) of EDS (regular or frequent) for mortality over 6 years were estimated by a Cox proportional hazard model. Results— At baseline, 18.7% of the study participants had regular or frequent EDS. After 6 years of follow-up, 762 subjects had died including 260 from cancer and 196 from cardiovascular disease. EDS was associated with a significant 33% increased risk of mortality (95% CI: 1.13 to 1.61) after adjustment for age, gender, study center, body mass index, previous cardiovascular disease, Mini Mental State Examination score, and cardiovascular risk factors. Further adjustment for current use of medication for sleep and for depressive symptoms slightly diminished the HRs. EDS was equally predictive of mortality in those who snored loudly and in those who did not. EDS was related to cardiovascular mortality but not to mortality attributable to cancer. Conclusion— EDS might be independently associated with total and cardiovascular mortality in community-dwelling elderly.

Hypersomnia associated with mood disorders: A new perspective

Thirty-six subjects affected with hypersomnia associated with mood disorders, 31 with a diagnosis of dysthymia, 4 with a diagnosis of bipolar disorder and one with a diagnosis of major recurrent depression underwent standardized polysomnographic procedures including night 1, MSLT and night 2 (uninterrupted). 36.1% of these subjects had a reduced or intermediate mean sleep latency on the MSLT and 13.8% slept over 9 hr at night. In addition 17 of these subjects underwent prolonged polysomnography during day 2. In comparison with eight subjects affected with idiopathic hypersomnia, mean sleep latency on the MSLT was significantly longer and total sleep time during night 2 and during night 2 plus day 2 was significantly lower in subjects affected with hypersomnia associated with mood disorders. It is concluded that a positive diagnosis of hypersomnia associated with a mood disorder requires both behavioral observation and polysomnography. Among these subjects there may be subjects with well-documented hypersomnia and subjects with anergia facilitating or mimicking sleep.

Effect of cognitive behavioural therapy for insomnia on sleep architecture and sleep EEG power spectra in psychophysiological insomnia

There is now an overwhelming preponderance of evidence that cognitive behavioural therapy for insomnia (CBT‐I) is effective, as effective as sedative hypnotics during acute treatment (4–8 weeks), and is more effective in long term (following treatment). Although the efficacy of CBT‐I in the treatment of chronic insomnia is well known, however there is little objective data on the effects of CBT‐I on sleep architecture and sleep EEG power densities. The present study evaluated, first, subjective change in sleep quality and quantity, and secondly the modifications occurring in polysomnography and EEG power densities during sleep after 8 weeks of CBT‐I. Nine free drug patients with psychophysiological insomnia, aged 33–62 years (mean age 47 ± 9.7 years), seven female and two male participated in the study. Self‐report questionnaires were administered 1 week before and 1 week after CBT‐I, a sleep diary was completed each day 1 week before CBT‐I, during CBT‐I and 1 week after CBT‐I. Subjects underwent two consecutive polysomnographic nights before and after CBT‐I. Spectral analysis was performed the second night following 16 h of controlled wakefulness. After CBT‐I, only scales assessing insomnia were significantly decreased, stages 2, REM sleep and SWS durations were significantly increased. Slow wave activity (SWA) was increased and the SWA decay shortened, beta and sigma activity were reduced. In conclusion CBT‐I improves both subjective and objective sleep quality of sleep. CBT‐I may enhance sleep pressure and improve homeostatic sleep regulation.

Use of modafinil in the treatment of narcolepsy: A long term follow-up study

One hundred and forty patients (104 male and 36 female) aged 42.26 +/- 19.19 (range = 8 to 79.5 years) with narcolepsy-cataplexy were given modafinil (200 to 400 mg) at the Montpellier sleep disorders center from 1984 onwards. The follow-up focused on the reduction of excessive daytime somnolence (EDS), side effects and duration of treatment. In order to determine if any clinical aspect of narcolepsy could be involved in modafinil discontinuation, patients were divided into two groups according to continued or interrupted treatment. When modafinil effect on EDS was evaluated according to a scale varying from 0 (no effect) to 3 (excellent effect), 64.1% of the subjects, scored good or excellent. The mean duration of treatment was 22.05 months +/- 24.9, ranging from 1 to 114 months. Dependency signs were never observed.

