Karen E. Moe

Sleep complaints cosegregate with illness in older adults Clinical research informed by and informing epidemiological studies of sleep

OBJECTIVE The more recent epidemiological studies of sleep complaints have shown that when factors such as physical and psychiatric illness, medication use and drug and alcohol use are accounted for, the age-related increase in prevalence of sleep complaints is strikingly less than in those earlier studies without such controls. In an effort to support this finding, we examined the relationships between clinical health screenings and sleep complaints and disorders in two large groups of potential research volunteers (total N=2954). METHODS As part of a study of older adults at risk for Alzheimers disease, two large groups of potential research volunteers (n=1619 and 1335, respectively) replied to advertisements that made no mention of sleep and underwent three increasingly rigorous levels of health screening. At each level of screening, medical and psychiatric health and history were assessed and, where appropriate, subjects were excluded from further study participation before any mention of sleep quality or sleep complaint was made. The remaining subjects then underwent polysomnography. RESULTS Of 1619 elderly adult volunteers screened in this manner, only 51 (3.14%) were found to have significant sleep complaints or disorders. The second group of 1335 screened in this manner revealed a similar pattern with only 18 (1.35%) having significant sleep complaints or disorders. CONCLUSIONS These findings indicate that careful health assessments will screen out most sleep complaints and disorders in the older population and lend further support to the epidemiological evidence demonstrating that the bulk of geriatric sleep complaints and disorders is not the result of age per se, but rather cosegregates with medical and psychiatric disorders and related health burdens.

Sleep/wake patterns In Alzheimer's disease: relationships with cognition and function

SUMMARY  Alzheimers disease (AD), the most common dementing disorder of aging, is a progressive neurodegenerative disease of unknown etiology. Two of the common clinical features of AD are progressive cognitive and functional impairment, and disturbed sleep/wake patterns. We examined sleep/wake patterns and cognitive and functional status measures in a large sample of AD subjects ranging from mild to moderate‐severe in impairment. All subjects survived at least 2 years after initial diagnosis. Regression analyses revealed that sleep/wake variables were highly correlated with and explained significant variance in cognitive and functional measures. More wakefulness during the night and longer REM latencies were associated with impaired cognition and function while more REM and slow‐wave sleep were associated with preserved cognition and function. These results indicate that with advancing severity of the disease, sleep/wake patterns are disrupted in parallel with the disturbances in cognition and function that are the hallmarks of AD. Further, they suggest that the neural substrates underlying each process degenerate at somewhat comparable rates.

Healthy Elderly Women and Men Have Different Entrained Circadian Temperature Rhythms

Body core temperature was measured in healthy elderly men and women under entrained conditions. Female subjects showed a larger amplitude and a higher peak temperature than male subjects. In addition, acrophase was advanced for females by an average of 49 minutes. Variability in acrophase was greater for males than females. This pattern of gender differences varies considerably from the pattern others have observed in young subjects, suggesting that aging may affect the circadian timing system of males and females differently.

Growth hormone releasing hormone improves the cognition of healthy older adults

Declines in the activity of the somatotrophic axis have been implicated in the age-related changes observed in a number of physiological functions, including cognition. Such age-related changes may be arrested or partially reversed by hormonal supplementation. We examined the effect of 6 months treatment with daily growth hormone releasing hormone (GHRH) or placebo on the cognition of a group of 89 healthy older (68.0+/-0.7) adults. GHRH resulted in improved performance on WAIS-R performance IQ (p<0.01), WAIS-R picture arrangement (p<0.01), finding As (p<0.01), verbal sets (p<0.01) and single-dual task (p<0.04). GHRH-based improvements were independent of gender, estrogen status or baseline cognitive capacity. These results demonstrate that the age-related decline in the somatotrophic axis may be related to age-related decline in cognition. Further they indicate that supplementation of this neuro-hormonal axis may partially ameliorate such cognitive declines in healthy normal older adults and potentially in individuals with impaired cognitive function (i.e., mild cognitive impairment and Alzheimers disease).

Urinary free cortisol and sleep under baseline and stressed conditions in healthy senior women: effects of estrogen replacement therapy

The purpose of this study was to examine the effects of a mild 24‐h stress (indwelling IV catheter) on cortisol and sleep in postmenopausal women, and to evaluate differences due to estrogen replacement therapy (ERT) status. This study, conducted in the General Clinical Research Center at the University of Washington Medical Center, examined sleep, cortisol and sleep‐cortisol relationships in both baseline and stress conditions, and compared women on ERT with women not on ERT. Forty‐two women (age=69.6 ± 6.2 years [SD]), of whom 20 were on ERT, participated. Urinary free cortisol (UFC) levels and sleep polysomnography were measured over both 24‐baseline and stress condition. Sleep was impaired in the stress condition for both groups; mean UFC levels were higher, sleep efficiency and minutes of stages 2, 3 and 4 sleep were reduced, and morning risetime was earlier in the stress than baseline condition. For the combined groups, age‐controlled correlations between 24‐h UFC and sleep were significant in both conditions: at baseline, UFC levels were associated with earlier time of rising and less REM sleep, and under stress with reduced sleep efficiency, there was reduced minutes of stages 2, 3, 4 sleep, reduced REM sleep, and an earlier risetime. The pattern of negative significant correlations between UFC and sleep/sleep timing remained when plasma estrogen was statistically controlled; however, when groups were examined separately, the significant negative UFC‐sleep relationships were confined to the non ERT group. Elevated 24‐h UFC is associated with impaired sleep and earlier awakening in older women not on ERT, but not in women on ERT.

