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Sleep needs change over the course of life. In normal aging, sleep usually becomes shorter and more fragmented, with older people often having multiple naps during the day. However, this type of sleep may not be the same in patients with Alzheimer's disease or other neurodegenerative conditions.
Lack of sleep and beta-amyloid
Recent studies have shown that lack of sleep, even for one night, can dramatically increase levels of beta-amyloid in the brain – one of the major toxic proteins associated with Alzheimer's disease.
During sleep, the brain uses its own glymphatic system (the brain's drainage system) to eliminate excessive levels of beta-amyloid and other accumulating metabolites. This clearance rate is doubled during sleep compared to the waking state and is accelerated by the largest interstitial space in the brain during sleep. However, during insomnia and lack of sleep (even a night), the brain is not able to effectively eliminate the levels of beta-amyloid and can therefore accumulate with the weather.
Proteolytic processing of beta-amyloid precursor protein. Image credit: Ilusmedical / Shutterstock
In addition, elevations of beta-amyloid have been shown to be accentuated in areas damaged at the beginning of Alzheimer's pathology, such as the hippocampus and thalamus (involved in memory, for example). The most sleep-deprived individuals (who had the highest increases in beta-amyloid in the thalamus) also had a poorer mood.
Some chronic sleep disorders can also increase the risk of Alzheimer's disease. Obstructive sleep apnea (OSA) is a major risk factor for dementia, both vascular dementia and Alzheimer's disease. The majority of patients with OSA are generally overweight and obese and may be risk factors common to both OSA and Alzheimer's disease. However, studies have shown a marked increase in beta-amyloid levels in the brains of OSA patients compared to those without this disease, despite being overweight.
Sleep deprivation early in life may therefore be a significant risk factor in the development of Alzheimer's disease later in life. Therefore, people with insomnia should see a doctor as soon as possible to delay or reduce the amyloid burden in the brain.
Sleep disorders in Alzheimer's disease
Most patients with Alzheimer's disease develop sleep problems that worsen as the disease progresses. Commonly observed sleep disorders in Alzheimer's patients include:
- Loss of ability to stay asleep despite being able to sleep
- Increased sleep latency (the time required to fall asleep is longer)
- Increased agitation before bedtime and all night
- Disorientation upon waking (in the night or in the morning)
- Sleepy during the day and alert at night (circadian abnormalities)
- Periodic limb movements (PLM) are aggravated in approximately 50% of patients with Alzheimer's disease.
- A shorter duration of slow wave sleep (SWS) and fast eye movement (REM) sleep despite the total number of sleep cycles remaining unchanged
It is important to note that not all large-scale studies have shown a significant correlation between sleep disturbance and Alzheimer's disease, either in the preclinical stage or after the onset of symptoms. Therefore, not all patients with Alzheimer's disease suffer from sleep problems. Similarly, not all people with sleep disorders in the elderly necessarily have Alzheimer's disease. However, many studies have shown that the capacity and quality of sleep are effectively disrupted in many cases of Alzheimer's compared to healthy controls of the same age.
It is now increasingly recognized that sleep loss can be a significant risk factor and symptom of Alzheimer's disease. However, it remains to be determined whether sleep loss contributes to the progression of Alzheimer's disease or causes sleep problems.
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