The quest for rest: Sleep could be the key to fighting Alzheimer’s—and a huge business opportunity

It’s understandable why Lim would be a bit of an alarmist, so to speak, when threatened with a lack of a consistent night’s sleep. A neurologist at the Oregon Health & Science University and a sleep disorders physician at the VA Portland Health Care System, Lim is at the forefront of a global cadre of medical researchers who have in recent years been pinning down the ways in which even moderate sleep deficiencies in middle age strongly link to Alzheimer’s disease and dementia later in life. “We used to think that sleep problems were just another symptom of Alzheimer’s,” she says. “Our big discovery was that the lack of sleep involves brain processes that may develop into the disease.”

The finding that getting more and better sleep could offer the best, and possibly only, way to significantly reduce the risks of neurodegeneration in older age—along with new insights into a range of other health benefits—is likely to further fuel an already hot sleep industry. Market research firm Infinium Global Research puts the current worldwide market for sleep aids—including drugs, devices, special bedding, and health care services—at an estimated $80 billion–plus, and predicts it will climb to $114 billion over the next five years. Research firm BCC has been projecting a similar growth rate. But these estimates were calculated before the new links to long-term neurodegeneration hit the journals. Now Tim O’Brien, who heads life sciences content at BCC, says he’s watching for “a sudden leap.” 

That leap would be driven not only by consumers’ intensifying pursuit of better sleep-related health, but also by a stream of new therapies and technologies that are emerging to help achieve it, from sleep drugs to implantable medical devices to smart pillows. “Concerns about getting a good night’s sleep are now on the same level as concerns about other major health disorders,” says Ashton Udall, who heads up Google’s Nest smart-device line, some of which is getting a range of sleep-related features. “People are looking for help.”

Brain drain

It’s not exactly news that sleeping poorly makes us feel lousy and less sharp. Studies have shown that a shortage of sleep causes 13% of injuries to workers and costs companies $3,500 per affected employee in absenteeism and reduced productivity. Car accidents climb by 10% on the day after a time-zone change. The chronically sleep-deprived are not a rare breed: Estimates of the percentage of adult Americans who regularly have trouble falling or staying asleep range from 50% to 75%, leading the CDC to label sleep deficiency a public-health epidemic. A Rand Corporation report reckons the widespread inability to regularly get at least six hours of sleep costs the U.S. economy $225 billion a year, and other studies have put the costs as high as $410 billion. (Those headlines about the health risks of sleeping too much? Ignore them, say sleep experts. The regular need for more than about eight hours of sleep is usually caused by an underlying health problem, not vice versa.)

Researchers are uncovering a bevy of new insights into just how far-reaching the impact of not sleeping enough hours—or not sleeping deeply enough—can be. Studies have shown that sleep deficiency can wreak havoc with the body’s metabolism, leading to fatigue, weight gain, and other problems. “When you get enough sleep you’ll not only feel better, be in a better mood, and be more resilient to injury and disease, there’s even increasing evidence other people will find you more attractive,” says Charles Czeisler, a researcher and physician at Boston’s Brigham and Women’s Hospital and director of the Harvard Medical School’s Sleep Medicine Division. Czeisler adds that the mounting evidence even has the military rethinking its reliance on sleep deprivation as a means of toughening troops up in training. The number of scientific journal articles about sleep and sleep disorders published annually has roughly doubled in the past five years, hitting 3,000 articles in 2020, according to industry research firm PatSnap.

But it’s the discovery of the apparent long-term impact of sleep on the aging brain that has sleep researchers buzzing—and that promises to send consumers scrambling for sleep-boosting solutions. It has been known for decades that people with Alzheimer’s tend to sleep poorly, but scientists saw sleep trouble as a symptom, not a possible cause or accelerant, of the disease. Then in 2009 Lim and colleagues showed that mice genetically engineered to suffer an Alzheimer’s-like disease formed the disorder’s signature brain plaque much more quickly when they were deprived of sleep. “We showed the process of removing plaque is very active during sleep, and not active during the day,” says Lim.

But did the findings apply to humans? That critical question remained open until this year, when two large epidemiological studies came out to show that lack of sleep in middle age was a strong predictor of Alzheimer’s and other forms of dementia decades later. One of the studies tracked some 8,000 people in Britain for 25 years starting at age 50, finding that those who slept six hours or less a night had a 30% greater risk of developing dementia later. “Now we think it’s important to establish good sleep habits in earlier adulthood to help reduce the risk,” says Séverine Sabia, who researches sleep at Inserm in Paris and University College London, and was lead author of that study, published in April in Nature. “We may even be able to use sleep interventions to delay the progress of the disease for someone already on the path to Alzheimer’s.”

