Electroencephalographic sleep profiles during depression. Effects of episode duration and other clinical and psychosocial factors in older adults.

BACKGROUND: Limited evidence suggests that polysomnographic alterations may be more prominent early in a depressive episode. Whether the effects of episode duration extend beyond middle age and appear in late-life depression as well has important implications for treatment decisions and for understanding depressive illness across the life span. Furthermore, the impact of episode duration on sleep has not been examined in the context of other factors related to clinical history and psychosocial status. METHODS: Eighty-three persons aged 60 years or older with recurrent depression were studied: 34 had been depressed for 2 to 16 weeks and 49 for longer periods. An age- and gender-matched group of 48 persons with no history of major depression served as controls. Initial univariate analyses examined duration effects on electroencephalographic (EEG) sleep measurements. Multivariate analyses considered the combined effects of episode duration, clinical variables, and psychosocial variables on EEG sleep profile. RESULTS: Episode duration was strongly associated with sleep continuity, architecture, and rapid eye movement: subjects who were earlier in their depressive episodes had their sleep impaired more than those later in their episodes, who, in turn, were more impaired than controls. Moreover, clinical characteristics of subjects' depressive illness, demographic variables, and psychosocial stressors and supports had unique effects on the EEG sleep profile. CONCLUSION: Episode duration appears to be a potent factor to consider when evaluating sleep during depression. The additional contribution of clinical and psychosocial characteristics to the prediction of the EEG sleep profile demonstrates the importance of incorporating these variables into models of the psychobiologic characteristics of depression. The results are relevant to the timing and focus of therapeutic interventions.

Sleep deprivation as a probe in the elderly.

Decreased slow-wave sleep (SWS) and sleep continuity are major effects of healthy aging and of associated psychopathological states. Using sleep deprivation, we studied the extent to which age- and psychopathology-related sleep "decay" is reversible in aged normal, depressed, and demented subjects. Depression or probable Alzheimer's dementia compromised the augmentation of sleep continuity and SWS seen in healthy elderly following sleep deprivation. Rapid eye movement (REM) latency decreased during recovery sleep in the controls but increased in both patient groups. Compared with demented patients, depressed elderly had greater severity of sleep continuity disturbance both before and after sleep deprivation, a more protracted course of recovery sleep, and increased slow-wave density in the second non-REM (NREM) sleep period (during recovery). The REM sleep time was diminished in dementia compared with depression both at baseline and during recovery sleep. These differential effects of age, health, and neuropsychiatric disease on recovery from sleep loss are relevant to recovery or reversal theories of sleep and have implications for daytime well-being in the elderly.

Electroencephalographic sleep in depressive pseudodementia.

Twenty-six patients with mixed symptoms of depression and cognitive impairment were studied with serial clinical ratings and sleep electroencephalograms during a one-night sleep-deprivation procedure. A subgroup of these patients with depressive pseudodementia (n = 8) had less severe symptoms of dementia at baseline and showed significant improvements in both Hamilton Depression Rating Scale scores and Profile of Mood States tension scores following sleep deprivation, while another subgroup of patients having primary degenerative dementia with depression (n = 18) showed no change or worsening in Hamilton depression and Profile of Mood States tension ratings. Baseline sleep measures demonstrated significantly higher rapid eye movement (REM) percent and phasic REM activity/intensity in pseudodemented compared with demented patients. While both groups had increases in sleep efficiency, sleep maintenance, and slow-wave sleep following sleep deprivation, recovery night 2 was characterized by greater first REM period duration in depressive pseudodementia than in dementia. These differences in REM sleep rebound (using an REM period 1 cutoff of greater than or equal to 25 minutes) permitted correct identification of 88.5% of patients. Implications of these data for current theories regarding sleep, aging, and psychopathology are discussed.

Reliable discrimination of elderly depressed and demented patients by electroencephalographic sleep data.

