Breaking the vicious cycle of poor sleep and Alzheimer’s disease

Yesterday saw the publication of Professor of Neurology, Dale Bredesen’s much anticipated book “The End of Alzheimer’s”. Professor Bredesen who has spent his life in Alzheimer’s research has developed The Bredesen Protocol™ with which he has, so far, reversed symptoms of diagnosed Alzheimer’s or ‘mild cognitive impairment’ in more than 90% of the 140 patients he has worked with. You can find out more and purchase your copy of the book here.

Professor Bredesen is a globally respected scientist in the field of brain decline and neurological disease and has over 200 peer reviewed papers. There are also a number of independent studies looking at single aspects of Professor Bredesen’s programme – diet, sleep, exercise etc. and each has shown benefit to brain health. In this week’s blog, we look at the importance of sleep for brain health and ways to ensure you get the 8 hours he recommends.

Recent research carried out at Stanford University and Washington Medical School has demonstrated that a poor night’s sleep can lead to an increase in amyloid-beta (Aβ), a molecule associated with Alzheimer’s disease (AD), within the cerebrospinal fluid, thereby supporting the connection between poor sleep and Alzheimer’s disease.

Many other studies have identified a link between sleep and AD, however it has been unclear whether disturbed or poor sleep was a cause or an effect of AD pathology. This study provides evidence that sleep problems are a causal factor for the onset of AD and dementia. Although one sleepless night will have little effect, as Aβ levels return to normal after a good night’s sleep, people with chronic sleep disturbances such as insomnia or sleep apnoea are at an increased risk of developing AD.

“The main concern is people who have chronic sleep problems, I think that may lead to chronically elevated amyloid levels, which animal studies have shown lead to increased risk of amyloid plaques and Alzheimer’s.” Professor Yo-El Ju, of Washington University.

The study also identified that participants who slept poorly for a whole week also had an increased accumulation of the protein tau. Tau is a normal cellular protein however it can become hyperphosphorylated and aggregate which is another part of the pathology of AD. The build-up of tau aggregates can contribute to neurofibrillary tangles which form within neurons and affect their function. It appears that abnormal tau accumulates in specific brain regions involved in memory.

Amyloid-beta and Tau

Alzheimer’s disease is a multifactorial condition with many contributory factors. The first defined histopathologic features of AD were extracellular amyloid plaques and intracellular neurofibrillary tau tangles. In the Alzheimer’s brain, abnormal levels of naturally occurring amyloid-beta clump together to form plaques that collect between neurons and disrupt cell function and communication.

Neurofibrillary tangles are abnormal accumulations of a protein called tau that collect inside neurons. In healthy neurons, tau normally binds to and stabilises microtubules (internal structures which guide nutrients from the cell body to the axon and dendrites).

In Alzheimer’s disease, however, abnormal chemical changes cause tau to detach from microtubules and stick to other tau molecules, forming threads that eventually join to form tangles inside neurons. These tangles block the neuron’s transport system, which harms synaptic communication.

Physiology of Sleep

When we sleep we cycle through 5 different stages each one appears to be important and quality of sleep relies on moving through each stage appropriately.

  • STAGE 1: TRANSITION PHASE –  normally lasts up to 10 minutes, sometimes a sense of falling, non-REM sleep
  • STAGE 2: LIGHT SLEEP –  lasts 5-15 mins. Fragments of dreams may be experienced, and the eyes may slowly roll from side to side, heart rate slows, blood pressure reduces, breathing slows
  • STAGE 3 and 4: MODERATE DEEP SLEEP (non-rapid eye movement, NREM) – is a period of moderately deep sleep. Known as slow wave sleep, or deep sleep, stage 4 is deeper. Heart rate slows, your blood pressure drops and your breathing becomes slower. This is the restorative stage, when tissue repairs and regeneration occurs
  • STAGE 5: REM (rapid eye movement) – (10 mins in first cycle, up to an hour in subsequent cycles). Most dreaming occurs in REM sleep. This stage is believed to be important for psychological health and well-being, also for cognitive development. Children spend much more time in REM sleep than adults. Once REM sleep is over, the body usually returns to stage 2 sleep

Sleep cycles through these stages approximately 4-5 times throughout the night. On average, we enter the REM stage approximately 90 minutes after falling asleep. The first cycle of REM sleep might last only a short amount of time, but each cycle becomes longer. REM sleep can last up to an hour as sleep progresses. Good quality sleep involves following a day and/or night (i.e. diurnal) pattern of alertness and activity during the day followed by quiescence at night.

Vicious cycle of poor sleep and AD

Although this study supports the idea that sleep disturbances increase the risk of AD, there is also certainly evidence that amyloid deposition, damage to the sleep/wake regions of the brain as well as decreased cognitive and physical function associated with AD can also contribute to poor sleep. This creates a vicious cycle of poor sleep and further amyloid deposition, damage and reduced activity therefore exacerbating the problem.

