Sleep disorders and sleep medicine in demented patients

Demented elderly people often show severely fragmented sleep-waking patterns and are associated with disorganized circadian rhythm. Frequent nocturnal awakening and associated behavioral and psychological symptoms in demented people place a heavy burden on their families and care givers, and the development of an effective therapy is an important concern to health care practitioner and researchers. Although sleep disturbances in demented people could be classified into not only insomnia type but also irregular pattern type, differentiation has not yet been sufficiently practiced in a clinical setting. Demented people with irregular sleep pattern increase with progressive stage and are often insensitive to the usual pharmacotherapies for insomnia using benzodiazepines or antipsychotics. From the viewpoint of risk-benefit balance, chronotherapies such as artificial bright light or improvement of sleep hygiene could be useful and safety tools for sleep and behavioral problems in the demented elderly.     

Comparison between informant-observed and actigraphic assessments of sleep-wake rhythm disturbances in demented residents of homes for the elderly.

OBJECTIVE: Sleep-wake rhythm disturbances frequently occur in demented elderly and are of clinical relevance because they herald accelerated functional decline and institutionalization. Assessment of sleep-wake rhythm disorders is therefore of significant importance and can be performed by questionnaires or actigraphy, i.e., the recording of wrist activity. The present study investigates the relation of these two types of measurement by simultaneously assessing actigraphy and the Circadian Sleep Inventory for Normal and Pathological States (CSINAPS). METHODS: Seventy-eight elderly subjects, mean age 85+/-6 years, living in group care facilities of 12 homes for the elderly, wore an actigraph for two weeks. Caregivers completed the nurse informant CSINAPS. Spearman rank correlations and Mann-Whitney U tests were calculated over the equivalent sleep-wake rhythm parameters as derived from actigraphy and from the CSINAPS. RESULTS: Good correlations were found between questionnaire items about habitual timing of sleep and wakefulness and their actigraphic counterparts. Caregivers overestimated the actual sleep time between sleep onset and offset by 96 minutes. Questionnaire reports of sleep disturbances like wandering at night were also reflected in actigraphy parameters. However, the questionnaire and actigraphy variables correlate only modestly and may complement each other. In our study, both actigraphy and the CSINAPS seemed to miss the previously established high prevalence of sleep-disordered breathing (SDB) and leg movements during sleep (LM). CONCLUSION: The assessment of sleep and wake disturbances in demented elderly is best served by parallel use of a questionnaire like the CSINAPS and actigraphy. Moreover, if SDB and LM are a focus of interest, additional assessments are needed.     

Neuropsychological function in obstructive sleep apnoea

Patients with obstructive sleep apnoea (OSA) experience neuropsychological deficits falling broadly into the four areas of daytime sleepiness, cognitive deficits, reduced driving competence and impaired psychosocial well-being. Case-control studies of daytime function in OSA patients generally indicate moderate to severe daytime sleepiness using polysomnographic or self-rating assessments. Cognitive performance on tests of attention and concentration ability, visuomotor and constructional skills, verbal fluency, planning and problem-solving, memory and executive function may be mildly to moderately impaired. These two symptoms may contribute to a road traffic accident rate in OSA between two and seven times higher than that of normals, and to the high prevalence of minor psychiatric morbidity, and reductions in functional and health status, among patients. The daytime impairments associated with OSA are improved by continuous positive airway pressure (CPAP) therapy, although a lack of complete normalization has been suggested for objective sleepiness and some areas of cognitive function. The severity of sleepiness and cognitive impairments show weak and moderate correlations with frequency of sleep-disordered breathing in clinical and epidemiological studies. Experimental and clinical evidence supports a role for nocturnal physiological events of OSA, arousals and hypoxaemia, in directly or indirectly producing neuropsychological deficits, particularly those of sleepiness and cognitive deterioration.     

