Alzheimer’s & Sleep
The quality and quantity of our sleep is crucial for cognitive processes including consolidating short-term memory. Cognitive impairments and sleep disturbances are often associated with certain conditions, including Alzheimer’s. In fact, sleep disturbances often precede the diagnosis and may even appear before any cognitive decline (1). One study found that people with high sleep fragmentation (repeated waking in the night) have 50% greater risk of developing Alzheimer’s six years later. Also, both mid- and late-life insomnia are associated with a higher dementia risk (1). Interestingly, the brain structures affected by disturbed sleep coincide with vulnerable areas in Alzheimer’s, indicating that sleep disturbances may exacerbate Alzheimer’s pathology. On the other hand, improving sleep may help to slow down its progression. It has been proposed that sleep disturbance be used to predict Alzheimer’s risk, and even be utilised as a disease biomarker (1).
Sleep stages can be divided into two groups: rapid eye movement (REM) and non-REM sleep. Non-REM sleep then can be divided into light and deep sleep. Deep sleep is also called slow wave sleep (1). The brain oscillates between these phases throughout the night. Within non-REM sleep, the cycling facilitates consolidaton processes that help to form long-term memories. REM sleep is thought to assist processing of emotional memories, as well as other forms of memory. After the age of sixty, sleep cycles become shorter and fewer, leading to less time spent sleeping overall as well as less REM and deep sleep. This means light sleep becomes dominant, leading to greater sleep fragmentation (1).
Sleep and Alzheimer’s
In Part One we learned about the hallmarks of Alzheimer’s: abnormal proteins or peptides called amyloid beta and phosphorylated tau. It turns out that sleep deprivation has been shown to increase both. This has been seen after only one night of poor sleep in cognitively normal people! It was particularly reduced or fragmented slow wave (deep) sleep that led to these Alzheimer’s hallmarks both not being cleared properly from the day or being produced in the night (1). Interestingly, those with Alzheimer’s accumulate plaques in brain areas that generate this slow wave sleep, and those with higher plaque levels also had worse performance on hippocampal-dependent memory, which deep sleep helps to consolidate. This highlights the importance specifically of deep sleep for Alzheimer’s prevention (1).
However, it is possible that a two-way relationship exists between sleep and plaques. Once amyloid plaques accumulate, more sleep alteration occurs, and non-REM sleep oscillations that allow deep sleep are hindered (1). This causes a vicious cycle between sleep and amyloid deposition that perpetuates the Alzheimer’s cascade.
Recently a system has been discovered in the brain which is involved in the removal of potentially toxic waste products produced through neural metabolism. This has been coined the “glymphatic system” and it turns out that it functions best during deep sleep (1). Studies have shown that this system can clear amyloid and tau out of the brain, making it a key potential player in Alzheimer’s prevention and a clear link between restorative sleep and Alzheimer’s.
You may also remember from Part One, that the key drivers of Alzheimer’s are glucose and lipid dysregulation, oxidative stress, and inflammation. Brain insulin resistance, the pancreatic hormone that regulates glucose, is a key feature of Alzheimer’s - so much so that Alzheimer’s has been coined “Type 3 diabetes”. You can learn more about insulin and diabetes in my previous blog series here. Sleep loss impairs insulin sensitivity - the responsiveness of cells to the presence of insulin (2). In fact, just one night’s sleep under four hours significantly increases blood glucose levels and lowers insulin sensitivity. The good news: restoring normal sleep time is associated with improved insulin sensitivity. Ultimately, hyperglycaemia (high blood sugar) ensues as glucose cannot move from the blood into cells, leading to the formation of advanced glycation end products, which damage tissue and cause inflammation (2). Increased levels of free fatty acids in the blood is also seen with sleep restriction, and may be the initiator of the inflammation and insulin resistance cascade (2).
Lack of sleep even affects the blood brain barrier - the protective mechanism that prevents certain substances from entering the brain (2). The blood brain barrier is selectively permeable - it only allows certain things in and out. Poor sleep causes “hyper-permeability” and things that shouldn’t be able to enter the brain are able to get through. This causes inflammation and oxidative stress, as well as a build up of amyloid beta plaques (2).
Optimising Sleep
There are several things that we can do in our day-to-day to improve the quality and quantity of our sleep. Here are some things you might like to be mindful of and try incorporating into your lifestyle to help you achieve 7-8 hours of quality sleep!
