Introduction

Alzheimer's disease is the most common type of dementia, making up about two-thirds of dementia cases in people aged 65 and older.¹ Recently, several studies have shown that this condition is linked to sleep problems, such as less total sleep time, poor sleep quality and awakenings during sleep.^2,3

In this article, we will overview the symptoms and progression of Alzheimer's disease, dive into the main sleep disturbances, discuss their impact on the progression of the disease, understand the mechanisms linking sleep disorders and Alzheimer's disease and describe the interventions to manage sleep problems in these patients. 

Understanding Alzheimer's disease

Alzheimer's disease is characterised by abnormal formations called neuritic plaques and neurofibrillary tangles build up in the brain. Neuritic plaques are tiny spherical lesions made of a substance called amyloid beta-peptide, surrounded by swollen nerve endings. Neurofibrillary tangles are thread-like structures found inside neurons, made of a protein called tau.¹ With time, these changes can lead to neuronal cell death, which gradually affects the brain, causing progressive:¹

• Behavioural problems
• Memory loss
• Language difficulties
• Attention problems
• Comprehension impairments
• Reasoning difficulties
• Judgment issues

Alzheimer’s disease is the most common form of dementia in people over 65, but it's rarely observed before this age. There's no cure for this disease yet, but treatments can help manage symptoms.¹

Symptoms and progression

Symptoms of Alzheimer's disease vary depending on how far the disease has progressed. It can be divided into different stages, depending on the degree of cognitive impairment:¹

• Preclinical or presymptomatic in which people don't show any signs of Alzheimer's disease, but lab tests can confirm it. Certain proteins in the brain fluid can help detect it. However, these proteins aren't only found in Alzheimer's, so they're not always reliable. Nonetheless, a mix of factors, like certain genes, test scores, and brain scans, can help predict if someone will develop mild cognitive impairment

• Mild, when language problems, memory issues or problem-solving can appear. People in this stage can still do their daily activities and stay social, but about 10% might develop dementia each year. The risk of this happening depends on how severe their impairment is when diagnosed and other factors linked to the disease

• In the late stage of dementia, patients face serious memory problems. They might struggle to find the right words when speaking, make mistakes in what they say, speak less than usual, or talk around a word they can't remember. They might also have trouble with things like judging distances or putting things together properly. Around 20-40% of patients might start believing things that aren't true, and some might see, hear, or smell things that aren't there. Almost half of them might act out in disruptive ways. Their sleep patterns also change, becoming more fragmented

Impact on cognitive functions and daily life

Alzheimer's disease starts with memory problems, but it can get worse over time and people might experience other problems like feeling angry, anxious or depressed, having trouble sleeping, and thinking people are against them. As it progresses, they may need help with everyday tasks. Eventually, they might find it hard to walk, eat, or swallow. Some people might live for a few years after diagnosis, while others might live longer, but their quality of life is usually poor.¹

Sleep disturbances in Alzheimer's disease

Types of sleep disturbances associated with Alzheimer's disease

Sleep changes can start before people show signs of memory problems. People who are still in the early stage experience more interruptions in their sleep and wake cycles.²

People who are starting to have memory problems, a sign of Alzheimer's disease, tend to sleep differently. Studies have observed that people with Alzheimer's disease:^2,3

• Take longer to fall asleep
• Wake up more during the night 
• Have reductions of specific features of the light sleep stage N2
• Have less slow-wave sleep, also known as N3
• Take longer to enter REM sleep 
• Have less REM sleep
• Have less overall sleep time 
• Have worse sleep quality

Moreover, many Alzheimer's patients have trouble with their internal body clock, causing sleep issues. They may have trouble sleeping at night and end up napping a lot during the day. This happens because parts of the brain responsible for controlling sleep patterns change because of the disease.²

Impact of sleep disturbances on Alzheimer's disease progression 

In the past, it was believed that sleep problems and dementia were just part of normal ageing happening at the same time. But recent studies suggest that having sleep problems, especially in middle age, might increase the risk of developing Alzheimer's disease later in life.³ 

Deep sleep (slow wave sleep) helps with remembering facts, while REM sleep is important for emotional and procedural memories. When our deep sleep is disrupted, it can lead to an increase in beta-amyloid levels, associated with worsened learning, memory, attention, and decision-making abilities, which are all affected by Alzheimer's disease. Indeed, a study showed that reduced deep sleep and REM sleep were linked to lower scores on cognitive tests.²

Potential mechanisms linking sleep disorders and Alzheimer's disease

There are several potential mechanisms linking sleep disorders and Alzheimer's disease:^2,3

• Inflammation: Sleep disturbance has been associated with increased inflammation in the brain and could contribute to the buildup of harmful substances associated with this disease
• Effects of sleep on brain activity: sleep disruptions could lead to increased brain activity, which might contribute to the accumulation of proteins associated with the condition
• Brain cleaning system: our brains have a system that cleans out toxins, including those linked to Alzheimer's disease, while we sleep. Disrupted sleep might interfere with this cleaning process, allowing harmful substances to build up in the brain
• Circadian rhythm: problems with the body's internal clock might also play a role in the development of Alzheimer's disease. Disruptions in the sleep-wake cycle could affect learning, memory, and inflammation levels in the body
• Other consequences of sleep problems: disrupted sleep could also increase stress on brain cells, affect the brain's protective barriers, and reduce the formation of new brain cells, all of which could contribute to the development of the disease

