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We provide you with articles on brain science, timely topics, and healthy living for those affected by neurologic challenges or seeking better brain health.  

Sleep, Research
By Natalie Pompilio

What Researchers Are Learning About Brain Health by Studying Sleep

Research on sleep disorders and the importance of regular shut-eye has deepened our understanding of the link between sleep and brain health.

People in different apartments of a building experiencing insomnia
Illustrations by Jorge Colombo

Connor Reiff was 11 when doctors determined he had narcolepsy with cataplexy, a rare condition that manifests in extreme daytime sleepiness and the sudden loss of muscle control. After months of trial and error with different prescriptions, participation in a clinical trial, and countless conflicts with insurance providers, the Reiff family thought they had Connor's sleep issues under control.

Then, when Connor turned 13, he began sleeping for days at a time, only rising when his parents woke him to eat or use the bathroom. He'd sometimes walk in a sleep stupor, physically pushing away family members he encountered. “Our son was disappearing before our eyes,” says Connor's mother, Sarah Reiff, who lives with her family in Noblesville, IN. “This is a kid who plays soccer, who loves school, who is very involved in activities—and suddenly he isn't doing any of that.”

The eventual diagnosis was Kleine-Levin syndrome (KLS), a disorder marked by episodes of excessive sleep—up to 20 hours a day. Specialists believe the condition may be related to malfunctioning of the thalamus and hypothalamus, areas of the brain that govern appetite and sleep. More than two thirds of KLS patients are teenage boys.

Studying rare sleep disorders such as KLS has given scientists insight into why we sleep and how we can do it better. Overall, there are more than 80 sleep disorders, ranging from the mildly annoying to the potentially deadly. The best known is probably insomnia; about 10 percent of the general population has chronic insomnia, an inability to fall asleep for multiple nights over a period of months.

Addressing sleep disorders “is paramount to not only protecting the brain down the road but also on a day-to-day basis,” says Daniel Barone, MD, associate medical director of the Weill Cornell Center for Sleep Medicine in New York City and co-author of The Story of Sleep: From A to Zzz (Rowman & Littlefied, 2023). “One of the best ways to take care of our brains is by getting quality sleep.”

Intriguing Clues

Research on sleep disorders has led to improvements in treatment for a variety of sleep and neurologic conditions. Case in point: Studies in the late 1990s on the causes of narcolepsy with cataplexy—the condition Connor was initially diagnosed with—led to the development of dual orexin receptor agonists, drugs now commonly prescribed to treat insomnia. The researchers discovered that people with narcolepsy with cataplexy often had low levels of hypocretins (orexins), brain chemicals that sustain alertness and prevent REM from happening at the wrong time.

“Once they found out, ‘If I take away your hypocretin, it makes you sleepy,’ there was a new idea of how to make a sleeping pill,” says Rafael Pelayo, MD, clinical professor of psychiatry and behavioral sciences at Stanford University School of Medicine in California and a sleep specialist at the university's Sleep Medicine Center.

In another case, the research finding that REM sleep behavior disorder (RBD)—which causes people to enact their dreams—may be an initial manifestation of various disorders, including Parkinson's disease, Lewy body dementia, and multiple system atrophy, has driven further studies on RBD and neuroprotective treatments that could arrest or postpone the onset of these disorders. “Recognizing the link between RBD and future Parkinson's and dementia risk offers a window of opportunity for neuroprotection, so that once RBD is accurately diagnosed, we could treat patients in the short term to control injury risk, and in the long term to stop neurodegeneration of the brain,” says Erik K. St. Louis, MD, director of the Sleep Behavior and Neurophysiology Research Lab at Mayo Clinic in Rochester, MN.

“We don't have the treatment yet, but we remain hopeful that a safe and effective neuroprotective treatment or intervention will be identified soon, so stay tuned,” adds Dr. St. Louis, who's also associate professor of neurology at Mayo Clinic. RBD occurs in 1 to 2 percent of the general population and between 7 and 13 percent of adults age 60 and older.

Sleep disorders can disrupt not only nighttime behavior but also activities throughout the day. One of Dr. St. Louis' patients, who enjoys walleye fishing on Minnesota lakes, has type 1 narcolepsy with cataplexy—which means he can have sudden attacks of weakness, especially when experiencing strong emotions. He had several attacks triggered by the feel of a fish biting at the line and would get so excited, Dr. St. Louis says, that he often fell overboard. “We talked about safety, like always having a life preserver on. There were many times his family had to pull him out of the water. Once his condition was controlled, he safely landed several big catches,” says Dr. St. Louis.

Connor Reiff's condition, KLS, can be associated with overeating, irritability, and hallucinations, according to the National Institute of Neurological Disorders and Stroke. He twice tumbled out of his second-floor bedroom window while asleep, and though he was not seriously injured either time, he now has a full-time aide and keeps an alarm on his bed that goes off if he gets up.

