Sleep Biomarkers and Alzheimer's Disease Risk

New study shows sleep biomarkers may be predictive of future Alzheimer's risk.

Posted Dec 02, 2020

 Image Point Fr/ Shutterstock
Electroencephalography (EEG) polysomnography can be used to assess changes in slow-wave sleep patterns as a predictor of cortical amyloid-beta (Aβ) deposition
Source: Image Point Fr/ Shutterstock

Insufficient sleep is a public health issue, with an estimated 50-70 million adults in the U.S. having a sleep-related disorder. According to the CDC's Vital Health Survey studying the behaviors of 76,669 adults, nearly 30% report sleeping less than 6 hours per day.2 The long-term consequences of insufficient sleep not only impact our brain's operational capacity but also increase the risk for other health problems, including obesity, diabetes, cardiovascular disease, hypertension, stroke, anxiety, depression, and dementia

Getting restful sleep is essential to memory and cognition and protects the brain from age-related cognitive decline. When we sleep, several restorative processes occur in the brain, including (i) the consolidation of memories from short-term into long-term storage,3 (ii) the clearance of metabolic waste,4 (iii) and emotional processing, which helps to stabilize mood.5

Studies show that the change in quality and quantity of sleep as we age may increase our risk of Alzheimer's disease.6,7 The production and deposition of the amyloid-beta (Aβ) peptide, which can accumulate and form toxic plaques around neurons in the brain, is one of the primary pathological hallmarks implicated in Alzheimer's.  Given that Aβ deposition occurs decades before the symptoms of cognitive decline, it serves as a preclinical marker for Alzheimer's disease risk and progression.  

Higher accumulation of amyloid-beta (Aβ) after one night of sleep deprivation

A 2018 study published in PNAS by Dr. Eshan Shokri-Kojori and colleagues measured Aβ levels in the living human brain in 20 healthy controls at baseline and after one night of sleep deprivation using positron emission tomography (PET) imaging with a radiotracer that binds to amyloid protein (18F-Florbetaben).6 They demonstrate that Aβ levels increase after only one night of sleep deprivation, particularly in regions of the brain associated with memory and mood (i.e., hippocampus and thalamus).   This finding is important as the hippocampus shows some of the earliest structural and functional changes in Alzheimer's disease.  When we sleep, protein clearance occurs through a combination of the glymphatic system (a network of vessels in the brain that helps clear waste) and the gamma oscillations during slow-wave sleep.   

Sleep study reveals biomarkers associated with amyloid-beta (Aβ) accumulation in cognitively healthy older adults

As we age, changes in our sleep patterns can lead to increases in Aβ accumulation. A study published in the November issue of Current Biology by Joseph R. Winer and colleagues found that impairments in sleep physiology are associated with a high rate of Aβ accumulation in the human brain.7 

In this study, the authors hypothesize that the speed of Aβ plaque deposition may be regulated by the level of impaired sleep, which they assess by measuring brain wave activity using electroencephalogram (EEG) polysomnography. Thirty-two cognitively healthy older adults from the Berkeley Aging Cohort Study underwent a sleep study and repeated PET imaging (11C-PiB) to reveal the rate of Aβ accumulation over an average of 3.7 years (± 2.4 yr.).  They discovered certain features of human sleep are predictors of the rate of Aβ accumulation in healthy older adults.  Specifically, non-rapid eye movement slow-wave activity below 1 Hz and sleep efficiency were the best predictors of cortical Aβ deposition over time.  Why is this finding important?  The ability to detect these slow-wave sleep changes with EEG polysomnography may become an easily accessible, non-invasive measure for assessing preclinical Alzheimer's disease, which can be validated using PET imaging. These findings are encouraging as early detection provides an opportunity to start lifestyle and therapeutic interventions at a time when they can effectively slow disease progression.

