The Link Between Poor Sleep and Alzheimer’s Disease
Professor Dale Bredesen is a Professor of Neurology who has spent his life working in the field of Alzheimer’s research. He has developed The Bredesen Protocol™ which, in his book entitled “The End of Alzheimer’s”, he claims has helped reverse the symptoms of diagnosed Alzheimer’s or ‘mild cognitive impairment’ in over 90 % of 140 patients.
Professor Bredesen is respected around the world for his work within the fields of neurological disease and brain decline, having written more than 200 peer reviewed papers and with a range of independent studies examining specific aspects of Professor Bredesen’s program including sleep, diet and exercise – with each one showing a marked benefit to brain health.
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This article looks at the significance of sleep for brain health, and ways to ensure that an individual receives the eight hours of sleep recommended by Professor Bredesen.
Research undertaken at Washington Medical School and Stanford University has shown that not getting a good night’s sleep can result in an increase in amyloid-beta (Aβ) - a molecule which is associated with Alzheimer’s disease (AD) - within the cerebrospinal fluid, therefore giving further support to the connection between poor sleep and Alzheimer’s disease.
A range of other studies have suggested a link between AD and sleep, though it was previously unclear whether or not disturbed, poor sleep was a cause or an effect of AD pathology. This study however gives clear evidence that issues with sleep are a causal factor for the onset of dementia and AD.
One sleepless night is not likely to have much effect as Aβ levels will return to normal following a good night’s sleep, though people who have chronic sleep issues such as sleep apnoea or insomnia do run a higher risk of developing AD:
Additionally, the study showed that the participants who had slept poorly for a whole week had a higher accumulation of the protein tau. Tau is a regular cellular protein, but this can become hyperphosphorylated and aggregate – another part of AD’s pathology.
Tau aggregate build-up can contribute towards neurofibrillary tangles which can form within neurons, adversely affecting their function. It is believed that abnormal tau generally accumulates within the brain regions involved with memory.
Amyloid-Beta and Tau
Being a multifactorial condition, Alzheimer’s disease has many contributory factors. Extracellular amyloid plaques and intracellular neurofibrillary tau tangles were the first defined histopathologic features of AD and in the Alzheimer’s brain, abnormal amounts of naturally occurring amyloid-beta clump together, forming plaques which collect between neurons, disrupting communication and cell function.
The neurofibrillary tangles are actually abnormal accumulations of the protein tau that collect inside neurons. Within healthy neurons, tau’s role is to bind to and stabilize microtubules – internal structures that guide nutrients from the cell body to the dendrites and axon.
However, with Alzheimer’s disease, abnormal chemical changes (hyperphosphorylation) mean that tau aggregates in an insoluble form eventually forming into tangles inside neurons. These tangles hinder the neuron’s internal transport system, harming communication between neurons.
Physiology of Sleep
Generally, an individual’s sleep cycle will move through 5 different stages, with each one being essential in ensuring quality sleep. Each of these stages must be moved through appropriately.
Stage 1: Transition Phase
This phase usually lasts up to 10 minutes and sometimes involves a sense of falling. This is non-REM sleep.
Stage 2: Light Sleep
This phase will generally last between 5 and 15 minutes. The sleeping person may experience fragments of dreams. The eyes might roll slowly from side to side as heart rate and breathing slow, and blood pressure reduces.
Stage 3 and 4: Moderate Deep Sleep
This non-rapid eye movement (NREM) sleep phase is a period of moderately deep sleep. It is often referred to as slow wave sleep or deep sleep. Here, heart rate slows down, blood pressure drops, and breathing becomes even slower. This stage of sleep is the restorative stage where regeneration and tissue repair occur.
Stage 5: REM (Rapid Eye Movement)
REM sleep occurs for 10 minutes in the first cycle, then up to an hour in later cycles. REM sleep is the stage of the sleep cycle where most dreaming occurs, and this stage is believed to be vitally important for cognitive development as well as mental health and wellbeing. Children are likely to spend much more time in REM sleep than adults. After REM sleep, the body will return to Stage 2 sleep.
An average person will cycle through these sleep stages around 4 or 5 times a night. The REM stage is generally entered about 90 minutes after falling asleep and while the first cycle of REM sleep may only be brief, subsequent cycles will become longer with REM sleep lasting up to an hour as sleep progresses. Quality sleep means following a day and/or night (diurnal) cycle of activity and alertness during the day followed by rest and sleep at night.
The Vicious Cycle of Poor Sleep and Alzheimer’s Disease
While this particular study supports the notion that disturbed sleep can increase the risk of AD, additional evidence exists to suggest that amyloid deposition, the decreased cognitive and physical function associated with AD and damage to the sleep/wake areas of the brain can also contribute to poor sleep. These links create a cycle of poor sleep, additional amyloid deposition, reduced activity and damage which only makes the problem worse.
