November 10, 2015
Sleep could be the missing link in dementia
By Mark Taylor, Chicago Tribune
Mom was right. Getting a good night’s sleep may prove even more important to long-term health than our parents advised.
Scientists already have documented connections between sleep loss and memory problems, which explains why many schools are starting classes later. But a growing body of research is exploring links among sleep deprivation, sleep disturbance and Alzheimer’s disease, the most common form of dementia.
The number of Alzheimer’s patients is expected to double by 2020, due primarily to the increased longevity of the baby boomer generation. More than 50 million Americans suffer from sleep disorders, which can be debilitating, according to the U.S. Centers for Disease Control and Prevention.
Poor sleep is a common symptom of Alzheimer’s patients, particularly those suffering moderate to severe forms of the cognitive disorder. Physicians treating Alzheimer’s patients say they often awaken in the middle of the night and wander or remain awake at night and sleep during the day. Researchers still haven’t established whether the poor sleep causes Alzheimer’s or is only a symptom of the incurable disease.
But Dr. Erik Musiek, an assistant professor of neurology who practices at Washington University in St. Louis, said there has been a paradigm shift in understanding the relationship between sleep and the incurable disease, which affects 5.3 million Americans.
He said scientists have known for years that people with Alzheimer’s have problems with sleep and disruptions in their circadian rhythms, which are governed by the internal biological clock that regulates the timing of periods of sleep and wakefulness. But he said new research suggests that sleep and circadian rhythm problems experienced earlier in life actually may contribute to the risk of Alzheimer’s and accelerate the disease.
Musiek said researchers have observed that sleep-deprived mice have greater amounts of beta-amyloid plaque forming in their brains. Beta-amyloid and tau are proteins that accumulate in the brains of Alzheimer’s patients and are toxic to nerve cells. “We don’t yet know what kinds of sleep problems predispose you to Alzheimer’s. We do know that people who sleep too little or too much are at risk,” Musiek said.
Washington University’s center researchers are trying to understand how circadian rhythms control beta-amyloid levels in the brain, he said.”If we can give drugs that improve sleep and lower levels of beta-amyloid, maybe those patients won’t get those harmful plaques or get Alzheimer’s later in life. We’re looking at sleep as a potentially modifiable risk factor.”
Adam Spira, an associate professor in the Department of Mental Health at the Bloomberg School of Public Health at Johns Hopkins University, said research exploring the connection between sleep and Alzheimer’s has grown since 2009, when the key mouse study that Musiek described was published.
But in recent years, studies using wrist actigraphy — medical grade monitoring devices that monitor wrist movement during sleep — and polysomnography, the gold standard of sleep research that measures heart rate, blood oxygen and other measurements, have begun to examine links between disturbed sleep and Alzheimer’s in humans. “Using these devices and other tools, including PET scans that measure the amount of amyloid in living human brains, researchers are finding those connections between sleep disturbance and the risk of cognitive impairment and decline, as well as Alzheimer’s and other dementias.”
He said that 2009 Washington University study findings were very exciting “because we saw the beginning of a causal link between sleep disturbance and Alzheimer’s.” He said his Johns Hopkins colleague, Dr. Mark Wu, recently showed similar links between sleep deprivation and amyloid deposits in a fruit fly model of Alzheimer’s, providing further evidence that sleep loss may contribute to Alzheimer’s.
Spira said the central goal of researchers right now is identifying ways to prevent Alzheimer’s. He noted that science has developed good treatments for sleep disturbances, and researchers are wondering whether treating disturbed sleep could prevent or delay Alzheimer’s. A 2013 Washington University study showed that people with less efficient sleep — those who spend smaller proportions of time in bed sleeping — tended to have more beta-amyloid in their brain, as measured in their cerebral spinal fluid.
“This was the first objective measure of sleep linking the amount of amyloid in the brain in people who are cognitively normal.” Spira and his colleagues at Johns Hopkins and the National Institute on Aging conducted a study of 70 seniors in the Baltimore Longitudinal Study of Aging who reported their sleep habits. Using PET scans, they found that those reporting poorer sleep quality and shorter sleep duration had higher amounts of beta-amyloid in their brains than those who reported sleeping longer and better, he said. An ongoing longitudinal study hopes to explore whether disturbed sleep is associated with subsequent amyloid deposition, brain atrophy and cognitive decline.
“We don’t know whether there is a causal link. More research is needed,” he said, adding, “but sleep is gaining attention as a potential contributor to Alzheimer’s.” New research led by Dr. Maiken Nedergaard at the University of Rochester in New York state may lead to a different approach to treating Alzheimer’s. Nedergaard said sleep alters the cellular structure of the brain. Her lab discovered that the spinal fluid of mice swirled around their brains as they slept, functioning like a dishwasher.
“We found that in those mice beta-amyloid is efficiently cleaned out during the sleep process. This cleaning of the brain is a distinct function not compatible with wakefulness. Our hypothesis is that during sleep, our brains function as dishwashers to clean and clear out beta-amyloids. We observed that when we kept them awake, the spinal fluid did not flow back into the brain.”
Nedergaard said her lab’s findings may open new avenues for targeting and treating Alzheimer’s. She envisions a kind of “immunotherapy.” “I could imagine finding a way to enhance this dishwasher function that would wash away what (plaque) is already stuck there,” she explained, “but we’re a long ways away from that. For 10 years, science has been interested in finding ways to block beta-amyloid production but with little success. This suggests a new approach.”
