It is the start of the new academic year, and you decide you want to hit the ground running by attending every lecture, completing every assignment on the day it is assigned, and following an extensive study schedule for every exam or essay. Come week five, however, you realize that sometimes skipping lectures and maybe not paying attention to your homework has left you with no idea on how to start your final project due in 24 hours. You thus grab a Red Bull and pull the most stressful all-nighter of your life to get this essay done, submitting it just in time. While you may feel relieved to have turned in your paper on time, your body may not feel the same way, especially if this is a regular occurrence. In fact, your wayward studying habits have just increased your likelihood for developing early-onset Alzheimer’s disease.
Exploring the Types of Sleep
The correlation between a poor sleep schedule and neurodegenerative disease can be explained by exploring the components of a typical sleep cycle. In sleep architecture, or the basic cyclical structure in a sleep pattern, there are two forms of sleep: non-rapid eye-movement (NREM) and rapid eye-movement (REM). Both types of sleep occur at different sleep stages, with different brain wave patterns and impact on other organs. A single sleep period lasts around 90 minutes and contains four stages: NREM stage 1 (N1), NREM stage 2 (N2), NREM stage 3 (N3), and REM.
Sleep begins with a brief N1, taking up 5% of total sleep time. Between one to seven minutes of sleep, breathing rate is regular and skeletal muscles remain at their normal stiffness. After transitioning into N2, heart rate and body temperature drop and special brain waves called K-complexes fire to maintain the sleep state and potentially consolidate memory. N2 initially lasts around 25 minutes, but lengthens with each successive cycle until it makes up around 45% of total sleep. In N3, the deepest non-REM sleep occurs. It is most difficult to rouse from this stage, with individuals remaining asleep even after hearing noises above 100 decibels. For context, a bulldozer or a motorcycle makes noise at the 100-120 decibel range. If awoken from this stage, individuals experience mental fogginess called sleep inertia. This disorientation temporarily impairs cognitive abilities for about 30 minutes to an hour. If the individual continues to sleep during this stage, however, the body spends this time repairing and regrowing tissues, bones, and muscles. Additionally, the slowing of metabolic processes during this stage provides the immune system with more energy to combat infections. After this stage, which takes up around 25% of total sleep, the REM stage occurs. While the skeletal muscles are relaxed, breathing becomes irregular. The brain increases its activity and oxygen intake at this stage, while pulse and blood pressure increase to variable amounts.
Upon conclusion of the REM stage, a new sleep period begins with N1. These cycles perpetuate as an individual remains asleep, but cease once receptors in the eye sense light. This stimulus travels down the optic nerve to a region of the brain called the hypothalamus, which releases hormones like cortisol that trigger the body to wake up.
How are the Glymphatic System and Sleep Deprivation Related?
But how do sleep cycles relate to Alzheimer’s? These concepts are linked through a recently-discovered network of neural cells on the surface of the brain called the glymphatic system. This system serves as both a waste elimination and a distribution method for essential compounds like lipids and neurotransmitters for the central nervous system, or the brain and spinal cord. Observations of this system’s behavior in mice over a 24-hour period revealed that the glymphatic system primarily operates during sleep and drastically decreases its function by up to 90% during wakefulness.
This system’s function is most optimal during the N3 sleep stage; as slower brain waves are emitted, cerebral blood volume decreases. This remaining space is replaced by cerebral spinal fluid (CSF), a protective liquid that rhythmically washes over the brain and spinal cord. It is this consistent washing that allows the glymphatic system to erode and dispel abnormal peptide buildup within the brain. With this relationship in mind, it becomes increasingly clear why it would be difficult to filter the same amount of toxins when hours of sleep are frequently shortened. Amyloid beta is one peptide that deteriorates neural function. One theory on this neurotoxin’s function suggests that it forms holes in the membrane of neurons, which disrupt the regulated exchange of materials along the membrane, causing cell death. Then, amyloid beta fragments adhere to the degenerating neuron to form a plaque. As these amyloid beta fragments continue to damage neurons, they decrease in synaptic activity, or communication across neurons. Eventually, the accumulation of indestructible protein amalgamations, like amyloid beta, lead to neurocognitive decline, a characteristic associated with the development of neurodegenerative diseases like Alzheimer’s and Parkinson’s.
Given that fewer hours of sleep means the glymphatic system has less time to dispel waste, the possibility of amyloid plaques forming increases with every hour of sleep lost. This inverse relationship–along with the facts that no cure exists for abnormal protein aggregation and that N3 becomes more difficult to achieve with older age–makes one thing very clear: if we want a better quality of life in the long term, we have to take sleeping seriously.