Sundowning and circadian rhythms in Alzheimer's disease

OBJECTIVE: The goal of this study was to determine changes of circadian rhythms induced by Alzheimer's disease and to explore relationships among rhythm disturbances, sundowning, and sleep disturbances in patients with Alzheimer's disease. "Sundowning" is the occurrence or exacerbation of behavioral symptoms of Alzheimer's disease in the afternoon and evening. METHOD: Circadian rhythms of core body temperature and motor activity were measured in 25 patients with diagnoses of probable Alzheimer's disease and in nine healthy individuals. The subjects with Alzheimer's disease were divided according to the occurrence of sundowning as determined by staff reports. RESULTS: The subjects with Alzheimer's disease had less diurnal motor activity, a higher percentage of nocturnal activity, lower interdaily stability of motor activity, and a later activity acrophase (time of peak) than did the healthy individuals. They also had a higher mesor (fitted mean) temperature, higher amplitude of the fitted cosine temperature curve, and later temperature acrophase than did the healthy subjects. The severity of sundowning was associated with later acrophase of temperature, less correlation of circadian temperature rhythm with a 24-hour cycle, and lower amplitude of temperature curve. CONCLUSIONS: These data indicate that Alzheimer's disease causes disturbances of circadian rhythms and that sundowning is related to a phase delay of body temperature caused by Alzheimer's disease.     

Increased skin temperature in Alzheimer’s disease is associated with sleepiness

The 24-h rhythms in sleep and temperature both change in Alzheimer's disease (AD). Characteristic changes consist of a more fragmented diurnal sleep profile with frequent nocturnal awakenings and daytime sleepiness, as well as a reduction in the amplitude of the 24-h rhythm in core body temperature (CBT). Although the 24-h rhythm in CBT is to a large extent the result of a 24-h rhythm in heat loss from the skin caused by pronounced changes in skin blood flow and consequently skin temperature (Ts), changes in the diurnal skin temperature profile in AD as compared to normal aging have remained unexplored. Because recent work indicates a causal contribution of fluctuations in skin temperature to daytime sleepiness and nocturnal sleep depth, the present study aimed to investigate the skin temperature rhythm in AD and its association with daytime sleepiness and nocturnal sleep. Ambulatory recorders were used to estimate sleep and 24-h rhythms in skin temperature in 55 AD patients and 26 matched non-demented elderly controls. Subjective sleep and daytime sleepiness were obtained using questionnaires. The results indicate that AD patients had a significantly higher daytime proximal skin temperature (PST) than elderly controls. In both AD patients and elderly controls, an elevated daytime PST was associated with more daytime sleepiness. The findings suggest a deficient downregulation of daytime proximal skin blood flow that might contribute to daytime sleepiness. Because daytime sleepiness contributes to cognitive dysfunction in AD, further research into the underlying mechanisms and possible reversibility is warranted.     

Update on disorders of sleep and the sleep--wake cycle.

Wakefulness and sleep are antagonistic states competing for the domain of brain activity. Non-REM sleep and REM sleep are different states of being, sustained by activity in brainstem nuclei, hypothalamus, basal forebrain, and thalamus. Such complex phenomenology is subject to many alterations grouped in the new International Classification of Sleep Disorders. The insomnias are the result of interacting psychosocial, psychophysiologic, neurodevelopmental, and medical factors. Proper perspective of each factor provides the clinical strategies to approach medically the symptom-complex of insomnia. The most common cause of daytime hypersomnia is chronic sleep deprivation. Obstructive sleep apnea responds to nasal CPAP, but the failure rate approaches 30%. In intolerant patients BiPAP and surgical remedies should be considered. Motor and behavioral abnormalities of sleep may be linked to REM sleep as in the REM sleep behavior disorder. Paroxysmal nocturnal dystonia and nocturnal wanderings may be associated with epilepsy. Intrusions of one state of being (wakefulness, non-REM sleep, and REM sleep) into another result in mixed, poorly defined, or only partially developed states. Dissociation of states may be responsible for confusional arousals, hallucinations, and cateplexy. Senile degeneration of the suprachiasmatic nuclei may underlie the circadian rhythm changes in old age and the "sundown" syndrome in demented patients. Misalignment of the hypothalamic pacemaker causes dysregulation of sleep-related physiologic and behavioral variables. Exposure to bright light retrains the pacemaker in night-shift workers, transmeridian travelers, and in patients with seasonal affective syndrome. Benzodiazepine compounds are very effective hypnotics, but should be used sparingly in the elderly to avoid falls, memory lapses, and aggravation of a preexisting sleep apnea syndrome. Sleep laboratory evaluations are indicated in patients with hypersomnia, suspected sleep apnea syndrome, motor-behavioral disorders of sleep, and in many individuals complaining of insomnia.     