Overall, understanding how sleep problems contribute to Alzheimer's disease could lead to new ways to prevent or slow down its progression.²

Diagnostic approaches

The best way to objectively check different aspects of sleep and investigate if you have sleep disturbances is by polysomnography,² which will record your brain waves, eye movements, muscle activity, heart rate, breathing, and oxygen levels.⁴ 

However, some studies have used a tool called the Neuropsychiatric Inventory, which has one question about sleep issues to check sleep in Alzheimer's patients. It asks about:⁵

• Waking up the caregiver at night 
• Waking up early
• Daytime napping 
• Rates how often it happens, how bad it is, and how upsetting it is

Management and treatment

Non-pharmacological interventions

One challenge with non-drug treatments for sleep problems is that they might not work for all Alzheimer's patients, especially if they have other health issues. Nonetheless, giving caregivers training and support can help them better manage sleep problems in these patients.⁵ Here are some tips to create a cosy environment and encourage sleep:⁶

• Stick to regular meal times and a consistent bedtime routine
• Keep the bedroom at a comfortable temperature
• Use nightlights and comforting objects for security
• Treat any pain that might be causing discomfort
• Let the patient get some sunlight exposure in the morning
• Encourage daily exercise, but avoid strenuous activities close to bedtime
• Avoid alcohol, caffeine, and smoking
• If the person is taking a medication that is a cholinesterase inhibitor (like tacrine, donepezil, rivastigmine, or galantamine), avoid giving it before bedtime
• If the person wakes up during the night, encourage them to get out of bed until they feel sleepy again and avoid watching TV during periods of wakefulness

Pharmacological interventions

Studies on how different medications affect sleep in Alzheimer's patients found some treatments showed promise, but there were mixed results and not enough data for many treatments:^5,6

• Sedative medications, like benzodiazepines and non-benzodiazepine 'z-drugs': some studies didn't find significant effects on sleep with these drugs, while others found improvements in sleep quality and daytime sleepiness with zolpidem
• Melatonin/melatonin receptor agonists: some studies stated melatonin did not improve sleep or agitation in Alzheimer's patients, but others saw improvements in sleep quality and less sundowning, i.e., changes in behaviour that occur around dusk. Melatonin also showed some improvement in cognition and daily activities
• Antidepressants: trazodone increased sleep duration and efficiency without increasing daytime sleepiness. However, mirtazapine, another antidepressant, didn't show significant effects on sleep in Alzheimer's patients
• Antipsychotics: low-dose risperidone improved sleep symptoms and decreased daytime wandering in Alzheimer's patients. It also helped with neuropsychiatric symptoms and caregiver mood, without accelerating mental decline or causing oversleeping
• Orexin receptor antagonists: this medication inhibits the action of orexin, a neurotransmitter involved in the sleep-wake cycle. Suvorexant increased total sleep time and reduced waking after sleep onset in Alzheimer's patients without worsening cognitive tests. It's the only medication approved specifically for treating insomnia in Alzheimer's patients

For those who need medication, it's best to start with a low dose and increase slowly. Sleep medicines can be risky for older people with cognitive issues because they can increase the chances of falling, confusion, and difficulty taking care of oneself. Antipsychotic drugs can raise the risk of stroke and death in older adults with dementia and therefore should be used carefully. Besides, pharmacological treatment for these problems is individually prescribed, doctors choose a medication based on the person's behaviour along with their sleep problems and goals for treatment may change as Alzheimer's progresses.⁶

Summary

Alzheimer's disease, the most common form of dementia, affects the brain progressively, leading to memory loss, behavioural changes, and difficulty with daily tasks.¹ Sleep problems, including disruptions in sleep patterns and changes in sleep quality, are common in Alzheimer's patients, often appearing before memory problems become noticeable. These sleep disturbances can worsen cognitive function and may even increase the risk of developing Alzheimer's disease or progression.

The relationship between sleep problems and Alzheimer's disease is complex, involving inflammation, disruptions in brain activity, impaired brain cleaning systems, and disturbances in the body's internal clock.

Management of sleep problems in Alzheimer's patients typically starts with non-drug interventions, including maintaining a consistent sleep schedule, promoting exposure to natural light, encouraging regular exercise, and avoiding stimulants like caffeine and alcohol. Caregivers play a crucial role in implementing these strategies.

When medication is necessary, it's essential to start with a low dose and proceed cautiously, as sleep medications and antipsychotics can have serious side effects in older adults with cognitive impairment. Different classes of drugs, including benzodiazepines, antidepressants, and orexin receptor antagonists, may be prescribed based on the individual's symptoms and goals of treatment. However, managing sleep problems in Alzheimer's patients requires a personalized approach that considers the patient's specific symptoms, preferences, and overall health status.