In memoriam: J. Christian Gillin.
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Biomedical subjects
Publications and source records attributed to S Ancoli-Israel.
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STUDY OBJECTIVES: Some, but not all, researchers report that obstructive sleep apnea (OSA) patients experience increased depressive symptoms. Many psychological symptoms of OSA are explained in part by other OSA comorbidities (age, hypertension, body mass). People who use more passive and less active coping report more depressive symptoms. We examined relationships between coping and depressive symptoms in OSA. SETTING: N/A. DESIGN/PARTICIPANTS: 64 OSA (respiratory disturbance index (RDI) > or = 15) patients were studied with polysomnography and completed Ways of Coping (WC), Profile of Mood States (POMS), Center for Epidemiological Studies-Depression (CESD) scales. WC was consolidated into Approach (active) and Avoidance (passive) factors. Data were analyzed using SPSS 9.0 regression with CESD as the dependent variable and WC Approach and Avoidance as the independent variables. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: WC Approach factor (B=-1.105, beta=-.317, p=.009) was negatively correlated and WC Avoidance factor (B=1.353, beta=.376, p=.007) was positively correlated with CESD scores. These factors explained an additional 8% of CESD variance (p<.001) beyond that explained by the covariates: demographic variables, RDI, and fatigue (as measured by the POMS). CONCLUSIONS: More passive and less active coping was associated with more depressive symptoms in OSA patients. The extent of depression experienced by OSA patients may not be due solely to effects of OSA itself. Choice of coping strategies may help determine who will experience more depressive symptoms.
Twenty-four hour circadian activity rhythms and light-exposure levels of 28 older schizophrenia patients (mean age=58years) were examined using an Actillume recorder. Sleep and wake were scored using the algorithm of the ACTION3 software which revealed that the patients slept for 67% of the night and napped for 9% of the day. Patients with more disturbed sleep and less robust circadian rhythms performed more poorly on neuropsychological tests. Patients with higher cognitive functioning and fewer extrapyramidal symptoms were more alert during the day. Few patients were exposed to high levels of illumination during the day, and older age was associated with lower levels of light exposure. Duration of antipsychotic use and higher antipsychotic doses were associated with decreased daytime alertness and less robust circadian activity rhythms. Patients taking antipsychotics were more sleepy both during the day and night than patients not taking antipsychotics. The circadian rhythm disturbances found in these patients did not seem to be due solely to low levels of illumination exposure. Life-style factors, behavioral factors, psychiatric symptoms and medications were likely contributors to the disturbed rhythms. The effects of the sleep disturbances did not seem to be benign. There were strong relationships between sleep and circadian rhythms and functioning.
Sleep disturbances in the elderly may not be a result of the aging process per se, but rather are likely caused by many factors that are amenable to treatment. These factors include medical and psychiatric problems, medications, and circadian rhythm changes, all of which can cause difficulties during sleep at night, and can lead to complaints of insomnia. Other factors that cause disturbances include a high prevalence of specific sleep disorders such as sleep disordered breathing (SDB), periodic limb movements during sleep (PLMS) and rapid eye movement (REM) sleep behavior disorder (RBD). Although these disorders are more prevalent in the older than younger population, they are not exclusive to this age group, and treatment options that are applicable to young adults are also applicable to older adults. On the other hand, dementia and Parkinson's disease are two neurologic disorders that are almost exclusive to the elderly and most often involve sleep disturbances. Because there are many causes of sleep complaints, when considering treatment options one must identify the underlying problem. If caused by illness, effective treatment of a specific medical or psychiatric problem should help alleviate the sleep problem as well. Changes in the timing of drug administration may improve sleep. For the treatment of chronic insomnia, behavior techniques should always be used in combination with pharmacologic therapy, and sedative-hypnotic medications should be considered when appropriate. The treatment of choice for obstructive sleep apnea is continuous positive airway pressure (CPAP). For PLMS, dopaminergic agents are most effective. For RBD, clonazepam effectively controls the aversive sleep behaviors. Sleep disturbances secondary to dementia and Parkinson's disease are usually problematic for the patient as well as the caregiver, whether in the home or in the nursing home. Proper management of these disturbances is beneficial in terms of delaying institutionalization and reducing nursing care costs, as well as improving the quality of life for both patient and caregiver.