Improvement in behavioral symptoms and advance of activity acrophase after short-term bright light treatment in severe dementia

Ten elderly subjects with severe dementia were given bright light (5000-8000 lux) for 45 min each morning for 4 weeks. Two rating scales of behavioral symptoms in dementia were used as outcome measures: Cohen-Mansfield Agitation Inventory (CMAI) and Behavior Pathology In Alzheimer's Disease Rating Scale (BEHAVE-AD), a scale for sleep-wake disturbances, and actigraphy to monitor activity rhythm. Behavioral symptoms improved with treatment. No changes in sleep-wake measures were found. There was an advance of the activity rhythm acrophase during treatment. These results suggest that short-time bright light improves behavioral symptoms and aspects of activity rhythm disturbances even in severely demented subjects.     

Fluvoxamine in the treatment of demented elderly patients: a double-blind, placebo-controlled study.

The efficacy of fluvoxamine on cognitive functioning and behavioral changes was evaluated in a double-blind, placebo-controlled study of 46 elderly demented patients. The patients had a DSM-III diagnosis of primary degenerative dementia or multi-infarct dementia and were aged greater than or equal to 65 years. Twenty-two patients were given 150 mg fluvoxamine per day and 24 received placebo tablets; 14 and 15 patients, respectively, completed 6 weeks of treatment. Within treatments, there were no significant changes in median scores on neuropsychological tests (picture recall and recognition, trail making and finger tapping) or the GBS scale scores (degrees of dementia) or GBS subscale score (clinical profiles, including symptoms common in dementia, motor, emotional and intellectual functioning). Between treatments, the median changes in psychometric test scores did not differ significantly. However, within and between treatments, there were trends favoring fluvoxamine on symptoms common in dementia (confusion, irritability, anxiety, fear-panic, mood level and restlessness). In conclusion, the study does not support the hypothesis that fluvoxamine improves cognitive functioning or behavioral changes in elderly dementia patients.     

Association between changes in adrenal secretion and cerebral morphometric correlates in normal aging and senile dementia

The circadian organization of adrenal secretion was studied in 23 healthy elderly subjects, 23 elderly demented patients and 10 healthy young subjects, in order to investigate the relationships between the hypothalamic-pituitary-adrenal axis and some cerebral morphometric parameters. The cerebral morphometric analysis was performed in some subjects of the three groups by MRI. A significant increase in cortisol levels during evening and nighttime was found in both groups of the aged subjects. In elderly subjects, particularly if demented, the mean serum dehydroepiandrosterone sulfate (DHEAs) levels throughout the 24-hour cycle were significantly lower than in young controls. A significant reduction of the hippocampal and temporal volume and an enlargement of the lateral ventricles were found in aged subjects, these changes being significantly related to subjects' age. Moreover, the hippocampal volume was positively correlated with the circadian mesor of DHEAs (i.e., the circadian rhythm adjusted mean) and with the cortisol nocturnal increase. Our data may suggest the existence of a link between the selective impairment of cortisol secretion and DHEAs levels, and the progression of hippocampal degeneration.     

Melatonin secretion rhythm disorders in patients with senile dementia of Alzheimer's type with disturbed sleep-waking.

