Bright light treatment for sleep–wake disturbances in aged individuals with dementia

Treatment using bright light exposure was carried out on six aged subjects with dementia in two nursing homes. Sleep logs were recorded by the staff. Bright light treatment was applied in the late morning every day. The %sleep in the lights-out period and/or the %wake in daytime increased in three subjects. In the other three subjects, sleep onset time was advanced. In all subjects abnormal behavior episodes around the lights-out time tended to be reduced. These results suggest that bright light treatment is effective in improving the sleep-wake disturbances of aged individuals with dementia.     

Daily rhythm of serum melatonin in patients with dementia of the degenerate type

The daily rhythm in serum melatonin levels was measured in patients with dementia of the degenerate type (Alzheimer's disease, Pick's disease and senile dementia of the Alzheimer type) by radioimmunoassay. Thirteen patients (age: 69.0 ± 8.0 years, mean ± S.D.) were studied. All patients were hospitalized at the time of the study and had a history of sleep-wake disturbances, nocturnal wandering and/or delirium. We also studied 13 age-matched healthy control subjects (control group 1), ten young adults (control group 2), and nine hospitalized patients without dementia (control group 3). Two subjects in the control groups showed no measurable changes in melatonin level throughout the day, while the other 30 control subjects exhibited a clear daily rhythm with the peak concentration occurring during the night. On the other hand, four out of the 13 patients with dementia did not show any melatonin rhythm. Two of the demented patients who did not exhibit melatonin rhythm displayed clinical symptoms of rhythm disorders. One out of the nine patients with melatonin rhythm presented with clinical symptoms, such as delirium and sleep-wake disturbance. Our results suggest that the probability of absent melatonin rhythm is higher in demented patients compared with subjects without dementia. However, a lack of melatonin rhythm is not always associated with symptomatic rhythm disorders. Since the melatonin rhythm reflects that of the suprachiasmatic nucleus, it follows that the SCN function of the patients having a history of rhythm disorders was not always severely damaged.     

Bright light treatment of behavioral and sleep disturbances in patients with Alzheimer's disease.

OBJECTIVE: The authors tested the hypothesis that evening bright light pulses would improve sleep-wake patterns and reduce agitation in patients with Alzheimer's disease who have severe sundowning (a syndrome of recurring confusion and increased agitation in the late afternoon or early evening) and sleep disorders. METHOD: Ten inpatients with Alzheimer's disease on a research ward of a veterans' hospital were studied in an open clinical trial. All patients had sundowning behavior and sleep disturbances. After a week of baseline measurements, patients received 2 hours/day of exposure to bright light between 7:00 p.m. and 9:00 p.m. for 1 week. During the baseline week, the treatment week, and a posttreatment week, patients were rated by nurses for agitation, sleep-wake patterns, use of restraints, and use of prescribed-as-needed medication. On the last 2 days of each week, patients wore activity monitors. Activity counts were analyzed for circadian rhythmicity. RESULTS: Clinical ratings of sleep-wakefulness on the evening nursing shift improved with light treatment in eight of the 10 patients. The proportion of total daily activity occurring during the nighttime decreased during the light-treatment week. The relative amplitude of the circadian locomotor activity rhythm, a measure of its stability, increased during the light-treatment week. More severe sundowning at baseline predicted greater clinical improvement. CONCLUSIONS: Evening bright light pulses may ameliorate sleep-wake cycle disturbances in some patients with Alzheimer's disease. This effect may be mediated through a chronobiological mechanism.     

