RESEARCH HIGHLIGHTS Nature Reviews Neurology advance online publication 28 October 2014; doi:10.1038/nrneurol.2014.209
ALZHEIMER DISEASE
Increased orexin level correlates with sleep disruption and cognitive decline in Alzheimer disease
Yen Teoh/Hemera/Thinkstock
Overactivation of the orexinergic system progresses in parallel with sleep impairment and cognitive decline in Alzheimer disease (AD), according to new research by Claudio Liguori and colleagues from the University of Rome Tor Vergata, Italy. Orexin increases arousal and maintains wakefulness, and dysregulation of orexinergic system might contribute to the
increased wakefulness after sleep onset that is observed in AD. This sleep disruption could result from imbalance between the cholinergic and orexinergic systems owing to cholinergic depletion, which is characteristic of advanced AD. Liguori and colleagues collected cerebrospinal fluid (CSF) samples from 48 patients with AD and 29 control participants, and analysed CSF levels of orexin and AD biomarkers, including amyloid-β1–42 and tau. The participants also underwent polysomnography and Mini Mental State Examination (MMSE). On the basis of MMSE scores, the patients were divided into groups with mild AD or moderate to severe AD. “We found intriguing correlations between the dysregulation of sleep and the CSF orexin levels,” says Liguori. Patients with moderate to severe AD showed increased CSF orexin, and exhibited perturbed sleep patterns compared with the mild AD and control groups.
NATURE REVIEWS | NEUROLOGY
Moreover, the sleep deterioration— reduced deep sleep (N3) and rapid eye movement (REM) sleep, increased wakefulness after sleep onset, and decreased sleep quality—correlated with cognitive decline. “We hypothesize that in future, we could administer anti-orexin drugs at night to reduce the nocturnal wakefulness and improve sleep quality,” suggests Liguori. Sleep disruption has been proposed to exacerbate neurodegeneration in AD, so restoration of sleep rhythms—in particular, N3 and REM sleep—might slow down the progression of AD. Hemi Malkki Original article Liguori, C. et al. Orexinergic system dysregulation, sleep impairment, and cognitive decline in Alzheimer disease. JAMA Neurol. doi:10.1001/ jamaneurol.2014.2510 Further reading Videnovic, A. et al. ‘The clocks that time us’—circadian rhythms in neurodegenerative disorders. Nat. Rev. Neurol. doi:10.1038/nrneurol.2014.206
ADVANCE ONLINE PUBLICATION © 2014 Macmillan Publishers Limited. All rights reserved
ALZHEIMER DISEASE
Increased orexin level correlates with sleep disruption and cognitive decline in Alzheimer disease
Yen Teoh/Hemera/Thinkstock
Overactivation of the orexinergic system progresses in parallel with sleep impairment and cognitive decline in Alzheimer disease (AD), according to new research by Claudio Liguori and colleagues from the University of Rome Tor Vergata, Italy. Orexin increases arousal and maintains wakefulness, and dysregulation of orexinergic system might contribute to the
increased wakefulness after sleep onset that is observed in AD. This sleep disruption could result from imbalance between the cholinergic and orexinergic systems owing to cholinergic depletion, which is characteristic of advanced AD. Liguori and colleagues collected cerebrospinal fluid (CSF) samples from 48 patients with AD and 29 control participants, and analysed CSF levels of orexin and AD biomarkers, including amyloid-β1–42 and tau. The participants also underwent polysomnography and Mini Mental State Examination (MMSE). On the basis of MMSE scores, the patients were divided into groups with mild AD or moderate to severe AD. “We found intriguing correlations between the dysregulation of sleep and the CSF orexin levels,” says Liguori. Patients with moderate to severe AD showed increased CSF orexin, and exhibited perturbed sleep patterns compared with the mild AD and control groups.
NATURE REVIEWS | NEUROLOGY
Moreover, the sleep deterioration— reduced deep sleep (N3) and rapid eye movement (REM) sleep, increased wakefulness after sleep onset, and decreased sleep quality—correlated with cognitive decline. “We hypothesize that in future, we could administer anti-orexin drugs at night to reduce the nocturnal wakefulness and improve sleep quality,” suggests Liguori. Sleep disruption has been proposed to exacerbate neurodegeneration in AD, so restoration of sleep rhythms—in particular, N3 and REM sleep—might slow down the progression of AD. Hemi Malkki Original article Liguori, C. et al. Orexinergic system dysregulation, sleep impairment, and cognitive decline in Alzheimer disease. JAMA Neurol. doi:10.1001/ jamaneurol.2014.2510 Further reading Videnovic, A. et al. ‘The clocks that time us’—circadian rhythms in neurodegenerative disorders. Nat. Rev. Neurol. doi:10.1038/nrneurol.2014.206
ADVANCE ONLINE PUBLICATION © 2014 Macmillan Publishers Limited. All rights reserved
