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Alzheimer's Sleep Patterns: Understanding Sleep-Wake Disturbances

February 3, 2023Neelem Sheikh

Alzheimer’s disease is often accompanied by a range of non-cognitive symptoms. Disturbances in sleep-wake cycles are a common and challenging symptom of Alzheimer’s disease. Research suggests that sleep disorders affect as many as 56% of people living with Alzheimer’s disease.

While it has long been known that Alzheimer’s disease causes changes in sleep patterns, the sleep-wake cycle has recently been implicated as a factor involved in Alzheimer’s disease development. Understanding the bidirectional relationship between sleep and Alzheimer's disease will be important for optimizing treatment and management approaches for people living with Alzheimer’s disease.

In this article, we will take a look into the intricacies of Alzheimer’s sleep patterns and discuss the potential mechanisms that underlie this relationship.

Alzheimer’s Sleep Patterns

Although sleep changes are generally more common in the later stages of Alzheimer’s disease, some studies have found that these changes occur very early in the disease continuum alongside the pathological changes (e.g. beta amyloid plaques).

The most common sleep-related changes reported by people living with Alzheimer’s disease include sleep fragmentation, insomnia, excessive daytime sleepiness, and sundowning, which refers to the emergence or increment of neuropsychiatric symptoms—such as confusion, agitation, anxiety, irritability, and disorientation—occurring in the late afternoon and early evening. Sundowning is believed to be due in part to the phase shifts in the normal circadian alertness profile that are observed in the advanced stages of Alzheimer’s disease.

Polysomnography studies (sleep studies) have revealed several common characteristics of Alzheimer’s sleep patterns. This includes:

  • Decreased slow-wave sleep
  • Decreased slow-wave activity
  • Decreased rapid eye movement (REM) sleep
  • Prolonged REM latency
  • Increased sleep fragmentation
  • Increased proportions of N1 and N2 non-REM sleep

Proposed Mechanisms 

A primary clinical feature of Alzheimer’s disease is progressive neurocognitive impairment. Research suggests that sleep-wake variables are strongly correlated with cognitive and functional measures. This suggests that as Alzheimer’s disease advances, sleep-wake patterns are disrupted in parallel with the decline in cognition and function. A similar relationship has been established between sleep-wake disruption and Alzheimer’s disease pathology (e.g., beta-amyloid plaques and tau tangles).

Throughout the disease course, beta-amyloid plaques and tau tangles form in multiple brain regions, several of which are essential for sleep-wake regulation. This includes the cerebral cortex, the locus coeruleus, the basal forebrain, and the hypothalamus. Consequently, it has been hypothesized that 1) Alzheimer’s disease pathology disrupts sleep and 2) disrupted sleep exacerbates Alzheimer’s pathology.

Another proposed mechanism that may be driving Alzheimer’s sleep patterns relates to slow-wave sleep and beta-amyloid deposition and clearance. Individuals living with Alzheimer’s disease experience reduced amounts of and/or disrupted slow-wave sleep. Reduced or disrupted slow-wave sleep may lead to a relative augmentation in neuronal activity that 1) increases the production of beta-amyloid and/or 2) reduces the effectiveness of beta-amyloid clearance. 

Methods for Improving Sleep in People Living with Alzheimer’s Disease

Sleep-wake disturbances are a common and often debilitating aspect of Alzheimer’s disease. However, a growing body of research implicates sleep-wake regulation as a potentially modifiable factor to delay Alzheimer’s disease progression. In other words, regulating sleep-wake cycles may not only improve sleep duration and quality of life but may have neurocognitive benefits as well.

Currently, non-pharmacological approaches are often the first line of defense for managing sleep disturbances in Alzheimer’s and other neurodegenerative diseases. Typically, this involves the use of sleep hygiene, which includes limiting alcohol and caffeine intake, getting sufficient daytime sunlight exposure, limiting daytime napping, sticking to a regular sleep schedule, exercising regularly, and avoiding exposure to light in the evening. 

Therapies and Medications for Improving Sleep

Emerging non-pharmacological therapies to improve Alzheimer’s sleep patterns include bright light therapy, acupressure, stimulus control therapy, meditation, cognitive behavioral therapy, and sleep restriction, among others. These non-pharmacological therapies represent promising interventions that pose little harm and may benefit individuals with Alzheimer’s disease with regard to sleep duration and, potentially, cognition and function. 

When non-pharmacological approaches are not sufficient, medications, such as tricyclic antidepressants (e.g., nortriptyline), sleeping pills (e.g., zolpidem and zaleplon), and benzodiazepines (e.g., lorazepam and oxazepam), may be used to treat sleep changes. In 2014, the FDA approved Belsomra, an orexin receptor antagonist, to manage insomnia in people with mild-to-moderate Alzheimer’s disease. There are, however, significant risks associated with using sleep-inducing medications in individuals with Alzheimer’s disease, including increased risk of falls and serious injury.

There is a clear need for further comprehensive clinical research to assess neurocognitive and pathological outcomes for both pharmacological and non-pharmacological therapies.

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