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Study: Chronic Sleep Deprivation Worsens Alzheimer's Disease

People who do not get enough sleep could be at increased risk for Alzheimer's disease, according to a new study. Researchers say their findings suggest the human sleep-wake cycle could play a major role in development of the degenerative neurological disorder, which leads to dementia and eventually death.

One of the hallmarks of Alzheimer's disease is the formation in the brain of amyloid plaques - essentially clumps of protein material that eventually overwhelm the brain's ability to function. The plaques are formed by toxic accumulations of the protein amyloid beta peptide. This is a protein fragment of the plaques which may serve a useful function in the brains of healthy individuals.

Researchers at Washington University in St. Louis, Missouri found new evidence that levels of this peptide are influenced by how much sleep people get.

They measured levels of beta amyloid protein and found concentrations of the plaque-forming peptide are higher when people and mice predisposed to Alzheimer's spend more time awake than asleep.

David Holtzman, head of the University's Department of Neurology, theorizes that it may have to do with increased brain activity. "If that's true, that might be why it generally is higher during wakeful periods and lower during sleep; because it's released with activity which occurs during wakefulness," he said.

Investigators found that sleep-deprived mice showed a 25 percent increase in amyloid beta protein levels.

The finding suggests that people who are chronically sleep deprived, such as those with a condition known as sleep apnea, are at higher risk for developing Alzheimer's because their brains are not getting enough rest. Patients with sleep apnea experience breathing difficulties that can rouse them out of their sleep hundreds of times per night.

Washington University researchers discovered that in laboratory mice specially-bred to develop the disease, they could either accelerate or arrest progression of Alzheimer's with another brain chemical, called orexin, that's also involved in the sleep-wake cycle.

Scientists say people with a condition called narcolepsy, which causes severe daytime sleepiness, have low levels of orexin.

Holtzman says when researchers injected high levels of orexin into the brains of laboratory mice, the animals stayed awake longer, causing them to develop much more serious cases of Alzheimer's, at a faster rate and at an earlier age, than they might normally.

But scientists were able to stop the progression when they injected a drug called almorexant that blocked production of orexin. "It's a very interesting study. Not too unexpected," he said.

Steven Park, an ear, nose and throat specialist at New York Medical College, says other studies have shown that Alzheimer's patients benefit from a standard treatment for sleep apnea called positive airway pressure, or CPAP that keeps the airways open during sleep.

Park says up to 90 percent of Alzheimer's patients may suffer from sleep apnea. If true, beta amyloid levels may be lower in patients who sleep better and longer as a result of CPAP. "Patients who have both sleep apnea and Alzheimer's, because there's this connection between the two, when you treat these Alzheimer's patients with CPAP, their rate of cognitive decline diminish. So it definitely does affect their rate of mental functioning," he said.

Washington University's David Holtzman says his laboratory's findings have implications for the development of drugs and other strategies to slow the onset of Alzheimer's disease, which can often begin developing in mid-life. "..not wait [ing] until somebody already has the disease going on. And also that getting appropriate sleep and trying to treat disorders of sleep might have implications down the road of perhaps affecting this process later in life as well," he said.

The study by researchers on the sleep-wake cycle and Alzheimer's disease is published this week in Science.