Although there is still some debate over this “chicken and egg” situation, when supporting patients with AD (or chronic sleep problems) it is a simpler intervention to improve sleep quality rather than to reduce Aβ, tau or brain injury. It is also important to be aware of the risk that chronic sleep deprivation can bring and therefore prioritise sleep support for individuals with sleep problems.

“Evidence from animal and human studies suggests that AD pathology itself, including the presence of amyloid plaques and tau tangles, disrupts the sleep–wake cycle. Evidence from animal and human studies also suggests that prolonged wakefulness may increase levels of soluble amyloid-β in the brain, and in turn, exacerbate AD pathology.” Lin et al.

Importance of sleep

It may seem quite obvious that sleep plays an essential role in protecting our cognitive health, however, how sleep protects our brains is not fully understood. Possible mechanisms underlying the reciprocal relationship between the sleep–wake cycle and AD pathology and behaviour include:

  • Decreased neuronal activity during slow-wave sleep i.e. slow wave sleep gives neurons a “rest” allowing them to repair and recuperate
  • Deficits in resting state functional connectivity, i.e. during rest new connections between neurons are formed
  • Glial-mediated circadian clearance of soluble Aβ, i.e. amyloid-beta is cleared during sleep
  • Clearance of toxic proteins from the interstitial space during sleep
  • Reduction of pro-inflammatory cytokines (neuro-inflammation is a driver of dementia)

“Efficient and effective sleep is more than just a luxury; it is critical for the proper function of many organ systems, particularly the brain.” Musiek et al 2015

How do we sleep?

Throughout the day we are exposed to day light and during this time the brain signals the production of serotonin (our “feel good” neurotransmitter). When the sun goes down the pineal gland within the brain recognises the reduction in light and signals the conversion of serotonin to melatonin. Melatonin is a neurotransmitter which is responsible for instigating sleep.

Our circadian rhythm is also governed by the relationship between melatonin and cortisol. Cortisol is a hormone which is essential for our sleep/wake cycle and is also released during periods of stress. Cortisol is important for waking us up, therefore it is high in the morning and begins to drop during the day to its lowest level in the evening which allows us to sleep. Cortisol inhibits melatonin, therefore this drop in the evening is essential for allowing sleep to occur.

When someone is undergoing a period of stress cortisol levels can remain high in the evening and therefore can significantly affect the ability to fall asleep. Many people who are stressed feel tired all day and then wake up in the evening and don’t want to go to bed, leading to poor sleep which can further exacerbate stress.

Insulin (released after carbohydrate consumption) can also inhibit melatonin, therefore it is recommended not to eat a large meal 3 hours before bedtime.

Not only is melatonin essential for sleep, it also possesses properties which protect cognitive health independently of its effect on sleep. Melatonin has been shown to:

  • Up regulate antioxidant defence systems
  • Help reverse inflammatory processes
  • Aid the breakdown of beta-amyloid plaque
  • Protect brain mitochondria from free radicals
  • Inhibit tau tangles from forming
  • Help promote Brain Derived Neurotrophic Factor (BDNF) for the development of new healthy neurons

Another important neurotransmitter is GABA, the main inhibitory neurotransmitter of the CNS which is therefore responsible for relaxation and calm. It is well established that activation of GABA receptors favours sleep. It has been shown that people who suffer from insomnia have lower levels of GABA and some sleeping pills and anti-anxiety medications work by increasing GABA.

Sleep Hygiene

Sleep hygiene is a way of preparing the body for sleep, having routines every evening can help programme the body to knowing when it is sleep time, different things can work for different people therefore it is important to work with the individual to see what suits their needs. Techniques that can help improve sleep are:

  • Have same bedtime and wake up time every day
  • Avoid screens (TV, phone, computers etc) 30 minutes before bed. Apps can block blue light (blue light inhibits melatonin production) – Twilight for android; Nightshift for IOS and F.Lux for PC
  • Sleep in darkness and quiet – black out blinds / eye masks / earplugs
  • Low colour-temperature fluorescent or LED bulbs 3000 Kelvin or below (daylight is 6500 Kelvin)
  • Ensure full light exposure for a period during the day, this helps maintain a proper circadian rhythm
  • Eat no less than 3 hours before bedtime
  • Avoid alcohol before bedtime
  • Cut down on caffeine
  • Avoid too many liquids in the evening
  • Quit Smoking
  • Exercise regularly. Avoid vigorous exercise after dinner
  • Aromatherapy – lavender oil on pillow or in bath
  • Meditation/mindfulness
  • Comfortable mattress and pillow
  • Epsom salt baths – aids muscle relaxation

Nutrition and sleep

It is important to consider nutrients, particularly those which are involved in the manufacture of key neurotransmitters that are necessary for sleep. Nutrients which can support sleep are:

Montmorency cherry – a natural source of melatonin, cherry juice or concentrated montmorency cherry supplements have been shown to improve sleep quality

Magnesium – aids muscle and nerve relaxation and is a cofactor for the enzyme which produces serotonin (which is then converted to melatonin)

B6 – cofactor for the production of serotonin and GABA

5HTP – precursor to serotonin, converted in the presence of magnesium and B6. Tryptophan the amino acid precursor to 5HTP is also found in walnuts, almonds, banana, turkey and salmon.