Homeostatic process and sleep spindles in patients with sleep-maintenance insomnia (SMI): effect of partial (21 h) sleep deprivation (PSD)

Abstract Objectives : A low level of process S at bedtime would be responsible for a reduced amount of slow-wave activity (SWA) leading to increased alpha activity and awakenings at the end of the night. Methods : Following a base-line night (BLN) recording, 7 sleep-maintenance insomnia subjects (SMI) and 7 sex- and age-matched controls were maintained on 21 h of sleep deprivation. Thereafter, a recovery night (RN) was performed from 2300 h until spontaneous awakening. SWA (power density of the EEG delta band between 0.75 and 4.5 Hz) was monitored by means of spectral analysis (FFT). Sleep spindles and the occupation ratio of Rechtschaffen and Kales EEG bands were observed by integrated digital filtering analysis. Results : SWA was lower in SMI subjects than in controls during RN but was higher than in BLN indicating that the homeostatic process was operating, but weaker in SMI subjects. On the other hand in SMI subjects the sleep spindle index (SSI) did not decrease during slow-wave sleep and was significantly lower than in controls. Moreover during RN the SSI decreased significantly during the first sleep cycle in controls and not in SMI subjects. The existence of an inverse relationship between SWA and SSI was therefore not observed in insomniacs. Finally the mean duration of alpha frequency significantly increased in SMI subjects. Conclusions : It is hypothesised that in SMI subjects, an alteration of the homeostatic process is responsible for insufficient sleep pressure leading to an inability to maintain sleep for an extended period.

Sleep deprivation in narcoleptic subjects: effect on sleep stages and EEG power density.

Sleep of 8 narcoleptic and 8 control subjects was recorded under baseline (i.e., prior wakefulness 16 h) and after 24 h without sleep. During both baseline and recovery total sleep time and stage 2 non-REM sleep were significantly decreased in narcoleptic subjects. Slow wave activity (i.e., EEG power density in the range of 0.75-4.5 Hz) decayed exponentially during baseline and after sleep deprivation in both narcoleptic and control subjects. During both baseline and recovery EEG power density in delta and sigma frequencies in non-REM sleep was enhanced in narcoleptic subjects relative to controls. In REM sleep differences in the same direction were present in delta and beta frequencies. After sleep deprivation EEG power density in non-REM sleep was elevated in delta and some higher frequencies in both patients and controls, but the response to sleep deprivation was stronger in narcoleptic subjects. These data show that in narcoleptic subjects regulatory processes underlying non-REM sleep homeostasis are operative and indicate that the response to sleep deprivation is stronger than in control subjects.

Sleep architecture, slow wave activity and sleep spindles in mild sleep disordered breathing

OBJECTIVE A high degree of sleep fragmentation by arousals related to respiratory events would result in an abnormal distribution of slow wave activity (SWA) and a decrease in sleep spindle density in sleep disordered breathing (SDB) patients when compared to controls. METHODS Eighteen mild SDB subjects (6 females and 12 males), aged 18-56 years with (5<respiratory disturbance index (RDI)<30/h) were compared to 18 controls (11 female and 7 male) aged 18-52 years. The sleep EEG power density was performed using fast Fourier transform (FFT) analysis and sleep spindle density integrated digital filtering analysis (IDFA). Esophageal pressure monitoring was performed on the third night. RESULTS Sleep analysis showed a significant higher number of awakenings <1 min and arousal indexes in total sleep time, in non-REM (NREM) sleep and in slow wave sleep (SWS) than in controls. SWA and theta band decreased significantly from the first to the fourth cycle in both subjects. Theta and sigma bands were significantly lower in patients than in controls, in each sleep cycle and during the whole night. Moreover, the temporal course of SWA showed an exponential decay in both patients and controls but the time constant of the curve was significantly slower in patients than in controls. Furthermore, in both groups, the sleep spindle index was significantly lower in both SWS and stage 2 in patients than in controls. CONCLUSIONS Sleep architecture in mild SDB subjects is characterized by a high degree of sleep fragmentation resulting in a different time course of SWA and a decreased sleep spindle index when compared to controls.