Using electroencephalographic sleep data from a sample of 235 elderly subjects, discriminant function analyses of sleep alterations in depression and dementia were performed. Overall, 80% of patients were correctly classified using a backward discriminant function analysis, and 81% with a general stepwise discriminant function analysis. Four measures contributed to the separation of depressed and demented patients: rapid eye movement (REM) sleep latency (lower in depressives); REM sleep percent (higher in depressives); indeterminate non-REM sleep percent (higher in demented patients, reflecting greater loss of spindles and K complexes); and early morning awakening (more marked in depressives). When both discriminant functions were subjected to cross-validation in independent subsamples, both procedures correctly identified 78% of patients. The classification functions derived from nondemented depressed and nondepressed demented patients were applied to a mixed-symptom group (n = 42). Overall, 27 patients (64%) with either depressive pseudodementia or dementia with depressive features were correctly classified using the same four predictor variables. These findings suggest that sleep physiological alterations of depression and dementia reflect between-group differences in sleep continuity, sleep architecture, and REM sleep temporal distribution, and that the differences are statistically reliable, in both diagnostically pure and mixed clinical presentations. These findings are discussed in the context of current hypotheses of sleep regulation and its mechanisms.

Rapid eye movement sleep deprivation as a probe in elderly subjects.

The effects of a 2-night rapid eye movement (REM) sleep deprivation (RSD) procedure on electroencephalographic sleep and mood were examined in 15 healthy elderly control subjects, 14 elderly patients with endogenous depression, and 15 patients with primary degenerative dementia. Compared with control subjects, both patient groups maintained a higher amount of REM sleep time and REM activity during RSD. Unexpectedly, depressed patients showed little rebound in visually scored or automated REM sleep measures following RSD, and they showed stability of REM activity temporal distribution from baseline to recovery conditions. This contrasted with the rebound in REM sleep activity seen in control subjects, and the more modest increase in demented patients. The RSD was fairly specific, with some impact on delta sleep during the procedure but not during recovery sleep. Mood ratings were unaffected by RSD. These findings demonstrated a greater plasticity of REM sleep regulation in the healthy elderly control subjects and suggested a higher REM "pressure" with a "ceiling effect" in depressed patients. Patients with dementia appeared to have an impaired capacity to respond to the challenge of RSD.

Sleep after spousal bereavement: a study of recovery from stress.

AIM: In this study, we compared repeated measures of electroencephalographic (EEG) sleep and subjective sleep quality in nondepressed, spousally bereaved elders and a healthy control group, in order to search for possible psychobiological correlates of bereavement not confounded by concurrent major depression. METHOD: Laboratory-based EEG sleep studies and measures of subjective sleep quality (Pittsburgh Sleep Quality Index [PSQI]) were repeated at 3, 6, 11, 18, and 23 months after spousal bereavement in a study group of 27 elderly volunteers. Data were compared with similar measures from a control group of 27 nonbereaved subjects recorded on three occasions 1 year apart. Repeated-measures analysis of variance (ANOVA), using age as a covariate, examined effects due to time on selected variables in the bereaved group, as well as effects due to group, time, and group-by-time interactions in the experimental and control subjects. RESULTS: Bereaved and control groups showed consistent differences over time in the phasic measures of rapid eye movement (REM) sleep (higher in bereaved subjects during the first and third REM sleep periods), but were similar on all other EEG sleep measures over the 2 years of observation. The bereaved showed a small decline in the percentage of slow-wave sleep over 2 years, but measures of sleep efficiency, REM latency, and delta sleep ratio were stable and did not differ from values seen in control subjects. Bereaved and control subjects were also similar on subjective sleep quality. CONCLUSION: During successful adaptation to the loss of a spouse, and in the absence of major depression, spousal bereavement is associated with elevation in the phasic measures of REM sleep but does not appear to be associated with other physiologic sleep changes typical of major depression when studied at 3 to 23 months after the event. Although this observation does not preclude the possibility of significant sleep disturbance nearer the time of the event, it suggests that preservation of normal sleep following a major negative life event may be an important correlate of the resilience seen in successful aging. The elevation in REM density may provide a psychobiological correlate of bereavement not confounded by concurrent major depression.