The other study, published in February in the journal Aging, followed just under 3,000 people age 65 and older for five years, finding that those who didn’t get at least five hours of sleep per night on average had twice the risk of dementia. “We used to think there was little we knew to do to reduce the risk, but now the science suggests that improving sleep might work,” says Rebecca Robbins, a sleep scientist at Brigham and Women’s Hospital and a Harvard Medical School instructor, and lead author of the study. Czeisler, also an author of the study, notes that the poor-sleeper participants were up to four times as likely to die during the study, and had triple the rate of hardening arteries. Lim, meanwhile, is now trying to gather evidence that the accelerated plaque accumulation she found in sleepless mice similarly occurs in humans, which would represent a smoking gun.

It’s hard to overemphasize the potential impact of the discovery of an effective approach to curtailing Alzheimer’s. One out of eight people who live beyond age 55 eventually develops Alzheimer’s or another form of dementia, leading to $655 billion a year in medical and other costs in the U.S. alone. There’s only one drug approved—recently and controversially—by the Food and Drug Administration to treat Alzheimer’s, and it’s widely expected by experts to be of only small benefit to only a small minority of patients, at enormous cost. As the public catches on to the fact that better sleep in middle age may well provide a heavy dose of protection, the quest for rest could reach a frenzy.

Pills, pumps, and pulses

The sleep industry is ready to oblige. For many of the restless, the first reaction will be to join the nearly 10 million Americans who take prescription pills to try to get more or sounder sleep, spending more than $4 billion a year on them. A quarter of that market is for benzodiazepines like Valium, which are tranquilizers that can also ease anxiety. Most of the rest is for what the industry calls “Z-drugs”—zolpidem (Ambien), zopiclone, zaleplon, and eszopiclone (Lunesta)—which amplify the sleep-promoting neurotransmitter GABA, often inducing sleep with fewer side effects than other drugs.

But research hasn’t been encouraging about the long-term benefits of any currently available sleeping pills. A study published in May in BMJ Open found that after two years those who regularly took pills didn’t report getting more sleep than a similar group that went pill-less. More troubling was a study conducted by Robbins and colleagues that seemed to show taking pills was linked to an increased risk of later dementia. That association may have more to do with the sleep challenges that drive subjects to take pills in the first place rather than the pills themselves, notes Robbins, but it does suggest that the pills commonly taken today aren’t the right approach to lowering dementia risk. “They may help get you down, so to speak, but you won’t get the wonderful benefits of natural sleep,” she says.

Well aware that a pill providing a more natural sleep experience would likely be an explosive blockbuster, researchers and pharmaceutical companies are busy trying to come up with drugs that come closer to that goal. Tokyo-based pharma Eisai last year introduced Dayvigo, a drug that works by blocking the action of certain neurotransmitters that promote wakefulness. “We’ve got the latest mechanism of action,” says Margaret Moline, a neuroscientist who heads Eisai’s neurology business. “And we’re looking at other neurotransmitters that might be good targets.” But so far there’s little evidence the results are closer to natural sleep. 

Particularly intriguing is research into ways of targeting the circuits in the brain that appear to specifically control the deeper sleep stages that seem linked to the greatest brain-health benefits. Work pioneered by University of Massachusetts Medical School sleep scientist Christelle Anaclet and colleagues has shown that stimulating a region of the mouse brain called the parafacial zone can keep mice in what their brain waves indicate is natural deep sleep for as long as six hours—some 20 times as long as they normally sleep at one shot. “We think there’s a good chance we can make progress in finding a drug that stimulates a similar brain region in people,” says Anaclet. She adds that her lab is also looking at whether the deeper-sleeping mice are more resistant to Alzheimer’s-like disease.

In the meantime, many Americans are turning to cannabis products to boost sleep, in spite of the fact that studies haven’t found much long-term benefit to them along those lines. According to cannabis market research firm Brightfield Group, 72% of cannabis users report getting high “right before bed,” and among the nearly 50 million Americans who have tried CBD, better sleep was the No. 1 reason. “We’ve really seen sleep interest take off in the past two years,” says Chris Van Dusen, chief growth officer at Balanced Health Botanicals, whose Denver-based CBDistillery subsidiary is a well-established brand. The company offers a gummy containing a mix of CBD and melatonin—a popular over-the-counter sleep aid—and it’s a bestseller, Van Dusen says. He adds that a new up-and-comer for the company is a gummy that combines CBD with CBN, another nonpsychoactive cannabis compound claimed by many, albeit without much evidence, to promote sleep.