Predictors of circadian sleep-wake rhythm maintenance in elders with dementia

Minimal data exists to predict which elders with dementia in nursing homes will maintain circadian sleep-wake rhythms during senescence and which elders with dementia in nursing homes will experience sleep-wake rhythm deterioration. This circadian deterioration is one of the background factors identified in the Needs-driven Dementia-compromised Behavior Model. The objective of this study was to determine predictors of circadian sleep-wake rhythm maintenance in elders with dementia residing in nursing homes. This secondary analysis identifies predictors of maintaining circadian sleep-wake rhythm in a convenience sample of 171 elders with dementia residing in seven nursing homes in the Southern United States. An autocorrelogram of the circadian sleep-wake rhythm for each participant determined whether or not the rhythm had deteriorated. Using measures of depression, cognitive function, physical and psychosocial activity, medications, and sleep apnea, as well as demographic characteristics of the sample, logistic regression determined the best predictors of rhythm maintenance. The best predictors of circadian sleep-wake rhythm maintenance in elders with dementia residing in nursing homes were physical activity (p = 0.00) and psychosocial activity (p = 0.00). The interaction term between these variables was not significant (p = 0.24). These findings suggest that providing meaningful daytime physical and psychosocial activity may assist in maintaining circadian sleep-wake rhythmicity. Additional research is needed to determine if these interventions would improve circadian sleep-wake rhythm in elders with dementia residing in nursing homes.     

The Management of Sleep and Circadian Disturbance in Patients with Dementia

Sleep and circadian disturbances are common among patients with dementia. Symptomatic manifestations vary according to dementia subtype, with one commonly shared pattern—the irregular sleep-wake rhythm (ISWR), a circadian disorder characterized by an absence of the sleep-wake cycle’s circadian synchronization. Hypothesized mechanisms of circadian rhythm disturbance include suprachiasmatic nucleus (SCN) circadian pacemaker damage, pineal gland and melatonin secretion alterations, and reduced zeitbeigers and decreased input to the SCN. Management options include prescribed sleep/wake scheduling, light therapy, melatonin, physical and social activity, and mixed modality. The mixed-modality approach is the most effective method in treating ISWR. Pharmacologic interventions are controversial, with no evidence supporting their effectiveness while associated with multiple side effects. They should be used with caution and only be considered as short-term therapy. All treatment strategies should be individualized to achieve the best outcomes.     

Effects of bright light on cognitive and sleep-wake (circadian) rhythm disturbances in Alzheimer-type dementia

Twenty-seven patients with Alzheimer-type dementia (ATD) were treated with bright light therapy in the morning for four consecutive weeks. The cognitive state of each patient was evaluated with the Mini-Mental-State Examination (MMSE) and circadian rhythm with actigram before and after therapy for all of the patients and those of two groups divided by the severity criteria of the Clinical Dementia Rating. The therapy improved the circadian rhythm disturbances. Although the therapy caused no remarkable effects on dementia severity, it improved the MMSE scores, especially in the early stages of ATD. These results suggest that bright light therapy improved the circadian rhythm disturbances and then bettered the cognitive state in early-stage ATD.     

Effects of risperidone on behavioral and psychological symptoms associated with dementia in clinical practice

BACKGROUND: Risperidone significantly improves behavioral and psychological symptoms of dementia (BPSD), including aggression, agitation and psychosis, as shown by randomized, placebo-controlled trials. METHODS: An 8-week, multicenter, naturalistic, open-label study was carried out to examine whether the benefits of risperidone apply to clinical practice. A total of 4499 patients were treated with risperidone at flexible doses chosen by physicians, and were included in the safety evaluation. Of these, 3909 patients met the intended study criteria (at least 65 years of age, dementia, and the presence of BPSD) and were included in the efficacy analyses. RESULTS: At the end of the study (after 8 weeks of treatment), risperidone (average final dose 1.6 mg/day) significantly improved all symptoms studied (agitation, aggressiveness, disturbance of the sleep-wake rhythm, social withdrawal, suspiciousness and delusions) as rated by physicians on a five-point scale of severity. On a four-point scale of global efficacy, more than 90% of patients were rated improved by both physicians and caregivers after 8 weeks of treatment. A significant improvement in sleep-wake cycle disturbances was also noted. A total of 422 adverse events were documented in 346 of the 4499 patients (7.7%); these included insufficient efficacy (2.6%), extrapyramidal symptoms (0.89%), deterioration of psychiatric symptoms (0.73%), sedation (0.56%), gastrointestinal disturbances (0.49%), cardiovascular disorders (0.38%), and cerebrovascular adverse events (0.36%). CONCLUSIONS: Risperidone is an effective and well-tolerated treatment for BPSD in routine clinical practice.     

