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Sleep Hormone Linked to Alzheimer’s Progression

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People with Alzheimer’s disease often have sleep problems. Now scientists may know one reason why. Italian researchers found that people with the disease produce excessive levels of a hormone called orexin that is critical for sound sleep. Sleep disruptions may, in turn, contribute to deterioration in thinking and memory, the study suggests.

Orexin, also called hypocretin, is produced in the hypothalamus, a part of the brain involved in sleep, appetite and other functions. In Alzheimer’s disease, the new study indicates, levels of the hormone in the cerebrospinal fluid, which bathes the brain and spinal cord, increase, leading to troubled sleep and contributing to declines in thinking and memory skills.

“Our study has shown that, in Alzheimer’s disease, increased cerebrospinal fluid orexin levels are linked to a parallel sleep deterioration, which appears to be related to cognitive decline,” write the authors of the study, which appeared in JAMA Neurology. They note that as the disease progresses, output of orexin becomes excessive, disrupting normal sleep and wake cycles.

Further research is needed to elucidate more fully the links between orexin, Alzheimer’s and sleep troubles. But the findings raise the possibility that drugs that block the hormone could one day be developed to treat the disease.

Earlier studies indicated that orexin levels may be disrupted by Alzheimer’s disease, though findings were ambiguous. For the current study, researchers at the University of Rome compared spinal fluid orexin levels in people with Alzheimer’s with levels in their healthy, mentally intact peers. They also assessed sleep patterns in both groups, as well as indicators of Alzheimer’s such as beta-amyloid and tau. The study included 21 participants with mild Alzheimer’s, 27 with moderate to severe Alzheimer’s, and 29 healthy controls.

The scientists found that those with moderate to severe Alzheimer’s had higher average orexin levels compared with controls. Those with more advanced disease were also more likely to have impaired sleep compared with controls and those with mild Alzheimer’s. In those with Alzheimer’s, cognitive decline was also linked to impaired sleep.

In a commentary accompanying the study, Dr. Luigi Ferini-Strambi of the Universitá Vita-Salute in Milan notes that sound sleep is necessary to clear the brain of toxic proteins. Disruptions in sleep may impair this process.

“The main finding of the study is the increase of orexin levels in patients with moderate-to-severe Alzheimer’s,” he says. “Further research should clarify how to modify or improve sleep for mitigating the risk of future Alzheimer’s disease or for slowing Alzheimer’s progression.”

By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.

Source: Claudio Liguori, MD1; Andrea Romigi, MD, PhD1; Marzia Nuccetelli, PhD, et al: Orexinergic System Dysregulation, Sleep Impairment, and Cognitive Decline in Alzheimer Disease. JAMA Neurology, Oct. 13, 2014.

Luigi Ferini-Strambi, MD: Possible Role of Orexin in the Pathogenesis of Alzheimer Disease. JAMA Neurology, Oct. 13, 2014.

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