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Sleep is a noncontroversial foundation of health.

While this wiki offers good information, this subject and it's importance for APOE ε4s is much more extensive than what is presented here. Until this page can be expanded, refer to this "Found my Fitness" link Dr. Matthew Walker on Sleep for Enhancing Learning, Creativity, Immunity, and Glymphatic System. It offers a wealth of information on sleep and how it affects Alzheimer's including APOE ε4s. For anyone unfamiliar, Found my Fitness is Dr Rhonda Patrick's website where she explores many health issues, including many issues of concern to APOE ε4s since she is a carrier herself. If you're the type of person who doesn't like to sit in front of their computer to watch a video, you can also read the transcript of her interviews. Once you've opened the page, near the top of page you should see four links: Summary, Timeline, Glossary and Transcript.

But sleep is particularly critical for anyone at risk for AD, especially E4s (1,2). Here's what we know.

Why it is important for ApoE4s

  • The glymphatic system drains interstitial fluid from the brain during sleep, removing extra-cellular amyloid beta twice as fast during sleep as when awake. (3,4)
  • The release of melatonin at night also protects the brain by providing activity against oxidative and nitrosative stress-induced damage.
  • Sleep deprivation also increases plaque formation and Aβ aggregation further disrupts the sleep-wake cycle and diurnal fluctuation of Aβ, becoming a vicious cycle.
  • Sleep apnea has been shown to increase phosphorylated tau in mouse studies and microvascular problems in humans. (5)
  • Depression is another cause of disrupted sleep that should be treated to improve sleep and quality of life. (6)
  • Improving your sleep will pay off in other areas, too, such as reducing inflammation and improving insulin sensitivity. (7)

Strategies for better sleep

  • Dr. Bredesen recommends at least 7 hours of sleep each night (preferably 8). Bredesen also suggests going to bed before midnight at the latest to also maintain normal circadian rhythm. He notes that taking melatonin before bed can be helpful (0.5 to 1 mg). If awakening in the middle of the night, short term use of tryptophan (500 mg) at bedtime can help. Some people take 5-HTP instead of tryptophan, for a short while (not recommended for long-term use) for good results.
  • Turn off the TV, laptops, smartphones at least one or two hours before bed. Blue light coming from the screens at night disrupts the normal circadian release of melatonin. Some people on the forum use blue light blocking glasses at night and install programs such as f.lux on their computers to reduce the amount of blue light reaching the brain.
  • Rule out sleep apnea and treat if necessary.
  • Increased exercise can also improve sleep outcomes.
  • Don't eat within two-three hours of going to bed. Increased insulin level from eating exerts an inhibitory effect on the pineal gland and melatonin release. (8)
  • And finally, treat depression.

A deeper dive into the science

1) Sleep, Cognitive impairment and Alzheimer's disease: A systematic review and meta-analysis. (2016)

2) Evidence of association between sleep quality and APOE ε4 in healthy older adults: A pilot study. (2016)

3) Does selection for short sleep duration explain human vulnerability to Alzheimer's disease? (2017)

4) Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation (2016)

5) Association of Obstructive Sleep Apnea with Episodic Memory and Cerebral Microvascular Pathology: A Preliminary Study. (2016)

6) The role of depression in the insomnia of people with subjective memory impairment, mild cognitive impairment, and dementia in a community sample of elderly individuals in South Korea. (2016)

7) Associations between actigraphy-assessed sleep, inflammatory markers, and insulin resistance in the Midlife Development in the United States (MIDUS) study. (2016)

8) Melatonin and Pancreatic Islets: Interrelationships between Melatonin, Insulin and Glucagon (2013)

9) Circadian Rhythm Sleep Disorders. (2020)