BACKGROUND: Obstructive sleep apnea (OSA) is associated with poor sleep quality and a high incidence of nondipping. The aim of this study was to determine the association of sleep quality and nocturnal blood pressure (BP) dipping in an OSA population. METHODS: A total of 44 untreated subjects with mild to severe OSA underwent overnight-attended polysomnography and 24-h ambulatory BP monitoring. Subjects were off antihypertensive medication. The percentage of slow wave sleep, percentage of time awake after sleep onset during the sleep period, sleep efficiency, and arousal index were chosen as measurements of sleep quality. Dipping was evaluated using the change in systolic BP, diastolic BP, and mean arterial pressure. Patients were classified as dippers and nondippers based on a nocturnal drop in mean arterial pressure > 10%. Differences between groups were evaluated by independent sample t tests. Pearson correlation and linear regression were used to evaluate the association of sleep quality and dipping. RESULTS: There were no differences between dippers and nondippers with regard to body mass index, age, or respiratory disturbance index. A total of 84% were nondippers. No difference was found between dippers and nondippers in sleep quality. None of the sleep quality measures correlated with the measurements of dipping. In multiple regression analyses, the percentage of slow wave sleep and arousal index each independently predicted only a small percentage of the variance (approximately 10%) of nocturnal DBP dipping. CONCLUSIONS: The prevalence of nondipping was very high in a population of untreated patients with mild to severe OSA. Nonetheless, sleep quality did not appear to be related to BP dipping.
Sleep disorders and sleeping difficulty are among the most pervasive and poorly-addressed problems of aging. As the population ages, a burgeoning cadre of seniors will seek attention for sleeping difficulties and sleep disorders. Sleep changes with age, and sleeping problems and disorders generally increase with aging. At present, health care professionals are not receiving adequate preparation and training to help the elderly cope with age-related sleeping problems, and several specific areas are ripe for investigation.
OBJECTIVE: The current study was designed to determine whether, with increasing age, sleep apnea improves, becomes worse, or stays the same. BACKGROUND: There is a high prevalence of sleep disordered breathing (SDB) in older adults, but little is known about longitudinal changes. This study followed older adults to examine the natural history of SDB. METHODS: Subjects were randomly selected community-dwelling elderly (n=427). A subset of subjects was studied approximately every 2 years over an 18-year period. Overnight sleep recordings and sleep questionnaires were completed at each time point. RESULTS: Multiple linear regression showed that three variables were associated with change in respiratory disturbance index (RDI):body mass index (BMI) at initial visit (P=0.001), change in BMI (P=0.02), and a consistent self-report of high blood pressure (P=0.005). RDI increase was associated with BMI increase and presence of self-reported high blood pressure. CONCLUSIONS: The changes in RDI that occurred were associated only with changes in BMI and were independent of age. This underscores the importance of managing weight for older adults, particularly those with hypertension.
Fatigue is a major complaint among cancer patients, yet it is unknown whether cancer-related fatigue experienced during the day relates to sleep/wake cycles or to the quality and quantity of sleep obtained at night. Although it is not well defined or well understood at present, cancer-related fatigue is generally regarded as a form of tiredness that does not improve following rest or sleep. Objectively recorded sleep and biological rhythms have not been well investigated in these patients, but it appears that most cancer patients may in fact not be getting a good night's sleep. Evidence is accumulating that sleep is often disturbed in cancer patients, probably owing to a variety of causes. We posit that some degree of cancer-related fatigue experienced during the day may relate to sleep/wake cycles or to the quality and quantity of sleep obtained at night. Different components or dimensions of fatigue (physical, attentional/cognitive, emotional/affective, etc.) are probably associated in some way with disrupted sleep and desynchronized sleep/wake rhythms. These associations may change in measurable ways prior to treatment, during treatment and after treatment completion. In cancer patients, as in other medically ill patients, sleep that is inadequate or unrefreshing may be important not only to the expression of fatigue, but to the patients' quality of life and their tolerance to treatment, and may influence the development of mood disorders and clinical depression. This review summarizes the state of the literature on fatigue, sleep and circadian rhythms.
Many facets of health-related quality of life are diminished in obstructive sleep apnea (OSA) as they are in other chronic medical conditions. We speculated that impairment in health-related quality of life (HRQoL) might result from the fatigue and daytime somnolence associated with the sleep disorder, as an indirect result from the fragmentation of night-time sleep in OSA. Our hypothesis was that sleep fragmentation measures would correlate with poorer HRQoL measured by medical outcomes study (MOS) subscales. Thirty-nine patients with polysomnographically-confirmed OSA participated in this study. Pearson's correlations were performed with the following sleep architecture variables: wake after sleep onset, the total number of brief arousals, the number of respiratory-related arousals, the rate of respiratory events per hour, and total sleep time. To our surprise, although the total number of arousals was associated with health distress (r=-0.481, P < 0.005), it did not correlate with any other subscales indicating poorer physical and mental health. The relatively insensitive measure of total sleep time (TST) correlated in the expected direction with most subscales. However, after controlling for age and gender, respiratory disturbance indices (RDI) and/or number of arousals emerged as significantly associated with mobility, cognitive functioning, social functioning, energy and fatigue, and health distress. Our findings suggest that polysomnographic indicators of sleep quality and sleep continuity may be an important influence determining many aspects of HRQoL in OSA patients.
