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How Sleep “Cleans” Your Brain and Fends Off Alzheimer’s Disease

Sleep: we spend nearly a third of our lives doing it, yet only recently have we begun to understand its true purpose. You’ve probably read countless articles about how getting enough sleep is important for preventing a variety of diseases, including diabetes, depression, and even Alzheimer’s. However, while strong correlations have existed for decades, until recently there was still little evidence to show why we sleep or how it fends off disease.

I’m currently writing this article from Switzerland, where I’m conducting research at the EPFL Brain Mind Institute over the summer. My research is on the connection between sleep deprivation and Alzheimer’s disease, so for me it’s especially important to help others understand why sleep is so important for your brain’s overall health. A few recent breakthroughs in sleep science research have revolutionized the field and brought about an exciting new era of neuroscience, particularly for Alzheimer’s disease research.

The Brain: A Dumping Ground for Neuronal Waste

While you’re awake, the 100 billion neurons in your brain are hard at work. Through an incredibly complex network of connections and signals, your neurons keep your heart pumping, your muscles moving, and your attention focused on the task at hand. Every time a neuron fires a signal, it undergoes a series of chemical reactions to produce neurotransmitters, which it uses to communicate with other cells. These reactions also produce waste byproducts that need to be disposed of. The neuron packages the waste into vesicles and excretes them into the fluid that surrounds cells in the brain. How these waste products were cleared from the fluid remained a mystery for a long time. More on that in a bit.

These waste products used to not be seen as particularly important to study. But in 2005, a group of scientists came up with a crazy idea that would end up shaking the foundations of Alzheimer’s research: what if amyloid-beta is one of these byproducts of neuronal activity? As a bit of background, amyloid-beta is a protein that forms sticky plaques in the brains of people with Alzheimer’s disease. At large enough sizes, these plaques become toxic to neurons, resulting in neurodegeneration. This is believed to be one of the main driving forces behind the development of Alzheimer’s disease. At the time, we  knew that amyloid-beta came from neurons, but were unsure what caused the neurons to produce it or how to stop them.

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This is what an amyloid-beta plaque looks like inside a real brain. Image Source

The researchers tested their hypothesis using mice genetically engineered to produce human amyloid-beta. They surgically implanted an electrode in the mice’s brains, which was used to measure the neurons’ activity levels. They also implanted a microdialysis probe, which sampled the mice’s brain fluid periodically to monitor levels of amyloid-beta. When the researchers electrically stimulated the mice’s brains, causing neurons to become highly active, they saw an abrupt increase in amyloid-beta levels in the area of stimulation. Conversely, when they used drugs to decrease neuronal activity, amyloid-beta levels dropped.

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This is one of the figures from that study. Panel A shoes the mice’s EEG activity (a measure of neuronal firing) before and after the electrical stimulation. Panel B shoes the immediate increase in amyloid-beta levels after stimulation, while Panel C shoes the decrease after drug treatment to reduce neuronal activity.

The results of this landmark study were published in the journal Neuron and have since been cited hundreds of times by other papers. Many other studies have confirmed the initial results and expanded into other model organisms. The revelation that amyloid-beta is excreted during neuronal activity was huge, because until then we’d assumed that only “diseased” neurons were releasing the toxic protein. This new research showed that not only were healthy neurons releasing amyloid-beta, but they did so every time they were activated.

Sleep: The Good Kind of “Brainwashing”

This brings us back to the question I brought up earlier: how does the brain get rid of all these waste products? If amyloid-beta and other toxic byproducts of neuronal activity were allowed to accumulate unchecked, we’d probably all develop Alzheimer’s disease in infancy. The brain must have some way of cleaning itself. We knew that the waste products eventually ended up being flushed into the cerebrospinal fluid, but no one was sure how exactly it got there from within the brain.

The answer finally came in 2012 with the discovery of the glymphatic system. Researchers found that cerebrospinal fluid was able to enter the brain through a cavity called the subarachnoid space, and flush out toxins via drainage vessels running parallel to the veins. They demonstrated that this pathway was capable of clearing away amyloid-beta from the brain in mice.