BACKGROUND: There is growing evidence that the dysregulation of circadian rhythms may play an important role in irregular sleep-waking in demented elderly. In this study, we investigated daily variation of the pineal hormone melatonin, which has been reported to possess hypnogenic and synchronizing effects, in patients with senile dementia of Alzheimer's type. METHODS: Serum melatonin secretion rhythms in inpatients with senile dementia of Alzheimer's type (SDAT group, n = 10, average age = 75.7 years) with disturbed sleep-waking and nondemented elderly (ND group, n = 10, age = 78.3 years) without clinical sleep disorders in the same facility were monitored under a dim light condition without excessive physical exercise. RESULTS: The SDAT group showed a significantly higher degree of irregularities in actigraphically recorded rest-activity (R-A) rhythm during the 7-day baseline period compared with the ND group. The SDAT group simultaneously showed significantly reduced amplitude, larger variation of peak times, and diminished amount of total secretion in the melatonin secretion rhythm compared with the ND group. There were significantly positive correlations between the severity of R-A rhythm disorder and the reduced amplitude as well as diminished amount of total melatonin secretion. CONCLUSIONS: The SDAT patients with disturbed sleep-waking possessed melatonin secretion rhythm disorders that may play an important role in irregular sleep-waking in demented elderly.     

Well-being in patients with chronic fatigue syndrome: the role of acceptance

OBJECTIVE: Research in chronic pain patients has shown that accepting the chronic nature of their illness is positively related to quality of life. The aim of this study was to investigate whether acceptance is also associated with better well-being in patients suffering from chronic fatigue syndrome (CFS). METHODS: Ninety-seven patients completed a battery of questionnaires measuring fatigue, functional impairment, psychological distress, and acceptance. RESULTS: Results indicated that acceptance has a positive effect upon fatigue and psychological aspects of well-being. More specifically, acceptance was related to more emotional stability and less psychological distress, beyond the effects of demographic variables, and fatigue severity. CONCLUSION: We suggest that promoting acceptance in patients with CFS may often be more beneficial than trying to control largely uncontrollable symptoms.     

Daytime sleepiness is associated with dementia and cognitive decline in older Italian adults: A population-based study

ObjectiveThe occurrence of dementia among the elderly has been associated with several, often not modifiable, risk factors. Recent epidemiological studies focused their interest on a possible association between cognitive decline and sleep, a potentially modifiable risk factor. Due to controversial results and limitations of the previous studies, we decided to reexamine the relationship between disturbed sleep and cognitive impairment in the elderly.MethodsSeven hundred fifty subjects aged 65 years or older were recruited. The Mini-Mental State Examination (MMSE) and the Global Deterioration Scale (GDS) scores were used to evaluate the severity of cognitive decline. Diagnosis of dementia was made by means of the DSM-IV criteria. The older adults were interviewed in order to assess the presence of several sleep complaints (insomnia, snoring and/or witnessed sleep apneas, restlessness and/or leg jerks, sleepwalking and nightmares). Excessive daytime sleepiness was evaluated by means of a validated questionnaire. The principal caregiver of each older adult took part in the interview, providing the information if the subject was unable to answer because of mental impairment.ResultsEighty-six individuals were diagnosed as demented; a large part of them (47.8%), in particular, were recognized as being affected by Alzheimer’s disease. The prevalence of each sleep complaint in the older adults was as follows: insomnia 84.7%, snoring and/or witnessed sleep apneas 26.2%, restlessness and/or jerks in the legs 25.7%, sleepwalking 0.5%, nightmares 6.4% and daytime somnolence 30.6%. Among sleep disturbances, excessive daytime sleepiness was independently associated with the presence of dementia in the elderly. In addition, the frequency of excessive daytime sleepiness increased progressively across the different categories of cognitive decline, as measured by means of MMSE and GDS scores.ConclusionsInsomnia, the most common sleep complaint in our sample, was not associated with the presence of cognitive decline. As opposed to insomnia, excessive daytime sleepiness was significantly related to dementia. Further studies are needed in order to investigate the direction of this association and to evaluate the possible role of daytime somnolence as an early marker of neurodegenerative disease, particularly Alzheimer’s disease, in some older adults.     