Sleep is a modifiable risk factor for preventing cognitive decline

We have all had sleepless nights, from the all-nighters in college to being a new parent. Those in occupations requiring shiftwork, including healthcare professionals, firefighters, police officers, military personnel, and employees in the transportation and hospitality industries are routinely impacted by circadian rhythm disruptions.  As we look to the future, sleep studies may offer measurable biomarkers that help to assess the risk of cognitive decline.  For now, we can use this information to take inspired action to treat insomnia or improve our sleep hygiene habits to support our long-term brain health.  Here are a few practical strategies to improve sleep:

  1. Cognitive-behavioral therapy (CBT). CBT has a robust evidence base for effectively treating insomnia and other sleep-related disorders.  It combines cognitive therapy and strategies to improve sleep habits, which have better long-term outcomes than pharmacotherapy.8
  2. Regular physical activity. Physical activity is one of the best nonpharmacological treatments for insomnia, with randomized controlled trials showing improvements in sleep quality, sleep time, and sleep efficiency.  It also increases blood flow to the brain, improves learning and memory, increases hippocampal volume, and animal studies demonstrate exercise reduces Aβ plaque deposition.9
  3. Avoid caffeine a minimum of 6 hours before bed (i.e., coffee, chocolate, caffeinated energy drinks). Caffeine has been shown to produce disruptive effects on sleep, reducing sleep efficiency, prolonging sleep latency, and reducing total sleep time.  A study published in the J of Clin Sleep Med revealed that caffeine's effects on sleep were present even when consumed 6 hours before bedtime.10
  4. Reduce evening light exposure 3 hours before bed. Light gives us a cue for synchronizing our circadian rhythms. Light exposure at inappropriate times, even from our smartphones, televisions, and computers, can disturb circadian rhythms, affecting melatonin levels.  Melatonin is the hormone produced by the pineal gland which regulates our sleep-wake cycle.  Elevated levels of melatonin facilitate sleep. Artificial room light (300-500 lux) suppresses melatonin, while dimmer light environments will help to support melatonin secretion.   If you are curious about the lux levels in your room, you can download an app with a lux meter on your smartphone.
  5. Keep the bedroom cool. The thermal environment we are in plays an essential role in regulating sleep.  Given that non-REM sleep cycles are accompanied by a temperature decline that cools your body and brain, setting the thermostat between 60 and 67° F can help induce sleep.


1. Medicine Io. Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem. Washington, DC: The National Academies Press; 2006.

2. Schoenborn CA, Adams PF, Peregoy JA. Health behaviors of adults: United States, 2008-2010. Vital Health Stat 10 2013:1-184.

3. Buzsaki G. Memory consolidation during sleep: a neurophysiological perspective. J Sleep Res 1998;7 Suppl 1:17-23.

4. Jessen NA, Munk AS, Lundgaard I, Nedergaard M. The Glymphatic System: A Beginner's Guide. Neurochem Res 2015;40:2583-99.

5. Walker MP, van der Helm E. Overnight therapy? The role of sleep in emotional brain processing. Psychol Bull 2009;135:731-48.

6. Shokri-Kojori E, Wang GJ, Wiers CE, et al. beta-Amyloid accumulation in the human brain after one night of sleep deprivation. Proc Natl Acad Sci U S A 2018;115:4483-8.

7. Winer JR, Mander BA, Kumar S, et al. Sleep Disturbance Forecasts beta-Amyloid Accumulation across Subsequent Years. Curr Biol 2020;30:4291-8 e3.

8. Park KM, Kim TH, Kim WJ, An SK, Namkoong K, Lee E. Cognitive Behavioral Therapy for Insomnia Reduces Hypnotic Prescriptions. Psychiatry Investig 2018;15:499-504.

9. Ebrahimi K, Majdi A, Baghaiee B, Hosseini SH, Sadigh-Eteghad S. Physical activity and beta-amyloid pathology in Alzheimer's disease: A sound mind in a sound body. EXCLI J 2017;16:959-72.

10. Drake C, Roehrs T, Shambroom J, Roth T. Caffeine effects on sleep taken 0, 3, or 6 hours before going to bed. J Clin Sleep Med 2013;9:1195-200.