Bottom Line:
Authors: Claudio Liguori, M.D., of the University of Rome Tor Vergata, Italy, and colleagues.
Background: AD is a neurodegenerative disease marked by progressive memory loss and cognitive decline and often complicated by sleep disturbance. Orexin A is part of the orexinergic system and it helps regulate the sleep-wake cycle by increasing arousal levels and maintaining wakefulness. A relationship between the orexinergic system and the AD neurodegenerative process has been examined in a few studies with conflicting results.
How the Study Was Conducted:
Results: Patients with moderate to severe AD presented with higher average orexin levels compared with controls and they had more impaired sleep compared with controls and patients with mild AD. In the overall AD group, orexin levels were associated with total tau protein levels and sleep impairment. Cognitive impairment was associated with sleep deterioration.
Discussion: "Our study has shown that, in AD, increased CSF orexin levels are linked to a parallel sleep deterioration, which appears to be related to cognitive decline. Hence, our results demonstrate that, in AD, orexinergic output and function seem to be overexpressed with disease progression and severity, possibly owing to an imbalance in the neurotransmitter networks regulating the wake-sleep cycle toward the orexinergic system promoting wakefulness."
( JAMA Neurol . Published online October 13, 2014. doi:10.1001/.jamaneurol.2014.2510. Available pre-embargo to the media at http://media.jamanetwork.com .)
Editor's Note:
Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Possible Role of Orexin in the Pathogenesis of Alzheimer
In a related commentary, Luigi Ferini-Strambi, M.D., Ph.D., of the Universitá Vita-Salute, Milan, Italy, writes: "Orexin is a neurotransmitter that plays a fundamental role in the regulation of the sleep-wake cycle by increasing arousal levels and maintaining wakefulness."
"The main finding of the study is the increase of orexin levels in patients with moderate-to-severe AD," he continues.
"Further research should clarity how to modify or improve sleep for mitigating the risk of future AD or for slowing AD progression. In particular, other studies on the role of arousal, sleep alterations and orexin in the pathogenesis of AD could suggest new preventive/therapeutic approaches," he concludes.
( JAMA Neurol . Published online October 13, 2014. doi:10.1001/.jamaneurol.2014.2819. Available pre-embargo to the media at http://media.jamanetwork.com .)
Media Advisory:
To contact author Claudio Liguori, M.D., email dott.claudioliguori@yahoo.it . To contact editorial author Luigi Ferini-Strambi, M.D., email ferinistrambi.luigi@hsr.it
JAMA Neurology