Circadian Rhythm Sleep-Wake Disorders in Older Adults.

The timing, duration, and consolidation of sleep result from the interaction of the circadian timing system with a sleep-wake homeostatic process. When aligned and functioning optimally, this allows for wakefulness throughout the day and a long consolidated sleep episode at night. Changes to either the sleep regulatory process or how they interact can result in an inability to fall asleep at the desired time, difficulty remaining asleep, waking too early, and/or difficulty remaining awake throughout the day. This mismatch between the desired timing of sleep and the ability to fall asleep and remain asleep is a hallmark of a class of sleep disorders called the circadian rhythm sleep-wake disorders. In this updated article, we discuss typical changes in the circadian regulation of sleep with aging; how age influences the prevalence, diagnosis, and treatment of circadian rhythm sleep disorders; and how neurologic diseases in older patient impact circadian rhythms and sleep.

Sleep deprivation therapy to reset the circadian pacemaker in a non-24-hour sleep-wake disorder: a case report.

NONE: Non-24-hour sleep-wake disorder is 1 of several chronic circadian rhythm sleep-wake disorders. It is defined as progressive daily shifts in sleep onset and wake times. It mainly affects patients who are sight-impaired, is relatively rare in sighted patients, and is difficult to treat, with no guidelines. This case report discusses non-24-hour sleep-wake disorder in a sighted young man who complained of alternating severe insomnia and excessive sleepiness, with a sleep agenda and actigraphic data showing a daily delay of approximately 2 hours. A novel therapy by total sleep deprivation followed by a combination of morning light therapy and nocturnal melatonin administration was efficient in stopping his free-running sleep-wake pattern both immediately and in the long term. The treatment combination for 6 months resulted in stable circadian entrainment to a 24-hour cycle. Compliance with chronotherapy was maintained over the course of follow-up.

Light therapies to improve sleep in intrinsic circadian rhythm sleep disorders and neuro-psychiatric illness: A systematic review and meta-analysis.

Circadian dysregulation causes sleep disturbance and impacts quality of life and functioning. Some interventions target circadian entrainment through modifying light exposure, but existing reviews of light interventions for sleep improvement include few studies in psychiatric populations. We examined effect of light interventions on sleep quality, duration and timing, and effect moderators. We included controlled studies in intrinsic circadian rhythm disorders (such as advanced or delayed sleep) and in neuropsychiatric disorders with assumed high prevalence of circadian dysregulation (such as affective and psychotic disorders). Articles were identified through database searching: 40 studies reporting 49 relevant intervention comparisons met inclusion criteria. Meta-analysis showed improvements in sleep continuity (ES = -0.23, p = 0.000), self-reported sleep disturbance (ES = -0.32, p = 0.014), and advancement of delayed sleep timing (ES = -0.34, p = 0.010). Although the small number of studies limited meta-regression, evening light avoidance was associated with greater increase in total sleep time. Effects of light on sleep and circadian outcomes have received limited attention in studies in psychiatric disorders, but results were promising in these groups. These findings invite further refinement and testing of light interventions to improve sleep in psychiatric disorders, with improved assessment and specification of problems, and the development and implementation of light schedule interventions for delayed sleep.

Inpatient phase-advance therapy for delayed sleep-wake phase disorder: a retrospective study.

PURPOSE: The efficacy of inpatient phase-advance therapy among patients with delayed sleep-wake phase disorder (DSWPD) has not been adequately investigated because response rates are considered low. We aimed to examine the efficacy of such treatment in this patient population. PATIENTS AND METHODS: The present retrospective study included data from 66 patients with DSWPD who had been admitted to Akita University Hospital for inpatient phase-advance therapy between September 1, 2005, and April 30, 2018. DSWPD was diagnosed based on the International Classification of Sleep Disorders, 3rd edition, criteria using electronic medical records. We examined remission rates during inpatient therapy as well as relapse rates at the time of the first outpatient examination following discharge. Univariate analysis was performed to investigate predictive factors for postinpatient therapy relapse. RESULTS: The rate of DSWPD remission over the course of inpatient phase-advance therapy was 100% (95% CI: 95.6%-100%), with a median duration of 1 day (IQR: 1-2 days; range: 1-9 days) until remission. The rate of relapse following discharge was 45.8% (95% CI: 32.7%-59.2%). Univariate analysis indicated that the rate of relapse was significantly higher for minors (under 18) than adults (18 and over), for those whose age at onset was below 16 years than for those whose age at onset was 16 or above, and for those with relatively low motivation for their occupation (P=0.0339, P=0.0136, and P<0.001, respectively). CONCLUSION: The rate of DSWPD remission under inpatient phase-advance therapy was remarkably high (100%), while the rate of relapse after discharge was ~50%. Further studies are required to determine the long-term prognosis of inpatient therapy, risk factors for relapse, and the types of treatment most effective for preventing relapse.

Circadian Rhythm Sleep-Wake Disorders in Older Adults.

The timing, duration, and consolidation of sleep result from the interaction of the circadian timing system with a sleep-wake homeostatic process. When aligned and functioning optimally, this allows wakefulness throughout the day and a long consolidated sleep episode at night. Mismatch between the desired timing of sleep and the ability to fall and remain asleep is a hallmark of the circadian rhythm sleep-wake disorders. This article discusses changes in circadian regulation of sleep with aging; how age influences the prevalence, diagnosis, and treatment of circadian rhythm sleep-wake disorders; and how neurologic diseases in older patients affect circadian rhythms and sleep.