B12 – essential for normal psychological and cognitive function

Probiotics – a healthy balance of gut flora is associated with sleep, dysbiosis (imbalance of the microflora) is associated with poor sleep

Glutamine – an amino acid which is the precursor to the neurotransmitter GABA

FOS (fructo-oligosaccharides) – considered a prebiotic (food for live bacteria within the gut), recent studies have shown that the balance of the microflora have an effect on sleep quality. (90% of serotonin is produced in the gut)

Ashwagandha – an Ayurvedic adaptogenic herb which is associated with modulating the stress response and also aiding sleep, it also has been shown to increase the neurotransmitter GABA. Studies have also suggested that it plays a potential role in the clearance of amyloid beta

Action Against Alzheimer’s Programme

The Action Against Alzheimer’s progamme is a nutrition and lifestyle coaching programme, delivered by Cytoplan Licensed Nutritional Therapists. The programme aims to support brain health using the diet and lifestyle techniques that are being used by Professor Bredesen.

A series of weekly meetings cover topics that have been shown in research as important for brain health – nutrition, gut health, stress, sleep, exercise and brain training. The workshops are designed to help people engage with each aspect of the programme and understand what they need to do to optimise brain function. Thus the workshops include talks, activities and discussion to show how to make and sustain lifelong food and lifestyle choices to improve brain health.

To find out more please visit – www.action-against-alzheimers.co.uk


The End of Alzheimer’s by Professor Dale Bredesen offers a groundbreaking plan to prevent and reverse Alzheimer’s Disease, that fundamentally changes how we understand cognitive decline. You can find out more and purchase your copy of the book via this link.


If you have any questions regarding the topics that have been raised, or any other health matters please do contact me (Helen) by email at any time.

helen@cytoplan.co.uk

Helen Drake and the Cytoplan Editorial Team


Relevant Cytoplan products

Cytonight – Powder containing Montmorency cherry, glycine, magnesium and hops

Biofood Magnesium – An organic matrix form of magnesium, complete with natural amino acid carriers

5HTP Plus – source of 5HTP from the natural shrub Griffonia Simplicifolia, with added magnesium & vitamin B6

Fos-A-Dophilus – live bacteria supplement with additional FOS

Cytobiotic Active – 9 strains of live bacteria with the prebiotic inulin


Bibliography

Lim MM1, Gerstner JR, Holtzman DM The sleep-wake cycle and Alzheimer’s disease: what do we know? Neurodegener Dis Manag. 2014;4(5):351-62.

Peter-Derex L, Yammine P, Bastuji H, Croisile B. Sleep and Alzheimer’s disease. Sleep Med Rev. 2015 Feb;19:29-38. Epub 2014 Apr 3.

Musiek ES, Xiong DD, Holtzman DM Sleep, circadian rhythms, and the pathogenesis of Alzheimer disease. Exp Mol Med. 2015 Mar 13;47:148. 2014.121.

Yo-El S. Ju Sharon J. Ooms Courtney Sutphen Shannon L. Macauley Margaret A. Zangrilli Gina Jerome Anne M. Fagan Emmanuel Mignot John M. Zempel Jurgen A.H.R. Slow wave sleep disruption increases cerebrospinal fluid amyloid-β levels. Brain, Volume 140, Issue 8, 1 August 2017, Pages 2104–2111

The End of Alzheimer’s, Dale Bredesen, August 2017


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3 thoughts on “Breaking the vicious cycle of poor sleep and Alzheimer’s disease

  1. Very interesting research article indeed. Our 24/7 society is seemingly run on sleep deprivation which is an alarming thought when you consider the findings demonstrated by the article. Cortisol & the stress of modern living seem to be contributory factors to many problems; of which AD is one.
    My late Mother (d.aged 99) blamed her sleep problems on WW2 conscripted work at Leylands factory, where night work rotas were obligatory. The threat & stress of air raids & daily life in general at the time also contributed to her sleep problems. During WW2 my Father was with 14th Army in Burma at the time & she never knew whether her husband was alive or dead until VJDay. Mother sadly suffered from A.D. during the last 15 yrs of her life; causing the mental deterioration which contributed to her eventual demise.

  2. An interesting article. However, its credibility, in my opinion, is lessened by including data from animal research, which I consider irrelevant.

  3. Hi It is important to cut out completly caffeine even the caffeine in chocolate. I think it is esp important to do this in care homes where the people are given tea and coffee every few hours. No wonder they are awake and walking around like zombies all hours of the day and night. I know I cant handle caffeine at all now even in chocolate, can’t even take de caffe. Great there is a book out and hope more people get this message.

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