“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
While it may seem to be common sense that sleep has a central role in the protection of individuals’ cognitive health, the way that sleep protects peoples’ brain is not, as yet, fully understood. There are several mechanisms which may underpin the reciprocal relationship between AD pathology/behavior and the sleep-wake cycle:
- The reduction of pro-inflammatory cytokines – neuro-inflammation is a driver of dementia
- Removal of toxic proteins from the interstitial space while sleeping
- Glial-mediated circadian clearance of soluble Aβ, for example, amyloid-beta is cleared during sleep
- Reduced neuronal activity during slow-wave sleep, for example, slow-wave sleep allows neurons to ‘rest’ and therefore recuperate and repair
- Deficits in resting state functional connectivity, for example, new connections between neurons are formed as the brain rests
How Do We Sleep?
As the day progresses, most people are exposed to daylight and it is during this time that the brain produces the ‘feel good’ neurotransmitter serotonin. As the sun goes down, the brain’s pineal gland recognizes the resulting reduction in light, signaling the conversion of serotonin to melatonin – a hormone responsible for instigating sleep.
The circadian rhythm is also managed by the relationship between cortisol and melatonin. Cortisol is a hormone released during periods of stress, but it is also vital for the maintenance of the sleep/wake cycle.
Cortisol is required to wake up, so it is higher in the morning, dropping during the day and reaching its lowest level in the evening at which point, the need to sleep will likely be highest. Additionally, cortisol inhibits melatonin, so it must drop in the evening in order for sleep to happen.
During periods of stress, cortisol levels can still be high into the evening, thus considerably and adversely affecting the ability to fall asleep. Stress can cause people to feel tired all day then wake up in the evening, leading them to suffer from poor sleep which can make the stress worse.
Insulin is released following the consumption of carbohydrates, and this can also inhibit melatonin. Due to this, it is highly recommended not to eat a large meal three hours before going to bed.
Melatonin is not only vital for healthy sleep, but it also possesses properties that can help maintain good cognitive health. Melatonin has been shown to:
- Help regulate antioxidant defense systems
- Inhibit the formation of tau tangles
- Promote Brain Derived Neurotrophic Factor (BDNF) for the development of new healthy neurons
- Aid in the reversal of inflammatory processes
- Help with the breakdown of beta-amyloid plaque
- Protect brain mitochondria from free radicals
GABA is another important neurotransmitter, and this particular one is the primary inhibitory transmitter of the central nervous system (CNS) and is therefore responsible for calm and relaxation. It is a well-established fact that the activation of GABA receptors favors sleep and it has also been shown that individuals suffering from insomnia have lower levels of GABA. Because of this, some anti-anxiety medications and sleeping pills function by increasing the levels of GABA.
Sleep Hygiene
Sleep hygiene is a means of preparing the body for sleep. Just having a routine every day can really help to program the body into knowing when it is time to sleep, though different techniques will work better for different people, so it is important to look at this on an individual, case-by-case basis. Examples of techniques that can be used to promote good sleep hygiene include:
- Stopping smoking
- Ensuring full light exposure for a period during the day in order to help maintain a proper circadian rhythm
- Eating no less than three hours before bedtime
- Avoiding alcohol before bedtime
- Maintaining good nutrition
- Having low color-temperature fluorescent or LED bulbs of 3,000 kelvin or below (daylight is 6,500 kelvin)
- Meditation/mindfulness exercises
- Sleep in darkness and quiet using, for example, black out blinds, eye masks and earplugs
- Having the same bedtime and waking up time every day
- Use of aromatherapy – for example, lavender oil on the pillow or in the bath
- Avoiding too many liquids in the evening
- Exercising regularly, but avoiding intense exercise after dinner
- Avoiding screens such as the TV, phone or computers for at least thirty minutes before bed. Apps are available that can block the blue light which inhibits melatonin production – these include Twilight for Android; Nightshift for IOS and F.Lux for PC
- Cutting down on caffeine
- Using Epsom salt baths to aid muscle relaxation
- Ensuring the use of a comfortable mattress and pillow
Nutrients should also be considered when seeking to promote a healthy sleep pattern. Particular nutrients are involved in the creation of the neurotransmitters needed for sleep. Examples of nutrients that are used include:
- 5HTP – the precursor to serotonin, converted in the presence of magnesium and vitamin B6. Tryptophan is the amino acid precursor to 5HTP and is also found in bananas, walnuts, almonds, turkey and salmon.
- Fiber from prebiotic foods - which provide food for bacteria within the gut and recent studies have confirmed that the balance of these microflora has an effect on sleep quality.
- Vitamins B6, B12, folate and magnesium – these contribute to the functioning of the nervous system and normal psychological function
- Live bacteria – an imbalance of gut flora (referred to as dysbiosis) may be associated with poor sleep.
References are available on request.
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Last updated: Sep 4, 2018 at 7:11 AM
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