Trials of bright light exposure and melatonin administration in a patient with non-24 hour sleep-wake syndrome

Abstract We report a patient with non-24 h sleep-wake syndrome (non-24) whose free-running sleep-wake cycle was successfully treated with both scheduled bright light exposure and melatonin treatment. In the present study, morning bright light as well as evening melatonin phase-advanced sleep-wake cycles and melatonin rhythm. Both these procedures achieved appropriate entrainment to a 24 h day. However, the patient did not continue morning bright light therapy after the discharge. Rising at appropriate times in the morning for bright light therapy was difficult for him to continue. Melatonin treatment was better tolerated because of its ease of application.     

A randomized, controlled trial of bright light therapy for agitated behaviors in dementia patients residing in long-term care.

BACKGROUND: Agitated behaviors are common in dementia patients residing in chronic care settings. Their occurrence may be associated with lack of adequate exposure to sunlight and with circadian rhythm disturbances.OBJECTIVE: Prior research has suggested that bright light therapy (BLT) may reduce agitated behaviors in dementia patients. The aim of this study was to test the efficacy of BLT in a randomized, controlled, crossover clinical trial. METHOD: Fifteen patients with dementia and agitated behaviors residing in a chronic care facility were randomized in a crossover design to morning BLT for 1 hour per day or to a control condition with dim light exposure. Patients were treated in either condition for 4 weeks, followed by 1 week on no treatment, prior to being crossed over to the other condition. RESULTS: Eight out of 15 patients completed the entire study. The rest completed at least 2 weeks of study. Patients randomized to the BLT condition exhibited a statistically significant improvement in nocturnal sleep from a mean of 6.4 hours/night to 8.1 hours/night 4 weeks later (p<0.05). The sleep of patients in the control condition did not improve significantly. There were no other significant differences between baseline and follow-up, nor between BLT and control treated patients on the other outcome measures, which included the Behavioral Pathology in Alzheimer Disease scale (Behave-AD) and the Cornell Scale for Depression in Dementia. CONCLUSION: Patients with dementia in chronic care who exhibit agitated behaviors sleep more hours at night when administered morning BLT. However, BLT does not lead to improvements in agitated behaviors in institutionalized patients with dementia with non-disturbed sleep-wake cycles.     

Behavioral profile of Alzheimer's disease in Chinese elderly--a validation study of the Chinese version of the Alzheimer's disease behavioral pathology rating scale

OBJECTIVES: This study aims to examine the psychometric properties of the Chinese version of the Alzheimer's disease behavioral pathology rating scale (CBehave-AD) and the behavioral profile of Chinese patients with AD. METHODS: Seventy-one subjects with NINCDS-ADRDA diagnosis of probable and possible AD were assessed for validation of the CBehave-AD. A behavioral symptom frequency checklist, the Chinese version of the Blessed Roth dementia scale (CDS) and the Cantonese version of the Mini-Mental State Examination (CMMSE) were used for comparison. An extended sample of 120 AD patients was then evaluated with the CBehave-AD. RESULTS: High correlations between the CBehave-AD and checklist scores were found (paranoid and delusional ideation, hallucinations, activity disturbances, aggressiveness and diurnal rhythm disturbances). The scale also demonstrated satisfactory inter-rater and test-retest reliabilities. The mean (SD) CMMSE score of the 120 patients was 9.4 (7.1). Among them, 32% have delusions, 15% had hallucinations, 54% had activity disturbances, 61% had aggressive behavior, 44% had sleep disturbance, 24% had affective disturbances, 19% had anxiety and phobias. Delusional ideation was significantly associated with hallucinations, aggressiveness, and affective disturbances. Diurnal rhythm disturbances were associated with activity disturbances and aggressiveness. CBehave-AD total scores were not significantly correlated with severity of AD, but individual symptom categories showed different pattern of correlation. Delusions, hallucinations, anxiety and phobias were significantly correlated with dementia staging. CONCLUSION: The findings suggest that the CBehave-AD is a valid assessment tool for behavioral disturbances in patients with AD. Variable associations between different symptom categories and dementia staging suggest a need for further exploration of the complex interactions between behavioral and cognitive disturbances in dementia.     