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The recently-discovered glymphatic system pumps cerebrospinal fluid through the subarachnoid space into the brain, where it flushes out toxins (including amyloid-beta) through vessels surrounding the veins. Image Source

Only a year later, another breakthrough came. A paper published in Science revealed that the glymphatic system was intricately linked with sleep. During sleep, the channels that carry fluid through your brain expand by 60%, resulting in enhanced glymphatic drainage. The researchers showed that in sleeping mice, the expanded glymphatic vessels cleared away amyloid-beta from the brain twice as quickly as they did when the mice were awake. This paper received a lot of attention because it shed light on a likely function of sleep: to allow the brain to clean itself. New studies quickly came forward with additional evidence, showing that amyloid-beta levels in your brain increase throughout the day and then decrease again when you sleep.

How Sleep Deprivation Can Poison Your Brain

In less than 10 years, our understanding of sleep and Alzheimer’s disease has been turned upside down. We now know that during the day, when neurons are highly active, they release amyloid-beta into the brain fluid. Then when you sleep, your brain’s glymphatic vessels expand and flush away the amyloid-beta and other waste products before they can accumulate to toxic levels. This newly-discovered relationship brings up an ominous possibility: could sleep deprivation reduce amyloid-beta clearance and thus lead to Alzheimer’s disease?

Correlational studies suggest the answer may be yes. Elderly people with insomnia and other sleep disorders are at an increased risk of dementia and have higher levels of amyloid-beta in their brains. A recent study suggested an even more troubling possibility. The paper showed that chronic sleep deprivation may cause neurons to become hyperactive, so that they excrete greater amounts of amyloid-beta into the brain. In turn, this amyloid-beta can interact with other neurons to make it harder to sleep, creating a vicious cycle that could spiral out of control and perhaps lead to Alzheimer’s disease.

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The authors suggested that sleep deprivation could start a vicious cycle, with amyloid-beta deposition increasing exponentially.

The possibility that sleep deprivation could contribute to Alzheimer’s disease is deeply concerning. The CDC reports that 1 in 3 adults routinely do not get at least 7 hours of sleep per night. The problem may be even more severe for elderly people, of whom nearly half report sleep disturbances. By not getting enough sleep, we could be accumulating toxic levels of amyloid-beta in our brains and setting ourselves up for Alzheimer’s disease as we age.

Despite being rather frightening, these recent findings also come with an aspect of hope. While seemingly a major risk factor for Alzheimer’s disease, sleep deprivation is also preventable. By prioritizing sleep as a vital facet of overall health, as well as seeking medical assistance for sleep disorders like insomnia and sleep apnea, we may all be able to reduce our risk for Alzheimer’s and perhaps even other brain diseases. So put down that phone, turn off the lights and head to bed at a reasonable hour tonight. You’ll wake up with a squeaky clean brain in the morning!

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Sleep Apnea May Contribute to Alzheimer’s Disease

*Thank you all for your patience during my one-month hiatus. To read about my adventures backpacking across Europe or my current internship researching Alzheimer’s disease in Switzerland, check out my travel blog, Brains and Backpacks.*

 

Around 3-7% of adults suffer from obstructive sleep apnea, a condition in which the upper airway tract periodically collapses during sleep. This can lead to loud snoring and poor sleep quality. If left untreated, it can contribute to a multitude of health conditions and decreased overall quality of life. Among these possible complications is Alzheimer’s disease. People with Alzheimer’s are five times more likely to have obstructive sleep apnea than the general population.

Recent evidence has provided more direct proof for the link between sleep apnea and Alzheimer’s. In an editorial published in the journal Oncotarget, researchers from Tokyo’s National Institute of Neuroscience described their recent work investigating a new mouse model of Alzheimer’s disease. To do so, they subjected the mice to intermittent hypoxia by decreasing oxygen levels in their cages for one minute, followed by two minutes of normal oxygen levels. This cycle repeated for eight hours per day while the mice slept for periods ranging from 5 to 28 days. This type of model has been used before to simulate the effects of sleep apnea.

