Abstract
Sleep disturbance is a common symptom in patients with various neurodegenerative diseases, including Alzheimer’s disease (AD), and it can manifest in the early stages of the disease. Impaired sleep in patients with AD has been attributed to AD pathology that affects brain regions regulating the sleep–wake or circadian rhythm. However, recent epidemiological and experimental studies have demonstrated an association between impaired sleep and an increased risk of AD. These studies have led to the idea of a bidirectional relationship between AD and impaired sleep; in addition to the conventional concept that impaired sleep is a consequence of AD pathology, various evidence strongly suggests that impaired sleep is a risk factor for the initiation and progression of AD. Despite this recent progress, much remains to be elucidated in order to establish the benefit of therapeutic interventions against impaired sleep to prevent or alleviate the disease course of AD. In this review, we provide an overview of previous studies that have linked AD and sleep. We then highlight the studies that have tested the causal relationship between impaired sleep and AD and will discuss the molecular and cellular mechanisms underlying this link. We also propose future works that will aid the development of a novel disease-modifying therapy and prevention of AD via targeting impaired sleep through non-pharmacological and pharmacological interventions.
Highlights
Sleep disturbance is a common symptom associated with Alzheimer’s disease (AD), which is the leading cause of dementia worldwide [1]
Contrary to the conventional understanding that impaired sleep in patients with AD is a consequence of AD-related pathology, multiple recent epidemiological studies have suggested that sleep disturbance could be a risk factor for cognitive decline and AD
Both epidemiological and experimental studies have led to the recent concept of a bidirectional relationship between AD and impaired sleep (Figure 1)
Summary
Sleep disturbance is a common symptom associated with Alzheimer’s disease (AD), which is the leading cause of dementia worldwide [1]. More than 60% of patients with AD develop sleep disturbance, which often occurs at the early stages of the disease or even before the onset of major cognitive decline [2] Impaired sleep in these patients has been attributed to the progression of AD pathology to brain regions that regulate the sleep–wake or circadian rhythm (Figure 1) [3]. Multiple studies using animal models of AD have indicated that impaired sleep exacerbates memory decline and AD-related pathology (Figure 1) [4] These recent findings suggest that sleep disturbance is a potential modifiable risk factor for AD and could be a novel target for disease-modifying therapies to prevent the development of AD and/or ameliorate the cognitive decline in patients with AD [3].
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