Another huge sleep-aid market is the one tied to sleep apnea, a disorder in which narrowing airways or faulty nerve signals during sleep can leave sufferers gasping for air, making sound sleep all but impossible. About 7 million people in the U.S. are diagnosed with apnea, but the American Academy of Sleep Medicine estimates another 23 million have it but either don’t know it or ignore it. The true number is likely even higher, says Czeisler, noting that those with undertreated apnea are among the hardest hit by long-term health problems related to sleep deficiency. Studies by Czeisler and colleagues have found apnea sufferers show signs of cognitive impairment 10 years earlier than others on average, and of Alzheimer’s five years earlier, while being six times as likely to die prematurely. “Researchers have finally started ringing the alarm bells about this,” he says.

The main treatment for apnea is a so-called CPAP machine or similar device capable of pushing air into the lungs of an afflicted sleeper by pumping it through a fitted, semirigid face mask. These machines start at about $500, but many now run to $3,000 and more as manufacturers add in everything from custom mask-fitting to auto-adjusting two-way airflow to wireless connectivity for data collection. All told it’s already a nearly $4 billion market globally, estimates BCC, with some 5 million CPAP users in the U.S.

But about 40% of patients told by a doctor to use a CPAP machine either refuse, or stop using it, usually because of anticipated or actual discomfort and bother. A small percentage of CPAP refuseniks elect instead to have tissue surgically removed from the back of their mouths and top of their throats, a procedure that carries a risk of complications and painful recovery, yet has only about a 25% success rate in mitigating the problem. A newer alternative is “neuromodulation,” which involves minor outpatient surgery to implant a tiny device and wire that senses breathing at night and sends an electrical pulse to the tongue to get it to flex and open up the airway. Inspire Medical Systems, headquartered just outside Minneapolis, offers the only FDA-approved device, with studies showing a 79% reduction in sleep apnea problems for the more than 10,000 patients who have received it. Now London-based LivaNova has a version in clinical trials. John Webb, who heads up the company’s apnea-related business, thinks the stream of bad news about sleep problems will drive interest in the technology. “We’re anticipating a definite spike in awareness,” he says.

Hit the sack—and track

For those poor sleepers who don’t have apnea and who prefer to avoid the drug route, a growing array of products beckons. Consider the $200 Zerema smart pillow, which the company claims enlists artificial intelligence to detect snoring and learn sleep patterns in order to automatically raise or lower the height of the pillow so as to adjust airways and optimize sleep. The $70 Zeeq pillow doesn’t change shape, but it does listen for snoring and vibrate in response, presumably as a means of interrupting the noisy breathing. It also streams music and controls smart-home appliances like lights. The Luuna “intelligent sleep mask”, currently available for preorder at $199 on Kickstarter, promises to monitor electrical activity in the sleeper’s brain and play music that is “pretty much composed by your brain waves.” And any number of “light-therapy” boxes or glasses offer to straighten out your circadian rhythm—the body’s internal timing signal that tends to sync sleepiness with nighttime—by briefly exposing the eyes to bright blue or green light in the morning. Adventurous shoppers, meanwhile, can explore a trove of more exotic sleep gadgets via Gearbest, the giant Chinese online retailer that sells and ships to the U.S. Among the finds there are devices that promise to improve sleep by beaming electricity and laser light up your nostrils, or magnetically dilating them.

As with pills, none of these products get ringing endorsements from leading sleep experts. “There’s no clear evidence so far on their usefulness,” notes Inserm’s Sabia. On the other hand, nasal lasers and magnets aside, no one seems ready to rule them out, either. In fact, studies have found sleep and brain-health benefits to getting troubled sleepers off their backs and onto their sides, to piping in sounds that are in sync with deep-sleep brain waves, and to exposing people to various types of light at certain times of day—an approach that Lim of Oregon Health & Science University is studying with sleep-deficient patients. But the verdict is still out on most of these gizmos.

On the other hand, experts are virtually unanimous in recommending one particular approach for tackling non–apnea-related sleep problems: Regularly get to bed earlier, and in a more relaxing environment. “There’s no substitute for giving yourself the time you need to sleep,” says Czeisler. Throw in a quiet, dark room and some soothing thoughts and low-key activities in the hour or so leading up to bedtime, he adds, and most people will find their insomnia improves. 