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.
The mechanism of pathogenesis of hypertension in patients with obstructive sleep apnea (OSA) is unknown. Many investigators point to the high sympathetic nervous system activity (SNS) observed in OSA patients. However, there is no clear explanation as to the mechanism for the development of SNS hyperactivity in these patients. A common feature of patients with OSA is repetitive bouts of transient hypoxemia during sleep. Repetitive transient hypoxemia in rats has resulted in hypertension. In OSA patients, resolution of nocturnal hypoxemia with CPAP has corrected nocturnal and diurnal hypertension. Also, exposure to hyperoxia reduces blood pressure and sympathetic activity in OSA patients, but not in normals. These data suggest a significant role of peripheral chemoreceptors in the regulation of vascular tone. We hypothesize that peripheral chemoreceptors significantly contribute to the pathogenesis of hypertension in patients with OSA and that this is associated with chemoreceptor hyperactivity. This implies that correcting the intermittent nocturnal hypoxemia alone may prevent the cardiovascular morbidity associated with obstructive sleep apnea.
The prevalence of delayed sleep phase syndrome (DSPS) has been estimated to be quite low. Although no genetic inheritance pattern has been described, it has been reported that close to 50% of DSPS patients have biological relatives with similar symptoms. A pedigree of one extended family with symptoms suggestive of DSPS has been identified. Morningness-eveningness questionnaires were administered to all first- and second-degree relatives of a proband identified with DSPS. A total of 51 (86%) questionnaires were returned, and 6 adult biological relatives of 27 (22%) showed a preference for eveningness, which is much higher than reported in the general population. Both the paternal and maternal branches contained affected individuals, suggesting the possibility of a bilineal mode of inheritance. While the trait did not obey simple Mendelian inheritance, the vertical patterns of transmission were consistent with either an autosomal dominant mode of inheritance with incomplete penetrance or a multifactorial mode of inheritance. These data provide some preliminary support to the notion that eveningness, and thus DSPS, may have a genetic component. The prevalence of symptoms suggestive of DSPS is higher in this family than reported in the general population. Case reports such as this support the utility of larger, more systematic studies. It is unclear whether this degree of familiarity is representative of that in the general population.
OBJECTIVE: Obstructive sleep apnea (OSA) is associated with increased prevalence of atherosclerotic disease. A hypercoagulable state thought to underly atherosclerosis has been described in both OSA and systemic hypertension. We wondered about the respective contribution of apnea and hypertension to a hypercoagulable state. DESIGN: Eighty-seven subjects with symptoms suggestive of OSA, mean age 47 years (range 32-64 years), underwent polysomnography and blood pressure (BP) screening. OSA was diagnosed when respiratory disturbance index (RDI) > or = 15. Subjects having systolic BP (SBP) > 140 mmHg and/or diastolic BP (DBP) > 90 mmHg were classified as having hypertension. Three hypercoagulability markers were measured: thrombin/antithrombin III complex (TAT), fibrin D-dimer (DD), and von Willebrand factor antigen (vWF:ag). RESULTS: Analysis of variance and multiple linear regression were performed on the following four subject groups: (1) normotensive non-apneics (n = 19), (2) normotensive apneics (n = 38), (3) hypertensive non-apneics (n = 11), and (4) hypertensive apneics (n = 19). OSA (groups 2 and 4) had no significant main effect on hemostasis. Hypertensives (groups 3 and 4) had higher plasma levels of TAT (median/inter-quartile range, 148/59-188 versus 77/53-108 pmol/l; P = 0.009) and of DD (376/265-721 versus 303/190-490 ng/ml; P = 0.040) than normotensives (groups 1 and 2). Across all subjects, SBP was the only significant predictor of TAT (P = 0.001) and of DD (P = 0.004), whereas DBP was the only significant predictor of vWF:ag (P = 0.029). These findings persisted even after controlling for gender, age, body mass index, RDI, mean SaO2, and hematocrit. CONCLUSION: Hypercoagulability in OSA is mediated by comorbid hypertension and might account for high cardiovascular morbidity in OSA in general.