Age trends in the sleep EEG of healthy older men and women.

SUMMARY  The all‐night sleep EEGs of 314 (191 women, 123 men) healthy older subjects between the ages of 45 and 90 were studied for age trends in the power spectra of the all‐night NREM sleep EEG. Power spectra of the unnormalized EEG of the women show a power loss in the delta band and a power increase in the beta band with increasing age. For the men no significant trends in the power spectra of the unnormalized EEG were in evidence. A normalization of the power spectra was performed by referencing each logarithmically expressed spectra to its area between 2 Hz and 30 Hz. For both genders the normalized spectra show significant decreases in power at many frequencies below 16 Hz and significant increases in power at frequencies above 18 Hz with increasing age. The age trends observed in the spectra of this population (45‐90y age group) are about a third of the magnitude of those reported in the literature for subjects between the ages of 20y and 40y.

Major unipolar depression and mild Alzheimer's disease: differentiation by quantitative tonic REM EEG☆

In a previous report, tonic REM sleep epochs from the all-night sleep EEG were processed and analyzed to produce a diagnostic that discriminated mild Alzheimers disease (AD) from cognitively unimpaired control subjects. Here, we examine the specificity of this diagnostic in distinguishing depression from AD. Twenty-four cognitively unimpaired seniors (aged 63 +/- 1.3) with major depressive disorder (unipolar) were monitored for all-night EEG in a manner identical to that used in our previous report. Tonic REM EEG epochs were preconditioned, spectrally analyzed and compared with known populations of control and AD EEG spectra. Instances when a given depressed subjects spectra fell within spectral zones unique to control or AD populations formed a diagnostic score (control, AD, neither of these). Diagnostic scores correctly identified 88% (21/24) of cognitively unimpaired seniors with major depressive disorder (unipolar). This can be compared with 89% (31/35) of mild AD subjects and 100% (43/43) of control subjects correctly identified in our previous report. This diagnostic also correctly classified as to eventual clinical AD/not AD outcome 8 subjects with both major depressive disorder and validated memory complaints. The diagnostic discrimination of AD is based on the fact that AD subjects have significantly less tonic REM EEG energy in the 13-30 Hz frequency range and more in the 1-10 Hz range than control or depressed subjects, as shown in conventional spectral analysis.

Entrained body temperature rhythms are similar in mild Alzheimer's disease, geriatric onset depression, and normal aging

Sleep-wake rhythms are known to be altered in Alzheimers disease (AD) and in unipolar depression. Other evidence suggests that the circadian rhythm in body temperature may be altered as well. Entrained circadlan temperature rhythms were measured in healthy elderly men and women, as well as in men and women suffering from unipolar depression or mild AD, to examine this possibility. There were no differences in the temperature rhythm characteristics of subjects with depression or AD compared with healthy control subjects. However, gender differences were observed. Female control subjects showed a larger amplitude, higher peak temperature, and earlier acrophase relative to male control subjects. Also, the mesor of female AD subjects was higher than for male AD subjects. These results are discussed in the context of the widely varying subject populations used in other studies. Geriatr Psychiatry Neurol 1992;5:65–71).

Quantitative analysis of the EEG during tonic REM sleep — methodology

Frequency and amplitude characteristics of the clinical (waking) electroencephalogram (EEG) can be diagnostically useful in neuronal degenerative disorders such as Alzheimers or other cortical dementias. However, interpretation of the clinical EEG may be limited by many factors, including movement and muscle artifacts and uncontrolled variations along the alert/drowsy continuum. Moreover, the clinical EEG involves subjective judgement by experts whose opinions often differ. In an effort to address these problems, we have developed a computer-automated technology that examines the digitized, all-night sleep EEG for frequency and amplitude characteristics of potential diagnostic relevance to Alzheimers dementia. Robust time series analysis techniques and a modified power spectral analysis (Z-spectra) are used to suppress artifactual information and to automatically select samples of tonic REM sleep EEG. The spectra (amplitude vs. frequency relationship) of this specific EEG state is then assessed for diagnostically relevant information.

Growth Hormone Releasing Hormone Treatment in Normal Aging

Because the aging pituitary remains responsive to stimulation by growth hormone (GH) secretagogues - GHRH, ghrelin, and their mimetics - these compounds could potentially be used instead of GH itse...