The American Academy of Sleep Medicine advises those who need help beyond this basic “sleep-hygiene” approach to consult a therapist, sleep coach, or other practitioner who can provide a four- to eight-session course of “cognitive behavioral therapy for insomnia,” or CBT-I, which offers other exercises and strategies to further ease the path to deep sleep. The sleep-related services industry itself is a thriving one, with the AASM counting some 11,000 accredited sleep centers and health care professionals among its members—and that would represent only a fraction of the professionals and practices that offer sleep-related services at least as a sideline. A full sleep study at a clinic, where technicians monitor a wired-up patient’s sleep, or lack thereof, can easily run to several thousands of dollars, but may be necessary for a formal diagnosis of sleep apnea.

There is, in fact, one type of gadget that most experts are endorsing—not instead of behavioral approaches like sleep hygiene and CBT-I, but as a way of getting more out of them. That’s sleep trackers, or electronic devices and apps that can monitor how long and deeply users are sleeping, and in some cases point out ways to make improvements. Robbins notes that a 2018 study found that a third of adults were already tracking their sleep with some sort of device, and estimates it’s closer to half now. “Anyone curious about how well they’re sleeping should try one as a first step, before going to get a sleep study,” she says.

The most popular sleep trackers are wearables, usually as watches or wristbands. Market research firm IndustryARC puts the current wearable sleep tracker worldwide market at $3 billion, and PatSnap estimates a 16% annual growth rate for the sleep technology market over the next four years. Wearable trackers typically measure heart rate through optical sensors, and body movement with accelerometers, using the information to infer not only length of sleep time but also how much of the time was spent in deeper stages of sleep. The technique is about 70% accurate in identifying sleep stages, says Conor Heneghan, a scientist who heads sleep research for Fitbit, the wearable manufacturer bought by Google in January. Heneghan notes that compares to about 95% accuracy from a gold-standard sleep-lab EEG reading, which measures electrical activity in the brain through an electrode-studded skullcap.

Fitbit’s companion app offers a range of insights and exercises aimed at boosting sleep—many available with an only $9.99 per month premium subscription—including sleep “scores” that break down different aspects of sleep, recommendations for when to get to bed and when to wake up, deep breathing and mindfulness exercises, and more. “There’s good evidence that these supports do have a positive impact on sleep,” says Heneghan, adding that an earlier Fitbit study suggested the efforts averaged an additional 15 minutes of sleep per night. He says the company is planning on adding in snoring detection, and may down the road be able to identify sleep apnea problems, perhaps even with FDA approval. 

Apple, too, provides sleep-support features in its Apple Watch apps, including the ability to set up a custom “wind down” bedtime routine. And wearable maker Whoop offers a $30 per month service that can recommend when you need more or less sleep based on your workouts, screen time, and alcohol and caffeine consumption. The U.S. Navy tested Whoop on its bomb-defusing specialists—talk about stressful jobs—and determined the support added an average of 45 minutes of sleep per night.

Aside from its Fitbit unit, Google is making a big push into the market by packing a number of sleep-tracking and -promoting features into the latest version of its “Nest Hub” smart speaker-and-screen device. Google’s Udall says the idea for doing so came when the company was surprised to discover that about one out of five Hubs was ending up in the bedroom. Meanwhile, its user surveys indicated the main reason people neglected to stay with sleep-tracking was finding wearables uncomfortable at night, or simply forgetting to put them on. To avoid that friction, the new Hub uses microphone and radar to contactlessly track from bedside what’s happening with the nearest sleeper, including the rising and falling of the chest. “Is there snoring? Are legs kicking? What’s happening in the surrounding environment?” he says. “We have the details waiting for you in the morning, without you having to think about it.” The information is presented in an eight-point report about sleep duration and quality, he adds.

These sorts of gadgets are catching on with consumers, says Julie Ask, principal analyst with Forrester Research, who studies the wearables market. But don’t expect too much from the devices, she adds. “The tech can help with nudges, but people still have to develop the healthy habits,” she says. “It’s best at accelerating good outcomes for those who are already committed to doing that.”

In fact, the gadgets can sometimes cause more problems than they solve, says Eisai’s Moline. “When an app is telling you you’re not sleeping well, it can cause distress,” she says, noting that there’s a medical term for excessive stress about getting enough sleep—orthosomnia—and that smart devices are spurring more cases. On the other hand, a little stress about rest may be just what the sleep doctor ordered, if it leads to a solution that smooths the snooze.