Clinical management of sleep disturbances in Alzheimer's disease: current and emerging strategies

Abstract

Sleep and circadian disorders in Alzheimer’s disease (AD) are more frequent than in the general population and appear early in the course of the disease. Quality of sleep and quality of life are parallel in these patients, and such disorders also represent a heavy burden for caregivers. Although alterations in melatonin and hypocretins (orexins) seem to play a key role in the origin of these disturbances, the etiology of these disorders is multifactorial, including many factors such as environment, behavior, treatments, and comorbidities, among others. A comprehensive evaluation of sleep in each patient is essential in the design of the treatment that includes nonpharmacological and pharmacological approaches. One particularly interesting point is the possibility of a role of sleep disorders in the pathogenesis of AD, raising the possibility that treating the sleep disorder may alter the course of the disease. In this review, we present an update on the role of sleep disorders in AD, the bidirectional influence of sleep problems and AD, and treatment options. Behavioral measures, bright light therapy (BLT), melatonin, and other drugs are likely well known and correctly managed by the physicians in charge of these patients. In spite of the multiple treatments used, evidence of efficacy is scarce and more randomized double-blind placebo-controlled studies are needed. Future directions for treatment are the establishment of BLT protocols and the development of drugs with new mechanisms of action, especially hypocretin receptor antagonists, melatonin receptor agonists, and molecules that modulate the circadian clock.

Pre‐ to post‐inpatient treatment of subjective sleep quality in 5,481 patients with mental disorders: A longitudinal analysis

“…Furthermore, insomnia and symptoms of insomnia have been linked to comorbid medical diseases (Akbaraly et al., ) as well as neurological and mental disorders (Urrestarazu & Iriarte, ). Especially in patients suffering from depression, insomnia is highly prevalent and may be prodromal to depression and as well constitute an independent risk factor for the occurrence of depressive episodes (Baglioni et al., ).…”

Evaluation of the efficacy of randomized controlled trials of sensory stimulation interventions for sleeping disturbances in patients with dementia: a systematic review

“…Specifically, 44% of patients with dementia (PwD) suffer from sleeping disturbances 3. Sleeping problem is a very vital problem not only for the patient but also for the caregiver.…”

“…However, the effect of melatonin itself on treating sleeping disorders in dementia needs further research. Additionally, the impact of cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) seems limited 3. Likewise, it is also a common phenomenon to use sedative–hypnotics and second-generation antipsychotics in order to treat sleeping disorders in dementia 12.…”

The hidden variables problem in Alzheimer's disease clinical trial design

“…noted that elevated Aβ may lead to the fragmentation of nonrapid eye movement sleep [24]. Moreover, they and others found that lack of nonrapid eye movement sleep can also lead to the elevation of Aβ aggregation [23,24]. Investigations have further observed that clearance of Aβ may be compromised when sleep is diminished [25].…”

“…Sleep disturbances are endemic among patients with dementia, and the magnitude of sleep pathology frequently parallels disease progression [23]. This association has recently been clarified with a potential mechanism when Mander et al noted that elevated Ab may lead to the fragmentation of nonrapid eye movement sleep [24].…”