The Medical Outcomes Study (MOS) inventory is widely used to assess quality of life in chronically ill patients. Although response bias was addressed during its initial validation, we are unaware ofsubsequent studies examining how personality characteristics influence responses on this instrument. We examined the impact of response bias on MOS data reported by 44 obstructive sleep apnea (OSA) outpatients who completed the MOS and Marlowe-Crowne Social Desirability Scale (MC). Social desirability implies responding in a way that the participant believes will be viewed favorably; MC is often used to statistically controlfor this form of response bias on self-report measures. The MOS yielded 2 summary scales (Mental and Physical Health) and 8 dimensions (based on Short Form-36 [SF-36]). Data were analyzed using multiple regression analyses. Results show that there is a significant relation between MC and the Mental and Physical Health factors (R2 = .194, F = 5.069, p = .011) and the eight SF-36 dimensions (R2 = .359, F= 2.448, p = .032). Post hoc analyses did not reveal that any one independent variable was a superior predictor of the MC. Participants scoring high on the MC reported 31% greater health than participants scoring low on the MC. Findings suggest that response bias has a significant influence on MOS data from OSA patients, with the greatest impact on mental health indexes. Controlling for response bias on the MOS and other self-report measures is important in both research and clinical situations with OSA and potentially other chronically ill patients.
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STUDY OBJECTIVES: We studied the effect of continuous positive airway pressure (CPAP) treatment on sympathetic nervous activity in 38 patients with obstructive sleep apnea. DESIGN: Randomized, placebo-controlled trial. SETTING: Patients underwent polysomnography on three occasions in a clinical research center, and had BP monitored over 24 h at home. All of the patients had sleep apnea with a respiratory disturbance index (RDI) > 15. INTERVENTIONS: The patients were randomized blindly to CPAP or placebo (CPAP at ineffective pressure) treatment. MEASUREMENTS AND RESULTS: Prior to therapy, the number of apneas and the severity of nocturnal hypoxia correlated significantly with daytime urinary norepinephrine (NE) levels, but not nighttime urinary NE levels. CPAP treatment lowered daytime BP from 99 +/- 2 mm Hg to 95 +/- 3 mm Hg (mean +/- SEM) and nighttime BP from 93 +/- 3 mm Hg to 88 +/- 3 mm Hg. Placebo CPAP treatment decreased both day and night mean BP only 2 mm Hg. CPAP, but not placebo, treatment lowered daytime plasma NE levels by 23%, daytime urine NE levels by 36%, daytime heart rate by 2.6 beats/min, and increased lymphocyte beta(2)-adrenergic receptor sensitivity (all p < 0.05). The effect of CPAP treatment on nighttime urine NE levels and heart rate did not differ from placebo treatment. There was a suggestion of an effect of placebo CPAP treatment on nighttime measures, but not on daytime measures. CONCLUSION: We conclude that daytime sympathetic nervous activation is greater with more severe sleep apnea. CPAP treatment diminished the daytime sympathetic activation; the potential nighttime effect of CPAP treatment was obscured by a small placebo effect.
BACKGROUND: It is commonly believed that sleep duration in the population has been declining gradually. Whereas sleep restriction in the laboratory induces sleepiness and mood disturbances, it is not certain whether a short sleep duration impairs the quality of everyday life. METHODS: Using population-based data, we explored whether greater habitual sleep duration is a predictor of better health-related quality of life, measured by the Quality of Well-Being (QWB) scale. The relationships between QWB and several potential correlates were examined in a stepwise linear regression analysis. RESULTS: Neither subjective nor actigraphic sleep duration were associated with QWB. Greater quality of well-being was associated with greater sleep satisfaction, younger age, less obesity, non-Hispanic White ethnicity, and greater experienced illumination. CONCLUSION: These data suggest that increasing sleep duration may not directly improve quality of life, despite evidence that curtailment of nocturnal sleep is associated with fatigue.
BACKGROUND: Compared with normal subjects, depressed patients have shorter rapid eye movement sleep latency (REML), increased REM and decreased slow wave sleep as a percentage of total sleep time (REM%, SWS%), and longer sleep latency (SL). Obstructive sleep apnea (OSA) patients experience longer REML, decreased REM% and SWS%, and shorter SL. We examined the interplay of depressive symptoms, OSA, and sleep architecture. METHODS: Subjects (n = 106) were studied with polysomnography. OSA was defined as a Respiratory Disturbance Index > or = 15. Subjects were divided into Hi/Lo groups using a Center for Epidemiological Studies-Depression (CES-D) score of 16. RESULTS: OSA patients had shorter SL than non-OSA patients (14.5 vs. 26.8 min, p <.001); Hi CES-D subjects showed a trend toward longer SL than Lo CES-D subjects (23.7 vs. 17.5 min, p =.079). Significant OSA x CES-D interactions emerged, however, for REM% (p =.040) and SL (p =.002): OSA/Hi CES-D subjects had higher REM% than OSA/Lo CES-D subjects (19.3% vs. 14.3%, p =.021); non-OSA/Hi CES-D subjects had SL (35.3 min) 2-3 times as long as other subjects (p =.002-.012). CONCLUSIONS: Because of the high prevalence of OSA and depression, findings suggest that OSA must be considered in studies of mood and sleep architecture. Conversely, depressive symptoms must be considered in studies of OSA and sleep architecture.