When the researcher’s examined the mice’s hippocampi, the part of the brain responsible for long-term memory formation, they observed that many of the processes associated with aging were also triggered by the intermittent hypoxia. This suggests that sleep apnea could lead to an increased rate of aging in the brain. The mice also had high levels of hyperphosphorylated tau, a toxic protein that forms tangles in the brains of Alzheimer’s patients. These results are in line with other recent studies, which have shown that intermittent hypoxia causes neurons to become hyperexcited and produce greater amounts of amyloid-beta, another protein involved in Alzheimer’s disease.

The authors suggested that this protocol could be useful in developing new animal models of Alzheimer’s disease, since it triggers many of the disease’s pathological signatures using only an environmental stimulus. The models could be applied for studying how aging and sleep disruptions contribute to development of Alzheimer’s over time.

At present, there is not yet enough concrete evidence to conclude a direct link between sleep apnea and Alzheimer’s disease. However, if you or a loved one experiences sleep apnea or other sleep disorders, there would certainly be no harm in seeking medical help. Correcting sleep problems can lead to greater quality of life and reduced risk of many medical conditions. Perhaps Alzheimer’s is among them.

Is It Really Alzheimer’s? 10 common misdiagnoses you should know about

Doctors misdiagnose a patient with Alzheimer’s disease at alarmingly high rates, when the true cause may be a different (and often treatable) disease. In 2011, researchers conducted autopsies on the brains of 211 men who had been diagnosed with Alzheimer’s while they were alive. They found that nearly half of the brains did not possess the necessary pathology to meet an Alzheimer’s diagnosis [1]. A 2012 study reported similar misdiagnosis rates by physicians at the National Institute on Aging’s Alzheimer’s Disease Centers [2].

An incorrect Alzheimer’s diagnosis can cause a person to pay $9,500 to $14,000 annually in unnecessary medical procedures and medications [3]. Even worse, it may result in the true cause of the dementia symptoms going untreated, hastening the rate of cognitive decline. To give you the tools to reduce the risk of a misdiagnosis, I’ve compiled this list of ten common conditions that can mimic the symptoms of Alzheimer’s disease. If you or a loved one has been diagnosed with Alzheimer’s disease, be sure that you request tests to rule out these other possibilities.

1. Medication side effects

More than 100 medications can have side effects resembling symptoms of Alzheimer’s. These include a wide variety of common meds including Benadryl, Ambien, Valium, Xanax, and Lipitor [4]. It is particularly important to inform your doctor if you are on anticholinergic drugs, which include many antihistamines, antipsychotics, antidepressants, and muscle relaxants, among others [5]. These drugs block the function of a neurotransmitter called acetylcholine, which can lead to cognitive impairment [6].

2. Normal pressure hydrocephalus

The central nervous system is surrounded by cerebrospinal fluid, which cushions the brain and regulates cerebral blood flow. For unknown reasons, cerebrospinal fluid can sometimes build up in the brain cavities (ventricles) and cause them to swell, resulting in a condition called normal pressure hydrocephalus (NPH). The symptoms of NPH include progressive dementia, difficulty walking, and urinary incontinence [7]. According to the Hydrocephalus Association, NPH affects an estimated 700,000 Americans, though only 1 in 5 of these people receive the correct diagnosis [8]. As many as 10% of patients diagnosed with Alzheimer’s or other forms of dementia may actually have NPH [9]. This condition is easily detected using brain scans and can often be treated by surgically draining the excess fluid from the ventricles. Additional reading on NPH: [10], [11], [12]

3. Vascular dementia

Vascular dementia is the second most common form of dementia after Alzheimer’s. It is caused by a stroke, multiple “mini strokes,” or other cardiovascular disturbances, and can cause similar symptoms to Alzheimer’s [13]. A 2013 study found that 17% of vascular dementia patients were previously given an incorrect diagnosis for Alzheimer’s disease, which led to significantly increased medical costs [14]. Vascular dementia is very difficult to distinguish from Alzheimer’s, and the possibility of misdiagnosis should be considered if the patient has risk factors such as high blood pressure, diabetes, or smoking. There is currently no cure for vascular dementia, but steps may be taken to improve cardiovascular health and reduce the risk of further cognitive decline [15].