Non-24-Hour Sleep-Wake Disorder Revisited - A Case Study.

The human sleep-wake cycle is governed by two major factors: a homeostatic hourglass process (process S), which rises linearly during the day, and a circadian process C, which determines the timing of sleep in a ~24-h rhythm in accordance to the external light-dark (LD) cycle. While both individual processes are fairly well characterized, the exact nature of their interaction remains unclear. The circadian rhythm is generated by the suprachiasmatic nucleus ("master clock") of the anterior hypothalamus, through cell-autonomous feedback loops of DNA transcription and translation. While the phase length (tau) of the cycle is relatively stable and genetically determined, the phase of the clock is reset by external stimuli ("zeitgebers"), the most important being the LD cycle. Misalignments of the internal rhythm with the LD cycle can lead to various somatic complaints and to the development of circadian rhythm sleep disorders (CRSD). Non-24-hour sleep-wake disorders (N24HSWD) is a CRSD affecting up to 50% of totally blind patients and characterized by the inability to maintain a stable entrainment of the typically long circadian rhythm (tau > 24.5 h) to the LD cycle. The disease is rare in sighted individuals and the pathophysiology less well understood. Here, we present the case of a 40-year-old sighted male, who developed a misalignment of the internal clock with the external LD cycle following the treatment for Hodgkin's lymphoma (ABVD regimen, four cycles and AVD regimen, four cycles). A thorough clinical assessment, including actigraphy, melatonin profiles and polysomnography led to the diagnosis of non-24-hour sleep-wake disorders (N24HSWD) with a free-running rhythm of tau = 25.27 h. A therapeutic intervention with bright light therapy (30 min, 10,000 lux) in the morning and melatonin administration (0.5-0.75 mg) in the evening failed to entrain the free-running rhythm, although a longer treatment duration and more intense therapy might have been successful. The sudden onset and close timely connection led us to hypothesize that the chemotherapy might have caused a mutation of the molecular clock components leading to the observed elongation of the circadian period.

The etiology of delayed sleep phase disorder.

According to classification manuals for sleep disorders, nine disorders are directly related to biological clock timing misalignments. Of all, delayed sleep phase disorder (DSPD) is the most commonly diagnosed, predominantly affecting adolescents, young adults, and insomnia patients. It is a persistent inability to fall asleep at earlier, more desirable and socially conventional times, coupled with extreme difficulty awakening in the morning. Considerable evidence shows a delay in the circadian clock to be associated with DSPD. Therefore, treatments have mainly focused on advancing the biological clock and sleep timing through pharmacotherapy, phototherapy and behavioral therapies. The clinical evidence indicates that these treatments are efficacious, at least in the short term. However, follow up studies show frequent patient relapse, leading researchers to speculate that alternative etiologies may be contributing to sleep and circadian clock delays in DSPD. The aim of the present paper is to review and collate current literature related to DSPD etiology in order to outline gaps in current knowledge and suggest future research.

The effects of light therapy on sleep problems: A systematic review and meta-analysis.

Although bright light therapy seems a promising treatment for sleep problems, research shows inconclusive results. This meta-analysis is the first to systematically review the effect of light therapy on sleep problems in general and on specific types of sleep problems in particular (circadian rhythm sleep disorders, insomnia, sleep problems related to Alzheimer's disease and dementia). Fifty-three studies with a total of 1154 participants were included. Overall effects and effects on separate circadian and sleep outcomes were examined. We calculated Hedges' g effect sizes and we investigated the effects of twelve moderators (design-related, treatment-related, participant-related). Light therapy was found effective in the treatment of sleep problems in general (g = 0.39), and for circadian rhythm sleep disorders (g = 0.41), insomnia (g = 0.47), and sleep problems related to Alzheimer's disease/dementia (g = 0.30) specifically. For circadian rhythm sleep disorders, effects were smaller for randomised controlled trials. For insomnia, we found larger effects for studies using a higher light intensity, and for sleep problems related to Alzheimer's disease/dementia larger effects were found for studies with more female participants. There was indication of publication bias. To conclude, light therapy is effective for sleep problems in general, particularly for circadian outcomes and insomnia symptoms. However, most effect sizes are small to medium.

Why the dim light melatonin onset (DLMO) should be measured before treatment of patients with circadian rhythm sleep disorders.

Treatment of circadian rhythm sleep disorders (CRSD) may include light therapy, chronotherapy and melatonin. Exogenous melatonin is increasingly being used in patients with insomnia or CRSD. Although pharmacopoeias and the European food safety authority (EFSA) recommend administering melatonin 1-2 h before desired bedtime, several studies have shown that melatonin is not always effective if administered according to that recommendation. Crucial for optimal treatment of CRSD, melatonin and other treatments should be administered at a time related to individual circadian timing (typically assessed using the dim light melatonin onset (DLMO)). If not administered according to the individual patient's circadian timing, melatonin and other treatments may not only be ineffective, they may even result in contrary effects. Endogenous melatonin levels can be measured reliably in saliva collected at the patient's home. A clinically reliably DLMO can be calculated using a fixed threshold. Diary and polysomnographic sleep-onset time do not reliably predict DLMO or circadian timing in patients with CRSD. Knowing the patient's individual circadian timing by assessing DLMO can improve diagnosis and treatment of CRSD with melatonin as well as other therapies such as light or chronotherapy, and optimizing treatment timing will shorten the time required to achieve results.