Diet and Meal Timing
A study performed in a hospital setting that measured how people ate without any restriction found that high intakes of saturated fat and sugar and low dietary fibre were associated with lighter and less restorative sleep (3). Consumption of carbohydrate-rich foods like starchy vegetables and whole grains decreases sleep latency (time taken to fall asleep) through enhanced production of serotonin, a sleep-regulating hormone (3). Higher consumption of the amino acid tryptophan in the evening has been shown to improve sleep in those experiencing disturbances (3). Foods high in tryptophan include whole grains, nuts and seeds. Sleep disorders have also been shown to be improved with supplementation of magnesium, zinc and vitamin D (3).
Caffeine is the most commonly consumed psycho-stimulant in the world (4). Caffeine consumption later in the day impacts our sleep. Caffeine has been shown to reduce the onset of drowsiness, therefore making sleep difficult, and it even affects our sleep stages (5). Interestingly, caffeine disrupts the production of the main metabolite of melatonin - the sleep regulating hormone mentioned earlier (5). Caffeine is primarily metabolised in the liver, specifically by an enzyme called CYP1A2 (6). These enzymes metabolise several chemicals within the body. However, there is significant inter-individual variation in the efficiency that we can process caffeine - a staggering five- to fifteen-fold difference in fact! (6). This explains why some people are more sensitive to coffee and other caffeine-containing products than others, with some needing to avoid it completely due to side effects like jitteriness and mild anxiety. If you know you are more sensitive, avoid having caffeine after 1pm to give yourself ample time to metabolise it before winding down for bed.
When we eat (in addition to what we eat) is now beginning to receive attention in the health space, including sleep. Our blood sugar, or glucose, regulation can impact our sleep quality. Our body is not very good at regulating blood sugar at night - we become more insulin resistant (9). To learn more about insulin resistance check out my blog here. This means that energy (specifically sugar and fats) cannot be processed well at night time, and this can impact our sleep. Some people are more susceptible than others, especially those who are more sedentary.
The saying “breakfast like a king, lunch like a prince and dinner like a pauper” turns out to play out quite right in the science of chronobiology! So try shifting most of your energy intake to earlier in the day, and avoid heavy and processed foods in the evening, and see if your sleep improves!
Exercise
While more studies are needed, there is a clear benefit of exercise on sleep. Exercise has been shown to increase sleep duration, reduce light sleep and promote REM sleep, sleep continuity, and sleep efficiency (7). Other researchers concluded that exercise promotes sleep quality rather than sleep duration.
However, exercise timing is important. Exercise earlier rather than later in the day may improve sleep, due to the stimulation of the sympathetic nervous system (“fight or flight”). This was specifically related to cardiovascular exercise, whereas resistance training timing does not seem to impair sleep (7). Morning exercise has been associated with reduced time to fall asleep, while evening exercise was found to reduce waking in the night. Additionally, the greater perceived exertion reported during exercise led to deeper sleep (7).
A study observing chronic rather than acute exercise effects over 15 weeks observed something different. They found that those who were of a healthy weight had better sleep quality than those who were over weight, and that introduction of exercise did not have an impact on sleep unless participants lost weight over the study period (7). While clearly more information is needed, it is clear that exercise can improve sleep - whether directly in an acute manner, or long-term with improvements in body composition.
Lights, Your Circadian Rhythm & Sleep
Humans (and other mammals) have a central master-clock in our brain called the suprachiasmic nuclei (SCN). The most important aspect of our life that sets and affects this clock is ambient light in the environment (8). The SCN also impacts the pineal gland in the brain, which is where melatonin (the sleep-facilitating hormone) is produced.
Exposure to daylight has been shown to increase sleep duration and quality, especially early morning light (8). In fact, exposure to early morning daylight has even been shown to have an anti-depressive effect. On the other hand, those with later light exposure had more sleep fragmentation and experienced less sleep (8). It is suggested that we go outside in the early morning to get a good dose of early morning light to assist us with our sleep.