Dr. Sigrid Veasey, a professor of medicine at the University of Pennsylvania‘s Center for Sleep and Circadian Neurobiology in Philadelphia, said there is strong evidence to support the theory that Alzheimer’s can be worsened by sleep deprivation. Veasey said her lab has confirmed that chronic sleep loss causes direct injury to parts of the brain that play essential roles in attention span and memory consolidation. Veasey’s lab is studying whether those injuries could shift the course of Alzheimer’s.
“We don’t yet believe that sleep loss causes Alzheimer’s,” she said. “But if you were predisposed to get it at 85, it’s possible that sleep disturbance might make it likelier that you would get it much earlier, at age 65 or 75.” Veasey said her lab used mice as stand-ins for people constantly scheduled to perform shift work. Over a four-week period, she noted, the sleep-deprived mice lost neurons. And she said those injuries can accelerate beta-amyloid production and cause increased inflammation in the brain.
And she said examining self-reported data from patients enrolled in long-term studies has shown that years of chronic sleep loss have had an impact on cognition. Veasey predicted that researchers are three to four years away from developing molecular models for humans. “I think we’ll move relatively fast with the luxury of animal models, fruit flies and mice and get to the bottom of this mechanism quickly.”
Healthier sleep means healthier brains
To enhance the health of sleep, get regular aerobic exercise, eat a healthy diet, avoid alcohol, and don’t eat or drink too soon before going to bed.
- Exposure to light, even from television and cellphones, can impact circadian rhythms and confuse the brain and your body clock, so eliminate as much light as possible in your bedroom.
- Take sleep seriously.
- Organize your next day before going to bed. Look at the humidity and temperature of the room, and adjust accordingly.
- Cooler is generally better than warmer.
- If you wake up frequently at night, try to write down your habits and think about what you’re doing, whether it’s napping during the daytime, awakening too early or some other cause. Examine your sleep positions.
- If you have trouble sleeping attributable to sleep apnea or poor breathing, see a physician.
- Don’t stay up too late. Aim for a consistent bedtime in a dark room. Bright light in the morning resets your circadian clock, so upon waking, open the windows and turn on the lights.
- A calorie-rich breakfast helps synchronize your body clock.
One couple’s struggle
Barb Ziemba said that when her husband doesn’t sleep, she doesn’t sleep. Ziemba, 69, of Chicago’s Bridgeport neighborhood, is caretaker for her husband of 50 years, John Ziemba, 75, a former design engineer diagnosed with Alzheimer’s disease four years ago.
“He sometimes awakens in the middle of the night, turns on the lights in the kitchen and bathroom, and tries to start his day,” she said. “I wake up, take him by the hand and lead him back to bed. It disrupts my sleep more than his. I try to catch a nap during the day, but often I can’t and just have to keep going.”
Sometimes, the mother of four said, caring for her husband “is like having a 180-pound baby.” Ziemba, who lost her job with a health care real estate investment trust in 2008 and now cleans homes for extra cash, said she can’t afford to go without sleep. Her husband is one of an estimated 5.3 million Americans afflicted with Alzheimer’s, the most common form of dementia. Most of them — 5.1 million, or 96 percent — are age 65 or older, according to the U.S. Census Bureau.
Physicians treating Alzheimer’s said that in the moderate or severe stages, patients often sleep poorly, awakening in the middle of the night and wandering, or remaining awake at night and sleeping during the day. “If I’m taking a nap and no one else is home, there is an issue of safety, because I don’t know if he’ll roam the streets,” Ziemba said. “So I always have to be on alert, and that’s very stressful.”
Sleep deprivation and disturbed sleep have long been associated with Alzheimer’s and are among the leading reasons for the families of Alzheimer’s patients to seek nursing-home care, said Theresa Dewey, a licensed clinical counselor and care navigator with the Alzheimer’s Association, Greater Illinois Chapter at Alexian Brothers Neurosciences Institute’s Memory Disorders Center in Elk Grove Village. Dewey said failure to sleep is one of the top complaints from caregivers.
“They wonder how they can function and continue to care for mom or dad if they’re not sleeping and keeping everyone else awake,” Dewey said. “Their days and nights become flip-flopped.” Dr. Concetta Forchetti, a neurologist with Alexian Brothers Neurosciences Institute, said many Alzheimer’s patients have sleep apnea, a breathing disorder that causes sleep disruptions. She said studies have shown people with sleep apnea who average less than six hours per night have a higher risk of developing cognitive impairment.
“When they do awaken at night, it is dark, and there are noises, so some become agitated and frightened. It’s a serious problem often making it unsafe for them to be at home. The reversal of the day-night cycle is common.” Forchetti, who has treated Alzheimer’s patients for more than 26 years, said falling asleep usually isn’t the problem; it’s having interrupted sleep.
Forchetti said researchers understand that sleep has a restoring function. “Biologically we don’t still have a comprehensive explanation for why we sleep. This is still an understudied territory.” But answers can’t come fast enough for Barb Ziemba.
“It’s disheartening,” she said. “It’s scary how many people have Alzheimer’s. And its impact on families can be devastating.”
Sources: Alzheimer’s researchers Maiken Nedergaard, Sigrid Veasey and Erik Musiek.