Electroencephalographic sleep in spousal bereavement and bereavement-related depression of late life.

Although spousal bereavement in late life is common and frequently leads to major depression, the boundary between bereavement without a depressive syndrome and bereavement-related depression has been insufficiently studied from a physiological perspective. Because other forms of depression are associated with physiological changes, including sleep, we have attempted to clarify the relationship of bereavement and bereavement-related depression by investigating electroencephalographic (EEG) sleep in 31 elderly volunteers with recent spousal bereavement, stratified by the presence (n = 15) or the absence (n = 16) of major depression (Research Diagnostic Criteria). Entry into the study was limited to volunteers without a personal history of psychiatric disorder. As hypothesized, bereaved subjects with major depression had significantly lower sleep efficiency, more early morning awakening, shorter rapid eye movement (REM) latency, greater REM sleep percent, and lower rates of delta wave generation in the first nonREM (NREM) period, compared with bereaved subjects without depression. Furthermore, the sleep of bereaved subjects with single-episode major depression resembled that of elderly patients with recurrent unipolar major depression (n = 15) on measures noted above. Sleep in bereavement without depression was similar to that of 15 healthy control subjects (neither bereaved nor depressed). These findings suggest that the current DSM-III-R concept of uncomplicated bereavement is not confirmed, as the sleep patterns of subjects who develop a depressive syndrome in the context of bereavement, many of whom might be considered to have "uncomplicated bereavement" by DSM-III-R standards, are identical to sleep patterns found in major depressive episodes. To our knowledge, this is the first study of EEG sleep in spousal bereavement with and without major depression.

Maintenance nortriptyline effects on electroencephalographic sleep in elderly patients with recurrent major depression: double-blind, placebo- and plasma-level-controlled evaluation.

Our aim was to contrast the effects of maintenance nortriptyline and placebo on electroencephalographic sleep measures in elderly recurrent depressives who survived 1-year without recurrence of depression. Patients on nortriptyline took longer to fall asleep and did not maintain sleep better than patients on placebo; however, maintenance nortriptyline was associated with more delta-wave production and higher delta-wave density in the first non-REM (NREM) period relative to the second. Nortriptyline levels were positively but weakly related to all-night delta-wave production during maintenance (accounting for 6.6% of the variance in delta-wave counts). Total phasic REM activity increased 100% under chronic nortriptyline relative to placebo, with a robust increase in the rate of REM activity generation across the night. Effective long-term pharmacotherapy of recurrent major depression is associated with enhancement in the rate of delta-wave production in the first NREM period (i.e., delta sleep ratio) and of REM activity throughout the night.

Sleep, gender, and depression: an analysis of gender effects on the electroencephalographic sleep of 302 depressed outpatients.

Gender-related differences in electroencephalographic (EEG) sleep were examined in 151 pairs of men and women with major depression, all outpatients, matched for age and severity of depression. Across five decades (age 21-69), depressed men had less slow-wave sleep than did depressed women. Gender differences were small with respect to visually scored measures of slow-wave sleep time and percent, but moderate for gender differences in automated measures of slow-wave density. The time constant of the polygraph preamplifier significantly affected both visually scored and automatically scored slow-wave sleep. Other measures such as REM sleep latency, first REM period duration, sleep efficiency, and early morning awakening, showed robust age effects, but no main effects for gender or gender-by-age interactions. Gender effects on slow-wave sleep and delta-wave counts in depression parallel gender effects seen in healthy aging. The possibility of occult alcohol use by depressed male outpatients cannot be definitely excluded as a partial explanation of the current findings. However, covarying for past alcohol abuse did not negate the statistical significance of the observed gender effects on slow-wave sleep and delta-wave density. The possibility of gender differences in slow-wave regulatory mechanisms is suggested, but similarity in temporal distribution of delta-wave density between the first and second non-rapid-eye-movement (NREM) periods does not support gender differences in slow-wave sleep regulation.