Etiology and treatment of intrinsic circadian rhythm sleep disorders

Some individuals experience an acute or chronic sleep disturbance, associated with a misalignment between the timing of their sleep and the sleep-wake cycle that is desired, or considered normal by society. It is estimated that 5-10% of insomniacs seeking treatment have this type of disorder, collectively called circadian rhythm sleep disorders. This paper reviews circadian rhythm sleep disorders of the intrinsic type, which include delayed sleep phase syndrome, advanced sleep phase syndrome, non-24-hour sleep-wake syndrome, and irregular sleep-wake pattern. For each disorder, we present data addressing its pathophysiology and potential treatments, including the use of behavioral measures and chronotherapy, bright light treatment and pharmacological treatments such as melatonin. We conclude by addressing some of the limitations and drawbacks of the various treatments.     

Treatment of sleep and nighttime disturbances in Alzheimer's disease: a behavior management approach

BACKGROUND AND PURPOSES: Sleep and nighttime behavioral disturbances are widespread in community-dwelling dementia patients, but little is known about the usefulness of behavioral interventions for treating them. This article presents data from three cases enrolled in an ongoing study of sleep problems in community-dwelling Alzheimer's disease (AD) patients: nighttime insomnia treatment and education for Alzheimer's disease. PATIENTS AND METHODS: All subjects received written materials describing age- and dementia-related changes in sleep, and standard principles of good sleep hygiene. Caregivers also received education about dementia, listings of relevant community resources, and general support. Subjects' sleep-wake activity was measured at baseline, post-test (2 months), and 6-month follow-up using an Actillume wrist-movement recorder, which was worn continuously for 1 week. RESULTS: Post-test actigraphic improvements in sleep quantity and sleep efficiency, number of nighttime awakenings, and amount of daytime sleep, as well as subjective sleep ratings were observed. One subject maintained improvements at 6-month follow-up. Subjects varied widely in the type of sleep problems reported and behavioral strategies implemented by family caregivers, illustrating the complexity that characterizes nighttime behavioral disturbances in AD. CONCLUSIONS: This paper provides clinical and empirical evidences that behavioral strategies including standard sleep hygiene recommendations can be helpful in treating sleep and nighttime behavioral disturbances in dementia patients.     

Effect of timed bright light treatment for rest-activity disruption in institutionalized patients with Alzheimer's disease

BACKGROUND: Disturbances in rest-activity rhythm are prominent and disabling symptoms in Alzheimer's disease (AD). Nighttime sleep is severely fragmented and daytime activity is disrupted by multiple napping episodes. In most institutional environments, light levels are very low and may not be sufficient to entrain the circadian clock to the 24-hour day. METHOD: The purpose of this randomized clinical trial was to test the effectiveness of timed bright light therapy in reducing rest-activity (circadian) disruption in institutionalized patients with AD. The experimental groups received either morning (9.30-10.30 am) or afternoon (3.30-4.30 pm) bright light exposure ( > or = 2500 lux in gaze direction) Monday through Friday for 10 weeks. The control group received usual indoor light (150-200 lux). Nighttime sleep, daytime wake, and rest-activity parameters were determined by actigraphy. Repeated measures analysis of variance was employed to test the primary study hypotheses. RESULTS: Seventy institutionalized subjects with AD (mean age 84) completed the study. No significant differences in actigraphy-based measures of nighttime sleep or daytime wake were found between groups. Subjects in either experimental light condition evidenced a significantly (p < 0.01) more stable rest-activity rhythm acrophase over the 10-week treatment period compared to the control subjects whose rhythm phase delayed by over two hours. CONCLUSIONS: One hour of bright light, administered to subjects with AD either in the morning or afternoon, did not improve nighttime sleep or daytime wake compared to a control group of similar subjects. However, exposure to one-hour of bright light in either the morning or afternoon may provide sufficient additional input to the circadian pacemaker to facilitate entrainment to the 24-hour day.     