4. Vision or hearing loss

Cognitive evaluations such as the Mini-Mental State Examination (MMSE) may yield an incorrect diagnosis of Alzheimer’s disease if a patient is experiencing undiagnosed vision or hearing loss. Studies have shown that individuals with visual [16] or auditory [17] impairments score lower on the MMSE, despite being cognitively normal. Both of these conditions are common among the elerly population. Studies estimate that among individuals over the age of 70, 18% are visually impaired, 33% are hearing impaired, and 8% are both visually and hearing impaired [18]. Regular vision and hearing exams could not only prevent an incorrect diagnosis but also improve the overall quality of life for these patients [19], [20].

5. Depression

Depression can often mimic the early symptoms of Alzheimer’s disease. These include mood changes, withdrawal from daily activities, sleep disruptions, and difficulty concentrating [21]. Depression affects more than 1 in 20 elderly adults and the risk may be increased by the death of a spouse or chronic illness, as well as certain medical or psychological conditions [22]. The symptoms of depression can often be improved through a combination of medications and psychotherapy.

6. Thyroid problems

The thyroid gland produces hormones that regulate metabolism and other body functions. The American Thyroid Association reports that 12% of Americans will develop thyroid problems in their lifetime, and more than half of them are unaware of their condition. Both hypothyroidism and hyperthyroidism can have symptoms resembling Alzheimer’s, including forgetfulness, mood changes, and sleep disturbances. Thyroid problems are often treatable but can cause serious complications if left undiagnosed [23].

7. Vitamin B12 deficiency

Vitamin B12 plays multiple important roles in the nervous and circulatory systems. It is most commonly found in meat, fish, and dairy products. As many as 9% of Americans are deficient in this essential nutrient [24]. Risk factors include a vegetarian or vegan diet without B12 supplements, heavy alcohol consumption, and long-term use of acid-reflux medications. Vitamin B12 deficiency can lead to dementia and changes in mood or personality, which may be mistaken for Alzheimer’s [25]. Individuals with an Alzheimer’s diagnosis might consider requesting a blood test for B12 levels, or increasing their intake of B12 in the form of supplements, fortified cereals, and B12-rich foods to see if their cognitive symptoms improve.

8. Urinary tract infection

Urinary tract infections (UTI’s) are the most common bacterial infection in the United States. They primarily affect women; nearly half of all women will experience at least one UTI in their lifetime [26]. When diagnosed correctly, UTI’s are easily treated using antibiotics and rarely cause complications. However, the little-known neurological symptoms can result in a misdiagnosis as Alzheimer’s. An elderly person with a UTI is at an increased risk of experiencing delirium, which is characterized by sudden behavioral changes such as confusion, agitation, fatigue, or delusions. Be suspicious of Alzheimer’s-like symptoms if they are accompanied by symptoms of a UTI, which include frequent, painful urination and discolored or foul-smelling urine [27].

9. Sleep disorders

We all know the importance of getting 8 hours of sleep each night, but few of us are aware of just how much sleep depravation can affect our cognitive function. A 1999 study reported that 1 in 5 individuals over the age of 65 experience sleep disturbances, though only a minority seek treatment [28]. Sleep disorders such as sleep apnea, chronic insomnia, and restless leg syndrome can lead to fatigue, difficulty focusing, irritability, and memory loss [29]. These conditions can be easily detected by visiting a sleep clinic.

10. Gluten allergy

This might be the most surprising item on this list: a simple dietary change can completely reverse the symptoms of some people’s dementia. Celiac disease is an allergic reaction to gluten, a protein found in wheat, barley, and rye. Celiac was once believed to be rare, but is now classified as one of the most common autoimmune conditions. The University of Chicago’s Celiac Disease Center estimates that 1 in 133 people have celiac disease, of whom an astounding 97% remain undiagnosed [30]. Though people with celiac can live a healthy life on a gluten-free diet, undiagnosed celiac disease can have serious and even fatal consequences, including progressive dementia and other neurological conditions [31]. For individuals with celiac-induced dementia, switching to a gluten-free diet might completely reverse their symptoms [32].

 

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