Why Poor Sleep May Be Linked to Alzheimer’s

February 22, 2022

The amyloid plaques that build up in the brains of those with Alzheimer’s disease may result in part from disrupted sleep, according to a new report. The study found that interruption of our circadian rhythms, the roughly 24-hour daily cycle that regulates our sleep and wakefulness, may interfere with the ability of immune cells in the brain to clear the proteins that clump together to form these plaques. The study involved mouse cells, but it builds on earlier research showing the importance for people of sound sleep in maintaining brain health. 

“A healthy sleep pattern might be important to alleviate some of the symptoms in Alzheimer’s disease,” said study author Jennifer Hurley, an expert in circadian rhythms at Rensselaer Polytechnic Institute. Developing therapies that could readjust or recalibrate our daily circadian rhythms, which tend to drift as we age, could lead to new approaches to treating Alzheimer’s, she said.  

Our circadian rhythms control a range of body processes, including hormone levels, body temperature and range of additional biological processes. Poor sleep and disruption of these circadian rhythms have long been recognized as a feature of Alzheimer’s disease. People with Alzheimer’s often have trouble sleeping at night and often catch up with sleep throughout the day. Poor sleep may precede the onset of the disease by years. In addition, those with Alzheimer’s often become increasingly confused and agitated beginning at dusk, and they may pace and become disoriented throughout the night, a process sometimes referred to as “sundowning.” 

For the study, published in PLOS Genetics, researchers focused on cells in the brain called microglia, which are immune system cells that seek out, ingest and destroy unwanted material like beta-amyloid, the toxic protein pieces that stick to each other to form amyloid plaques. Microglia are found in both mice and people, and their function is believed to be highly conserved in all mammals. 

In lab studies, the researchers found that these microglia cells appeared to follow a circadian rhythm, with greater activity occurring times when we (or the mice) would normally sleep. The findings suggest that during a sound and uninterrupted night of sleep, the microglia appear to become activated and clear the toxic beta-amyloid from the brain. But disruptions of normal sleep interfere with this process, causing beta-amyloid to build up in the brain. As beta-amyloid accumulates, it clumps together to form the insoluble plaques that are a hallmark of Alzheimer’s disease. 

The findings build on earlier research showing how sound, restorative sleep may help gird the brain against the ravages of Alzheimer’s disease. Healthy older adults who sleep soundly tend to have less buildup of beta-amyloid in the brain. Deep sleep appears to act as a kind of cleaning system, ridding the brain of toxic debris. Other studies have shown that men and women who slept less than six hours a night in their 50s and 60s were at increased risk of developing dementia when they were older. 

Similarly, sleep apnea, a common nighttime disorder in which people stop breathing for short periods, hundreds of times during the night, has been linked to memory decline and dementia. Sleep apnea may be particularly prevalent in people with Alzheimer’s disease. 

Sleep problems generally increase with advancing age and, as these and other studies show, may be priming the brain for dementia. While many people turn to sleeping pills, these drugs they are not known to respect our natural sleep architecture, which alternates between five stages of sleep during each sleep cycle. Insomnia medications also do not fully induce deep sleep, and may in fact interfere with our natural circadian rhythms. Indeed, the long-term use of some sleeping pills has been tied to an increased risk of Alzheimer’s and other forms of dementia. 

Experts recommend various tips for improving sleep quality, among them: 

  • Consider psychological approaches like cognitive behavioral therapy, or CBT, which teaches people to challenge negative thoughts at bedtime with positive thoughts that induce relaxation. Experts recommend CBT, rather than drugs, as the first-line treatment for sleep problems.  
  • Avoid coffee and other caffeine-rich beverages after 3 p.m. Avoid alcohol in the hours before bedtime. 
  • Practice good sleep hygiene. Try to keep a consistent sleep schedule, going to bed around the same time each night. Keep the bed a place to sleep, rather than watching TV. 
  • Avoid phones and computers tablets near bedtime. The light they emit can interfere with circadian rhythms. 
  • Until more effective treatments or a cure for Alzheimer’s disease are found, getting better quality sleep may be one more way to help slow the onset of dementia as the years advance. 

By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by Marc Flajolet, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University. 

Source: Clark GT, Yu Y, Urban CA, Fu G, Wang C, Zhang F, et al. “ Circadian control of heparan sulfate levels times phagocytosis of amyloid beta aggregates” PLoS Genetetics, February 10, 2022  


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