Sleep in the wake of complicated grief symptoms: an exploratory study.

Our aim was to explore the concept that the symptoms of complicated grief may be a form of posttraumatic distress, rather than depression, and thus may have different effects on sleep. Sixty-five recently bereaved elders with varying levels of symptoms of complicated grief and depression were stratified by high versus low levels of symptoms; a two-way analysis of variance examined main effects of level of complicated grief symptoms and depressive symptoms on selected sleep measures, as well as interactions. Complicated grief symptoms were independently associated with mild subjective sleep impairment but showed no main effects on electroencephalographic (EEG) sleep measures. In a multiple regression analysis, complicated grief symptoms interacted with depressive symptoms to increase REM sleep percent. Thus, it appears that complicated grief symptoms do not entail the changes of EEG sleep physiology seen in depression, with the possible exception of an interaction with coexisting depression to enhance REM sleep percent.

EEG sleep in elderly depressed, demented, and healthy subjects.

In a prospective study of EEG sleep patterns in 25 elderly depressives, 25 elderly demented patients, and 25 healthy, elderly control subjects, the sleep of depressives was characterized by reduced REM sleep latency, increased REM percent and first REM period density, and altered temporal distribution of REM sleep, as well as by diminished sleep maintenance (correlated significantly with Hamilton ratings of depression: multiple R = -0.42, p less than 0.05). In contrast, the sleep of demented patients showed reduced REM sleep percent, but normal REM temporal distribution, increased loss of spindles and K-complexes (the latter correlating significantly with severity of cognitive impairment as measured by the Folstein score: multiple R = -0.59, p less than 0.01), and less severe sleep maintenance difficulty than for depressives. An examination of REM latency demonstrated a skewed distribution in depression (i.e., 42% of nights with sleep-onset REM periods), but a normal distribution in the controls and demented subjects. A REM latency cut-off score of 30 min correctly classified 68% of all patients (kappa = 0.36; p less than 0.005), compared with 78% correctly identified in our retrospective study (Reynolds et al. 1983).

Daytime sleepiness and performance among healthy 80 and 20 year olds.

This study investigated the relationship of daytime sleepiness and performance on a vigilance test in a sample of 10 healthy men and 13 women in their 80s (mean age 83.0 +/- 3.1 years) and 18 men and 12 women in their 20s (25.0 +/- 3.1). We hypothesized that "successfully" aged healthy individuals would have more daytime sleepiness with differentially greater decrements in performance than a younger comparison group. Daytime sleepiness was measured physiologically by the Multiple Sleep Latency Test (MSLT) and through self-report by the Stanford Sleepiness Scale (SSS). Morning and evening performance was measured with the Mackworth Clock Test of vigilance. The major findings were the absence of correlation between either MSLT or SSS daytime sleepiness with performance measures, no difference in daytime sleepiness between the old and young groups and performance decrements among the healthy elderly on all parameters. Results suggest that the modest decrements in performance among the elderly cannot be attributed to daytime sleepiness.

Sleep-disordered breathing in healthy and spousally bereaved elderly: a one-year follow-up study.

This study examined the progression of sleep-disordered breathing (SDB) over 1 year in two samples of elderly subjects: 45 healthy controls (20 men; 25 women mean age 74.8 years) and 27 recently spousally bereaved elders (9 men; 18 women, mean age 69.7 years). Although controls and bereaved subjects did not differ in the proportions with SDB, both groups showed a rise in the proportion of subjects with apnea hypopnea index > or = 5 and > or = 10 at 1-year follow-up and a small but statistically significant worsening in average maximum desaturation. The severity of SDB did not correlate with medical burden or with other clinical variables, such as severity of depressive symptoms. In summary, SDB increased longitudinally in both samples. This finding may have health implications for the aging population although at this time the implications are unclear.

Bedside differentiation of depressive pseudodementia from dementia.