Assessment and prediction of outcome for a brief behavioral insomnia treatment program

This study examined (a) the efficacy, and (b) predictors of outcome of a brief (one to four sessions) behavioral treatment program for chronic insomnia. A total of 103 insomnia patients were treated, and outcome was assessed by a follow-up questionnaire. Outcome variables, including both nocturnal sleep parameters and measures of daytime functioning, showed significant improvement subsequent to treatment. Pretreatment sleep hygiene practices were significantly correlated with daytime fatigue and sleep latency outcome factors. Pre-and post-treatment complaints of daytime fatigue were associated with somatic complaints in general, but not with nocturnal sleep variables. Explanatory hypothesis are discussed.     

Discrete dynamic Bayesian network analysis of fMRI data

We examine the efficacy of using discrete Dynamic Bayesian Networks (dDBNs), a data-driven modeling technique employed in machine learning, to identify functional correlations among neuroanatomical regions of interest. Unlike many neuroimaging analysis techniques, this method is not limited by linear and/or Gaussian noise assumptions. It achieves this by modeling the time series of neuroanatomical regions as discrete, as opposed to continuous, random variables with multinomial distributions. We demonstrated this method using an fMRI dataset collected from healthy and demented elderly subjects (Buckner, et al., 2000: J Cogn Neurosci 12:24-34) and identify correlates based on a diagnosis of dementia. The results are validated in three ways. First, the elicited correlates are shown to be robust over leave-one-out cross-validation and, via a Fourier bootstrapping method, that they were not likely due to random chance. Second, the dDBNs identified correlates that would be expected given the experimental paradigm. Third, the dDBN's ability to predict dementia is competitive with two commonly employed machine-learning classifiers: the support vector machine and the Gaussian naive Bayesian network. We also verify that the dDBN selects correlates based on non-linear criteria. Finally, we provide a brief analysis of the correlates elicited from Buckner et al.'s data that suggests that demented elderly subjects have reduced involvement of entorhinal and occipital cortex and greater involvement of the parietal lobe and amygdala in brain activity compared with healthy elderly (as measured via functional correlations among BOLD measurements). Limitations and extensions to the dDBN method are discussed.     

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.     

Objective investigation of the sleep–wake cycle in adults with intellectual disabilities and autistic spectrum disorders

Background Disturbances in circadian rhythm functioning, as manifest in abnormal sleep–wake cycles, have been postulated to be present in people with autistic spectrum disorders (ASDs). To date, research into the sleep–wake cycle in people with ASDs has been primarily dependant on third‐party data collection. Method The utilization of non‐invasive objective recording technologies such as actigraphy permits investigation of both sleep and circadian rhythm functioning in people with ASDs, together with the collection of data on daytime activity. Results Data were collected from 31 participants with intellectual disabilities living in supported community‐based residential provision aged between 20 and 58 years, of whom 14 had an ASD. Analysis indicated that there were no significant differences in sleep patterns and circadian rhythm function between those participants with an ASD and those without. Conclusions The mean scores of the participants as a whole indicated abnormalities in the two key circadian rhythm parameters of interdaily stability and intradaily variability. The implications of these findings for both clinical practice and theory are discussed.     

Impaired affective prosody in AD: relationship to aphasic deficits and emotional behaviors.

