Lose sleep, lose your mind?
Sleep woes earlier in life may link to Alzheimer’s.
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 babyboom 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 betaamyloid 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.
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 selfreported 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.”