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.     

Photoacoustic treatment mitigates cognitive dysfunction in a model of sleep-wake rhythm disturbance

Sleep-wake rhythm disturbances,which are characterized by abnormal sleep timing or duration,are associated with cognitive dysfunction.Photoacoustic treatments including light and sound stimulation have been found to be effective in modulating sleep patterns and improving cognitive behavior in abnormal sleep-wake pattern experiments.In this study,we examined whether light and sound interventions could reduce sleep-wake pattern disturbances and memory deficits in a sleep rhythm disturbance model.We established a model of sleep rhythm disturbance in C57 BL/6 J mice via a sleep deprivation method involving manual cage tapping,cage jostling,and nest disturbance.We used a Mini Mitter radio transmitter device to monitor motor activity in the mice and fear conditioning tests to assess cognitive function.Our results indicated that an intervention in which the mice were exposed to blue light(40-Hz flickering frequency)for 1 hour during their subjective daytime significantly improved the 24-hour-acrophase shift and reduced the degree of memory deficit induced by sleep deprivation.However,interventions in which the mice were exposed to a 40-Hz blue light at offset time or subjective night time points,as well as 2 Hz-blue light at 3 intervention time points(subjective day time,subjective night time,and offset time points),had no positive effects on circadian rhythm shift or memory deficits.Additionally,a 2000-Hz sound intervention during subjective day time attenuated the24-hour-acrophase shift and memory decline,while 440-Hz and 4000-Hz sounds had no effect on circadian rhythms.Overall,these results demonstrate that photoacoustic treatment effectively corrected abnormal sleep-wake patterns and cognitive dysfunction associated with sleep-deprivation-induced disturbances in sleep-wake rhythm.All animal experiments were approved by the Experimental Animal Ethics Committee of Drum Tower Hospital Affiliated to the Medical College of Nanjing University,China(approval No.20171102)on November20,2017.     

An activity monitor study on the sleep-wake rhythm of healthy aged people residing in their homes

Abstract The aim of this preliminary study was to investigate sleep-wake rhythm in active, healthy elderly people residing in their usual habitat. The subjects were thirty-five male volunteers within an age range of 65–95 for 3–4 days. We measured the sleep-wake rhythm of the subjects with an Actillume® which is a combined wrist activity monitor and illumination recorder. Analysis of the Actillume® recording showed that 24 of the 35 subjects (69%) kept continuous activity indicating good maintenance of wakefulness with high light exposure. The mean mesor of sleep-wake rhythm, however, significantly decreased in the older subjects (aged 80–95; n = 15).     

Actigraphy in patients with seasonal affective disorder and healthy control subjects treated with light therapy.

BACKGROUND: Abnormalities of the circadian rest-activity cycle are hypothesized to accompany the clinical picture of seasonal affective disorder (SAD). The purpose of this study was to investigate if bright light therapy (BLT) is able to reverse these disturbances. METHODS: Seventeen SAD outpatients and 17 sex- and age-matched healthy control subjects were treated with BLT administered in the morning for 4 weeks. Activity levels were measured with wrist actigraphy. RESULTS: SAD patients had 33% lower total (p = .031) and 43% lower daylight activity (p = .006) in week 1 compared with control subjects. The relative amplitude of the sleep-wake cycle was attenuated by 6% in patients (p = .025); they were phase delayed by 55 minutes (p = .023) and had significantly lower sleep efficiency (p = .030). Total (p = .002) and daylight activity (p = .001) increased after 4 weeks of treatment in SAD patients. Moreover, BLT led to increase of relative amplitude (p = .005), advance of delayed rhythms (p = .036), and improved sleep efficiency (p = .011) in patients. Intradaily stability, measuring the strength of coupling of the rhythm to external zeitgebers, increased by 9% both in patients and healthy control subjects (p = .032). CONCLUSIONS: Treatment with BLT normalizes disturbed activity patterns and restores circadian rhythms in SAD patients. BLT might also stabilize the circadian rhythm in nondepressed individuals during the fall-winter season.     