Our modern-day exposure to artificial light, especially in the evenings, is also a cause for concern. Artificial light, especially LED lights, have been shown to impact our circadian clock and our sleep quality, partly by interfering with melatonin production (8). This is especially problematic at night-time when we are more sensitive to light exposure. Even bright devices like smart phones and e-readers have been found to negatively impact sleep, especially when they are used in the hours before bed (8). It is suggested that in the evening lights should be dimmed where possible, devices either avoided and/or set to a warm and low-light setting, and even blue light blocking glasses worn. These strategies will assist in reducing artificial light interference with our sleep physiology.
Your Sleep Spa
You can optimise your home and your night routine to get the most out of your sleep. It is important that your bedroom be dark, quiet and cool when you get into bed. This will help you to fall and stay asleep. It has been shown that heating in the hours leading up to bedtime can also aid sleep, including falling asleep, and deeper sleep. While your body is preparing for sleep it cools down, so it has been suggested that warming the body several hours prior in a bath, shower or sauna, may help the body cool down at bedtime. In fact, this cooling process has been linked to melatonin production (10).
Avoid using your bed for things like working, watching TV, and eating. This will help you to disassociate being in bed with activities where the brain is more active, and reduce the occurrence of pre-sleep over-thinking!
I hope you find these tips useful and that you can apply them to your life to improve your sleep hygiene and quality - not just for your brain health but for your overall health! Sleep is such a crucial aspect of our wellbeing and disease risk, so let’s do what we can to make sure we get a good night’s sleep!
Written by Jessica Zabow
Clinical Nutritionist (BHSc)
& Yoga Teacher (RYT500)
References:
Lloret, M-A., Cervera-Ferri, A., Nepomuceno, M., Monllor, P., Esteve, D., & Lloret, A. (2020). Is sleep disruption a cause of consequence of Alzheimer’s disease? Reviewing its possible role as a biomarker. International Journal of Molecular Sciences, 21(3), 1-19. https://doi.org/10.3390/ijms21031168
Garcia-Aviles, J.E., Mendez-Hernandez, R., Guzman-Ruiz, M.A., Cruz, M., Guerrero-Vargas, N.N., Velazquez-Moctezuma, J., & Hurtado-Alvarado, G. (2021). Metabolic disturbances induced by sleep restriction as potential triggers for Alzheimer’s disease. Frontiers in Integrative Neuroscience, 15(722523), 1-13. https://doi.org/10.3389/fnint.2021.722523
Frank, S., Gonzalez, K., Lee-Ang, L., Young, M.C., Tamez, M., & Mattei, J. (2017). Diet and sleep physiology: Public health and clinical implications. Frontiers in Neurology, 8(393), 1-9. https://doi.org/10.3389/fneur.2017.00393
Banks, N.F., Tomko, P.M., Colquhoun, R.J., Muddle, T.W.D., Emerson, S.R., & Jenkins, N.D.M. (2019). Genetic polymorphisms in ADORA2A and CYP1A2 influence caffeine’s effect on postprandial glycaemia. Scientific Reports, 9(10532), 1-9. https://doi.org/10.1038/s41598-019-46931-0
O’Callaghan, F., Muurlink, O., & Reid, N. (2018). Effects of caffeine on sleep quality and daytime functioning. Risk Management and Healthcare Policy, 11(1), 263-271. https://doi.org/10.2147/RMHP.S156404
Urry, E, Jetter, A., Landolt, H-P. (2016). Assessment of CYP1A2 enzyme activity in relation to type-2 diabetes and habitual caffeine intake. Nutrition and Metabolism, 13(1), 1-9. https://doi.org/10.1186/s12986-016-0126-6
Dolezal, B.A., Neufeld, E.V., Boland, D.M., Martine, J.L., & Cooper, C.B. (2017). Interrelationship between sleep and exercise. Advances in Preventive Medicine, 2017(1), 1-14. https://doi.org/10.1155/2017/1364387
Blume, C., Garbazza, C., & Spitschan, M. (2019). Effects of light on human circadian rhythms, sleep and mood. Somnologie, 23(3), 147-156. https://doi.org/10.1007/s11818-019-00215-x
Malin, S.K. (2021). Timing is everything, right? Meal impact on circadian related health. The Journal of Clinical Endocrinology and Metabolism, 106(2), e1050-e1051. https://doi.org/10.1210/clinem/dgaa533
Harding, E.C., Franks, N.P., & Wisden, W. (2019). The temperature dependence of sleep. Frontiers in Neuroscience, 13(1), 1-16. https://doi.org/10.3389/fnins.2019.00336