Now 19, Connor experiences fewer periods of extreme sleep, thanks to six daily prescription medications, including sodium oxybate (Xyrem) and pitolisant (Wakix), both of which prevent the sudden onset of daytime sleepiness and muscle paralysis. For those with KLS, episodes generally decrease in frequency and intensity over the course of eight to 12 years. “His trajectory is going to be different from that of other kids, but it's still a path to success,” Connor's mother says. “He's going to do well in this world. It's just going to take a little longer.”

Some disorders that aren't necessarily dangerous can indicate a more serious underlying problem. For example, sleep talking (somniloquy) is considered a normal variant of sleep, but doctors take note when patients 50 years and older begin doing it because it could be an early sign of RBD. Sleepwalking, or somnambulism, is usually benign, but it too can signal the onset of RBD, especially if the sleeper seems to be acting out a dream.

Protective Factor

Inadequate sleep has both short- and long-term effects. People who sleep less than seven to eight hours each night may experience daytime sleepiness, forgetfulness, or an inability to concentrate the next day. Over the long haul, lack of sleep may lead to an accumulation of waste products in the brain. Research published in Science in November 2019 found that cerebrospinal fluid appears to synchronize with brain waves during sleep, clearing the brain of metabolic waste products in rhythmic, pulsing patterns. The project involved 13 participants ages 23 to 33, prompting researchers to wonder what a study involving older participants would reveal. Older adults can have sleep problems because of age-related conditions or medications. They also have reduced non-REM slow wave activity, which could lead to more accumulation of neurotoxic products in the brain, Dr. St. Louis says.

The study authors note that it's unclear if there's a link between the cerebrospinal fluid's work and the slow waves in neural activity that contribute to memory consolidation. “Sleep specialists are certain that during sleep, especially deep sleep, the brain clears out the byproducts of daily living,” says Dr. Barone. “The converse of that is that if we don't sleep well over many years and decades, the brain may not be able to clear out these bad products. The belief is that the buildup of waste products over this long time span can contribute to Alzheimer's disease and other degenerative illnesses.”

A 2021 study in Neurology found an association between robust function of the glymphatic system—which clears waste from the central nervous system—and better language scores, word recall, and higher gray matter volume in older adults.

Poor sleep also may contribute to mood problems. An article in the May 2021 edition of Frontiers in Psychiatry noted there was mounting evidence of “a close relationship between sleep disturbance and mood disorders, including major depressive disorder and bipolar disorder.”

We spend about a third of our lives sleeping, but even after decades of research, questions persist about what happens while we slumber. “We commonly say that sleep is restorative. You surely feel refreshed after a good night's sleep, but what is actually being restored?” asks Dr. Pelayo. “[Learning more about] the function of sleep is ultimately going to tell us how our brains really work.”

Additional important physiological functions that occur during sleep include building memories, processing information and emotions, restoring metabolic balance, and rebooting the immune system, according to Dr. St. Louis. In 2009, researchers discovered that a lot of bone growth occurs in children while they sleep, in part because lying down removes pressure and allows their bones to elongate. Another study, published in 2011 in the Journal of Clinical Densitometry, found that shorter sleep could impair bone mass.

Valuable Asset

Some people treat not getting enough sleep as a point of pride—a sign of hard work or an active social life—despite the potential health risks. “There used to be an attitude of ‘I'll sleep when I'm dead,’ and there's an increasing recognition that a lack of sleep may actually hasten that result,” says Brendan P. Lucey, MD, associate professor of neurology and head of sleep medicine at Washington University School of Medicine in St. Louis.

Too little sleep has been associated with multiple negative health outcomes, including obesity, high blood pressure, diabetes, and metabolic dysfunction. And untreated sleep apnea can contribute to cognitive problems, says Dr. Lucey.

Dr. Barone admits to pulling all-nighters in college and medical school, “but the more we learn, the more we realize that we shouldn't be doing that.” There's also something to the expression “sleep on it,” says Dr. Pelayo, who remembers reading his medical textbooks until the words on the page became blurry, falling asleep, and then waking up feeling he had a better grasp of the material he'd last read.

Positive trends in the study of sleep include the ever improving therapeutics that can treat a broad range of sleep disorders, Dr. St. Louis says. Another is that sleep is now recognized as a “multi-disciplinary team sport,” with primary care physicians, pulmonologists, psychiatrists, ENT specialists, and others joining neurologists in its study.

“There's still an endemic problem of sleep deprivation in our society. That's hard to make go away,” Dr. St. Louis says. “But over the last decade we're paying more attention to sleep, which is a good thing, and there's more messaging that sleep is one of the three pillars of health. Diet, exercise, and sleep are the three things we can all control to try to optimize our performance, longevity, and quality of life.”

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