Quetiapine treatment for behavioral and psychological symptoms in patients with senile dementia of Alzheimer type

The purpose of this study was to assess the effect of quetiapine in the treatment of behavioral and psychological symptoms of dementia (BPSD) in patients with senile dementia of Alzheimer type (SDAT). Sixteen SDAT patients with BPSD were recruited and quetiapine (25- 200 mg/day) was prescribed for 8 weeks. BPSD were evaluated with the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) and Cohen-Mansfield Agitation Inventory (CMAI) at week 0 (baseline) and week 8 (endpoint). The severity of the extrapyramidal symptoms was also assessed by the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) at baseline and endpoint. Significant improvements were seen in the CMAI total score and in the BEHAVE-AD subscales of delusions, activity disturbances, aggressiveness, diurnal rhythm disturbances and in the BEHAVE-AD overall severity. There was no significant difference between the baseline and endpoint in the DIEPSS score. These data indicate that quetiapine is effective in controlling BPSD with favorable adverse-event profiles.     

Effect of light on agitation in institutionalized patients with severe Alzheimer disease.

OBJECTIVE: Preliminary data suggest that morning bright light might improve symptoms of agitation, a serious problem in patients with dementia. The authors expand on an earlier pilot study by evaluating the effect of bright light therapy on agitated behavior in a large sample of patients with severe dementia. METHODS: Ninety-two patients were randomly assigned to morning bright light, morning dim red light, or evening bright light. Agitation was rated by research staff who observed the patients every 15 minutes throughout the treatment period and by caregivers at one time-point before and one time-point after treatment. RESULTS: Morning bright light delayed the acrophase of the agitation rhythm by over 1.5 hours. Bright light was associated with improved caregivers' ratings but had little effect on observational ratings of agitation. CONCLUSION: Although the result that light shifted the peak of the agitated behavior might be generalizable to patients with milder forms of AD, the fact that agitation was not ameliorated might not be. Because the suprachiasmatic nucleus (SCN) of patients with severe AD is likely to be more degenerated, and the circadian activity rhythms deteriorate as the disease progresses, it is still possible that patients with more intact SCNs, that is, patients with mild or moderate AD, might benefit from light treatment even more than those with severe AD.     

Evaluation of risperidone in the treatment of behavioral and psychological symptoms and sleep disturbances associated with dementia

BACKGROUND: Dementia is associated with progressive cognitive impairment and behavioral and psychological symptoms. Sleep-wake cycle disturbances are common in patients with dementia. This study evaluated the efficacy and safety of risperidone in the treatment of the behavioral and psychological symptoms of dementia (BPSD) and associated sleep-wake cycle disturbances. METHODS: In this open-label, 12-week, observational, prospective study, the effects of risperidone were assessed using the Neuropsychiatric Inventory (NPI) total and subscale scores. Sleep-wake cycle disturbances were rated by patients/caregivers using a newly developed sleep behavior questionnaire that included assessment of sleep duration, quality, awakenings, and effects on daily activities. Tolerability assessments included the Udvalg for Kliniske Undersogelser (UKU) subscale for extrapyramidal symptoms (EPS) and the recording of adverse events. RESULTS: A total of 338 patients entered the study, with 321 patients completing. Following 12 weeks of risperidone treatment (mean dose 1.49 mg/day at end-point), the mean NPI score was reduced to 10.6 from a baseline score of 28.7. Compared with baseline, patients/caregivers reported significant improvements following 12 weeks of risperidone in total sleep hours at night (5.5 vs. 7.1 hours), hours awake in bed at night (2.3 vs. 1.2 hours), insomnia (40.1% vs. 8.4%), and other sleep-related variables. Six patients reported a total of 10 adverse events, including somnolence (n = 3) and sialorrhea (n = 2). Scores on the UKU subscale of EPS improved significantly (mean 4.0 at baseline vs. 1.7 at week 12). CONCLUSIONS: Risperidone is effective and well tolerated in the treatment of BPSD and associated sleep disturbances.