The authors analyzed the pretreatment clinical presentations of 14 patients with depressive pseudodementia and 28 patients with primary degenerative dementia as measured by the Mini-Mental State, the Blessed Dementia Rating Scale, and the Hamilton Rating Scale for Depression. They found that patients with pseudodementia showed significantly greater pretreatment early morning awakening, higher ratings of psychological anxiety, and more severe impairment of libido. Patients with dementia, however, showed significantly more disorientation to time, greater difficulty finding their way about familiar streets or indoors, and more impairment with dressing. The authors suggest that these findings be considered preliminary.

Electroencephalographic sleep in recently remitted, elderly depressed patients in double-blind placebo-maintenance therapy.

The aim of this double-blind placebo-controlled study was to assess the effects of clinical state on electroencephalographic (EEG) sleep measures in elderly patients with recurrent major depression. We hypothesized that rapid-eye movement (REM) latency and delta sleep ratio would remain stable between actively depressed and remitted states (i.e., show state independence), and measures of sleep continuity would improve with remission (i.e., show state dependence). Fifteen elderly outpatients (mean age 65.3 years) had sleep evaluations while ill and after remission, an average of 38 weeks later. All patients were in a double-blind placebo-maintenance condition at the time of follow-up studies. The major findings were: 1) no significant change in either REM latency or delta sleep ratio; 2) reduction in early morning awakening; and 3) improvement in subjective sleep quality despite the stability of most polysomnographic measures. We conclude that REM latency and delta sleep ratio are state-independent in patients with late-life depression, and that early morning awakening and sleep quality improve with remission of symptoms. These findings suggest that EEG sleep changes may have significance for understanding the longitudinal course of depression in late life.

Longitudinal effects of nortriptyline on EEG sleep and the likelihood of recurrence in elderly depressed patients.

Our objectives were to determine the effects of nortriptyline and placebo on subjective and EEG sleep measures over 1 year of maintenance therapy in elderly depressed patients and to determine the relationship of such effects to recurrence in nortriptyline or placebo-treated patients during maintenance therapy. EEG and subjective sleep assessments were conducted before and during a maintenance therapy study of patients suffering from major depression. During acute treatment all patients received nortriptyline plus interpersonal psychotherapy (IPT). During maintenance treatment patients were randomly assigned to double-blind treatment in one of four cells: nortriptyline with IPT; nortriptyline with medication clinic (no IPT); placebo with IPT; or placebo with medication clinic. Sleep evaluations were conducted at one point before treatment, one point following remission during continuation nortriptyline/IPT treatment, and at three time points after random assignment to maintenance treatment. The setting was the sleep laboratory of the outpatient depression treatment clinic, and subjects were a convenience sample of media-recruited and clinically referred elderly outpatient depressed patients (n = 72). Complete sleep analyses were conducted for 21 nortriptyline- and 10 placebo-treated patients throughout 1 year of maintenance treatment. The main outcome measures were subjective and EEG sleep measures and the recurrence of major depression. Our results show that nortriptyline acutely and persistently decreased REM sleep, increased phasic REM activity, decreased sleep apnea, and had no effect on periodic limb movements during sleep. Recurrence on maintenance nortriptyline was associated with lower phasic REM activity during early continuation therapy, but EEG sleep measures did not predict recurrence during placebo maintenance therapy. Patients treated with nortriptyline had a lower recurrence rate than those treated with placebo. Better subjective sleep quality and maintenance IPT were associated with a lower rate of recurrence regardless of nortriptyline treatment. It seems that nortriptyline has persistent effects on REM sleep and sleep apnea in elderly depressed patients. Maintenance nortriptyline, maintenance IPT, good subjective sleep quality, and high-phasic REM activity are associated with a reduced likelihood of the recurrence of depression during maintenance therapy.

Sleep in late-life recurrent depression. Changes during early continuation therapy with nortriptyline.

