RESEARCH HIGHLIGHTS
Nature Reviews Neurology 10, 672 (2014); published online 28 October 2014; doi:10.1038/nrneurol.2014.209
ALZHEIMER DISEASE
Increased orexin level correlates with sleep disruption
and cognitive decline in Alzheimer disease
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
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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.
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
VOLUME 10 | DECEMBER 2014