What can you do about this?
What can you do if you have pulled one-too-many all-nighters? To start, maintaining an organized schedule to sleep at least seven hours a night appears essential for a healthy lifestyle, according to Dr. Rebecca Robbins of Harvard Medical School and Brigham and Women’s Hospital. In their five-year study which tracked the risk for dementia (a broad set of conditions characterized by impaired cognitive reasoning and remembering abilities) in middle-aged adults aged 50 to 65, Robbins and her team found a statistically significant relationship between sleeping fewer hours a night and developing dementia. Specifically, sleeping fewer than five hours a night was correlated with a doubled risk for incident dementia.Worse yet, a 2015 study from Northwestern University comparing amyloid beta presence in the brains of adults across age demographics found substantial protein aggregate in individuals as young as 20. Those with existing cognitive impairments or at genetic risk for late-onset Alzheimer’s disease (diagnosis at 65 and up) should especially consider receiving seven to eight hours of sleep daily, as data collected by Dr. Eric Reiman and others from the Banner Alzheimer’s Institute have noted a distinct overproduction of an amyloid beta subtype in these groups.
In addition to observing a relationship between low hours of sleep and dementia, Robbins et. al also noticed a 45% increase in risk for dementia when individuals regularly took longer than 30 minutes to fall asleep. Dr. Suzanne Bertisch, a contributing author to Harvard Health Publishing, suggests waking up at the same time every day and reducing blue-light exposure to help regulate the body’s circadian rhythms. Maintenance of circadian rhythms are integral as they control the mental, physical, and biological changes the body will experience in a 24-hour-period. In the daytime, neuroscientist and physical therapist Dr. Joyce Gomes-Osman emphasizes the impact of regular aerobic and anaerobic exercise. By partaking in activities like running, cycling, yoga, or weight training for at least 2.5 hours per week, you can see holistic benefits in your body, such as increased heart, lung, and blood capacity, as well as increased neural blood vessels and brain volume. Not only can you fortify your muscles and bones, but you can also help your cognitive abilities by giving your neurons a chance to thrive.
And yet, the biggest takeaway is to recognize when you need a break. Pushing yourself when you feel overwhelmed just to complete tasks can be stress relieving in isolated situations, but it is easy to overlook the dire impact of long-term self-neglect (like early-onset Alzheimer’s) when the blinders are constantly on. As the new academic year comes into full swing, be sure to take care of yourself mentally and physically. In time, you could become the version of yourself the future you will thank.
Resources:
- https://www.ncbi.nlm.nih.gov/books/NBK526132/
- https://www.ncbi.nlm.nih.gov/books/NBK19956/#:~:text=There%20are%20two%20types%20of,eye%20movements%2C%20and%20muscle%20tone.
- https://www.hopkinsmedicine.org/health/conditions-and-diseases/sleepwake-cycles#:~:text=Your%20body%27s%20internal%20clock%20is,eyes%20senses%20the%20morning%20light.
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636982/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698404/
- https://www.sciencedirect.com/science/article/abs/pii/S2468867319301609
- https://www.news-medical.net/health/What-are-Amyloid-Plaques.aspx
- https://www.health.harvard.edu/blog/sleep-well-and-reduce-your-risk-of-dementia-and-death-2021050322508
- https://www.nih.gov/news-events/nih-research-matters/lack-sleep-middle-age-may-increase-dementia-risk
- https://academic.oup.com/brain/article/138/6/1722/2847057#supplementary-data
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4181671/
- https://www.aging-us.com/article/202591/text
- https://www.health.harvard.edu/blog/no-more-counting-sheep-proven-behaviors-to-help-you-sleep-2018110515313
- https://www.health.harvard.edu/blog/what-kinds-of-exercise-are-good-for-brain-health-2018050213762
- https://hearing.health.mil/Prevention/Causes-of-Injury/High-Decibel-Levels#:~:text=Levels%20and%20sources%20of%20damaging,a%20hammer%20pounding%20a%20nail
- https://www.bu.edu/articles/2019/cerebrospinal-fluid-washing-in-brain-during-sleep/
- https://nigms.nih.gov/education/fact-sheets/Pages/circadian-rhythms.aspx#:~:text=%E2%80%8B%E2%80%8BWhat%20are%20circadian,the%20study%20of%20circadian%20rhythms.
- https://unsplash.com/photos/woman-laying-on-bed-CwIU33KGToc