The sleep of thirty elderly patients with recurrent unipolar depression was examined at baseline (before acute treatment of the index episode) and again in a state of symptomatic remission with nortriptyline (mean steady-state level: 82.1 ng/ml). Continuation therapy with nortriptyline was associated with improvement of polysomnographic sleep maintenance (mainly in the third and fourth sleep cycles, to a level similar to that of controls), prolongation of rapid-eye-movement (REM) sleep latency (exceeding that of controls), and potentiation of slow-wave activity during the first non-REM (NREM) sleep period. Clinical improvement, as measured by the Hamilton Depression Rating Scale, was significantly associated with shift of delta activity toward sleep onset (p less than 0.002), prolongation of REM sleep latency (p less than 0.0001), and improvement in sleep maintenance (p less than 0.0002). Multiple regression analysis showed that the single best correlate of clinical change was prolongation of REM sleep latency (i.e., prolongation of first NREM period). Perceived sleep quality improved significantly during early continuation therapy with nortriptyline, but not to the level reported by a group of 30 age- and sex-matched healthy controls. The findings are consistent with the concept that anti-depressant drug efficacy may depend upon strengthening of the homeostatic regulation of sleep and upon changes in the REM-sleep regulation.

Stability of EEG sleep and sleep quality in healthy seniors.

When the electroencephalogram-recorded (EEG) sleep of 19 healthy seniors (9 men, 10 women) aged 60-82 years was restudied after an average interval of 2.2 years, most measures of EEG sleep and sleep quality were stable over time. Both elderly men and women showed more awakenings during the second recording series, but no change in visual or computer-scored delta activity. Furthermore, gender-dependent sleep changes were noted only in phasic rapid eye movement (REM) measures (increasing in men, decreasing in women). Reports of sleep quality were also stable over time despite the increase in awakenings, with women reporting a lower sleep quality than men.

A longitudinal study of laboratory- and diary-based sleep measures in healthy "old old" and "young old" volunteers.

The major aim of this study was to examine laboratory- and diary-based measures of sleep in a group of healthy ("successfully aging") "old old" subjects (> or = 75 years of age), as contrasted with a group of "young old" subjects (60-74 years of age), who were followed longitudinally for 2 years. We hypothesized that sleep would deteriorate to a greater extent over time among the old old subjects than among the young old. The study group consisted of 50 elders (21 male, 29 female; 23 old old, 27 young old), each studied at baseline and then again at 1- and 2-year follow-up. Analysis of variance was used to determine main effects of age group, gender and time on key sleep measures. Most measures were found to be remarkably stable over time. However, some decay was detected in sleep efficiency among the old old, but not among the young old. In a multiple regression model for the cohort as a whole, age, cognitive status and medical burden at baseline predicted subsequent declines in sleep efficiency over the 2-year period. To our knowledge, this is the first longitudinal data set on sleep in the healthy old old.

Quantification of subjective sleep quality in healthy elderly men and women using the Pittsburgh Sleep Quality Index (PSQI)

Subjective sleep quality deteriorates with aging, but the extent to which this is a product of age itself, as opposed to the medical or psychiatric problems associated with aging, has not been carefully studied. To investigate this issue, we examined the subjective sleep quality of 44 healthy subjects over 80 years of age (20 men, 24 women), and 35 healthy subjects [corrected] between the ages of 20 and 30 (23 men, 12 women) using the Pittsburgh Sleep Quality Index (PSQI). All subjects underwent rigorous medical and psychiatric evaluations to verify that they were in excellent physical and psychological health. Significant age effects were noted for the global PSQI score and several PSQI component scores, but overall sleep quality for the majority (68.1%) of 80-yr-olds fell within a categorically defined range for "good" sleepers. Measures of habitual sleep quality did not correlate strongly with most polysomnographic sleep measures, number of medications used or circadian measures in elderly subjects. These results show that subjective sleep quality does deteriorate in the healthy elderly, but not to the level seen in patients with sleep disorders. Extremely healthy elderly subjects appear to adapt in their perception of objectively disturbed sleep.