December 23, 2009
Sleep deprivation may be bad for the brain, a new study in mice suggests.
Caregivers have long observed that people with Alzheimer's suffer from troubled sleep. But doctors were not sure whether poor sleep was a cause or effect of having dementia. This is the first study to show that long-term lack of sleep may damage brain cells and might lead to the forgetfulness of Alzheimer's disease.
In the study, researchers at Washington University School of Medicine in St. Louis found that mice that were made to stay awake had greater accumulations of the protein beta-amyloid in their brains. Beta-amyloid has long been recognized as a hallmark of Alzheimer's disease, and it is possible that its accumulation may kill off brain cells critical for thinking and memory.
The scientists also found that orexin, a protein that helps regulate the sleep cycle, appears to be directly involved in the increase. "Orexin or compounds it interacts with may become new drug targets for treatment of Alzheimer's disease," said senior author David M. Holtzman, M.D., the Andrew and Gretchen Jones Professor and chair of the Department of Neurology at the School of Medicine and neurologist-in-chief at Barnes-Jewish Hospital. "The results also suggest that we may need to prioritize treating sleep disorders not only for their many acute effects but also for potential long-term impacts on brain health."
Using advanced brain imaging techniques, the researchers found that levels of beta-amyloid increased when the mice were awake, typically during the night. Conversely, levels of the toxic protein decreased when the mice were sleeping, often during the day. Other studies have shown that people show a similar pattern, with beta-amyloid levels generally higher when someone is awake and lower when they slept.
In the current study, the researchers showed that depriving the mice of a good night's sleep led to a roughly 25 percent higher beta-amyloid levels. Levels were lower when mice were allowed to sleep. They found that three weeks of chronic sleep deprivation accelerated the accumulation of beta-amyloid plaques in the brain.
In contrast, when mice were given a chemical to block orexin and promote sound sleep, plaque deposition dropped by more than 80 percent in some areas of the brain. "This suggests the possibility that a treatment like this could be tested to see if it could delay the onset of Alzheimer's disease," Dr. Holtzman said.
Dr. Holtzman noted that not only does the risk of Alzheimer's increase with age, but the sleep/wake cycle also starts to break down, with older adults progressively getting less and less sleep. The pattern could create a vicious cycle, whereby poor sleep in midlife increases the risk of Alzheimer's. The onset of Alzheimer's could, in turn, disrupt sleep cycles, further contributing to the accumulation of brain-damaging plaques.
Investigators are considering population-based studies to see whether chronic sleep loss in young and middle-aged adults may increase the risk of Alzheimer's disease later in life. Earlier studies have not shown a link between Alzheimer's and poor sleep.
Washington University School of Medicine. Kang J-E, Lim MM, Bateman RJ, Lee JJ, Smyth LP, Cirrito JR, Fujiki N, Nishino S, Holtzman DM: "Amyloid beta dynamics are regulated by orexin and the sleep-wake cycle." Science Express, Sept. 24, 2009.