OBJECTIVE: To assess the ability of patients with AD to produce, repeat, and comprehend affective prosody in relationship to severity of dementia, aphasic deficits, and changes in emotional behaviors. METHODS: An Aprosodia Battery was used to assess affective-prosodic performance and to identify patterns of deficits in affective communication. In addition, the presence and severity of aberrant behaviors, depression, and aphasia were assessed using standardized assessment tools. RESULTS: Patients with AD had significant impairments in their ability to repeat, comprehend, and discriminate affective aspects of speech, but maintained normal spontaneous affective-prosodic performances. As dementia severity increased, performance on the comprehension tasks and, to a lesser degree, on the repetition tasks became more impaired; spontaneous affective prosody remained normal. In the current study, affective-prosodic comprehension impairments were present in patients with all stages of AD; comparable aphasic deficits were not observed until patients were severely demented. The majority of aphasic deficits involved anomia without loss of comprehension. Patients with AD with sensory aprosodia had increased frequency and severity of behavioral changes whereas patients with AD with normal affective-prosodic performance were significantly less demented, had normal linguistic ability, and displayed fewer aberrant psychiatric behaviors. CONCLUSION: Patients with mild AD are at considerable risk for affective-prosodic comprehension deficits. As patients become more demented and develop sensory aprosodia, they are at greater risk for disturbances in behavior and mood.     

Morning bright light therapy for sleep and behavior disorders in elderly patients with dementia

Fourteen inpatients with dementia showing sleep and behavior disorders (average age = 75 years), and 10 control elderly people (average age = 75 years) were carefully observed for 2 months. Four weeks of morning light therapy markedly improved sleep and behavior disorders in the dementia group. The measurement of sleep time and the serum melatonin values suggests that sleep and behavior disorders in the dementia group are related to decreases in the amplitude of the sleep-wake rhythm and decreases in the levels of melatonin secretions. Morning light therapy significantly increased total and nocturnal sleep time and significantly decreased daytime sleep time. These results indicate that morning bright light is a powerful synchronizer that can normalize disturbed sleep and substantially reduce the frequency of behavior disorders in elderly people with dementia.     

Cortisol and Alzheimer's disease, I: Basal studies

Patients with Alzheimer's disease and nondemented elderly control subjects participated in studies of cortisol secretion during sleep and at 9:00 a.m. and were given dexamethasone suppression tests (DSTs) and lumbar punctures. Nocturnal and 9:00 a.m. cortisol concentrations were significantly higher in the demented patients. CSF MHPG negatively correlated with mean nocturnal cortisol. The most severely demented patients had the highest 9:00 a.m. and mean nocturnal cortisol concentrations. DST results did not distinguish samples with substantially different nocturnal cortisol concentrations. These results suggest that measurements of basal plasma cortisol concentrations and dexamethasone suppression provide different information but support the notion of somewhat higher than normal cortisol concentrations in Alzheimer's disease patients.     

A case-control study on psychological symptoms in sleep apnea-hypopnea syndrome.

OBJECTIVES: To investigate the psychological status of patients with sleep apnea-hypopnea syndrome (SAHS) and to evaluate the association of SAHS with psychological symptoms, using the Symptom Checklist-90 (SCL-90) scale. METHODS: The study comprised 30 SAHS patients (25 men, 5 women) and 30 matched, healthy control subjects. They all completed the SCL-90 and the Epworth Sleep Scale (ESS) and underwent a whole-night polysomnographic (PSG) examination. We used t-tests for group comparisons of nocturnal PSG characteristics, daytime sleepiness, and psychological symptoms. We employed Spearman's rank correlation analysis to indicate the effects of several nocturnal PSG variables (for example, total sleep time, percentage of wake at sleep, Apnea and Hypopnea Index [AHI], and oxygen desaturation) or subjective daytime sleepiness on psychological symptoms in SAHS. RESULTS: SAHS patients suffered from fragmented sleep and decreased arterial oxygen saturations, compared with healthy control subjects. The General Severity Index (GSI) of SCL-90 was significantly higher in SAHS patients than in healthy control subjects, as were measures of somatization, obsession-compulsion, depression, anxiety, and hostility (P < 0.05). The severity of psychological symptoms in SAHS patients was negatively related to total sleep time and percentage of stage 2 nonrapid eye movement (NREM) sleep; it was positively related to percentage of wake time after sleep onset, percentage of stage 1 NREM sleep, and ESS scores. CONCLUSION: In our study population, SAHS patients had decreased psychological well-being, which could be explained by fragmented sleep or excessive daytime sleepiness.