title: Rapid eye movement sleep disruption and sleep fragmentation are associated with increased orexin-A cerebrospinal-fluid levels in mild cognitive impairment due to Alzheimer's disease.
abstract: The orexin system has been investigated in patients affected by mild cognitive impairment (MCI) due to Alzheimer's disease (AD) by measuring orexin-A concentrations in the cerebrospinal fluid (CSF), and correlated to subjective and objective sleep parameters, quantified by questionnaires and polysomnography, respectively. Twenty drug-naïve patients with MCI due to AD were studied and compared with a population of 26 age and/or sex matched controls, divided into subgroups on the basis of the Pittsburgh Sleep Quality Index (PSQI) score. Increased CSF-orexin levels were detected in patients with MCI due to AD in comparison with controls (p < 0.05). In particular, CSF-orexin concentrations were higher in MCI patients suffering from sleep complaints (PSQI ≥5, n = 10) compared with MCI patients with a regular sleep-wake cycle (PSQI <5, n = 10, p < 0.001) and compared with both control groups (with sleep complaints, PSQI ≥5, n = 11, p < 0.001; without sleep complaints, PSQI <5, n = 15, p < 0.001). Moreover, REM sleep was reduced in MCI patients compared with controls (p < 0.01), and had a negative correlation coupled with a reciprocal influence at the multiple regression analysis with CSF-orexin levels (R = -0.65; β = -8.90). REM sleep disruption and sleep fragmentation are related to higher CSF-orexin levels in patients with MCI due to AD, thus suggesting that the orexin system may be involved even in the earliest stages of AD, resulting in prolonged sleep latency, reduced sleep efficiency, and REM sleep impairment.
authors.affiliation: Sleep Medicine Centre, Neurophysiopathology Unit, Department of Systems Medicine, "Tor Vergata" University of Rome, Rome, Italy. Electronic address: dott.claudioliguori@yahoo.it.
authors.forename: Claudio
authors.initials: C
authors.lastname: Liguori
authors.affiliation: Clinical Biochemistry and Molecular Biology, "Tor Vergata" University of Rome, Rome, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Nuccetelli
authors.affiliation: Sleep Medicine Centre, Neurophysiopathology Unit, Department of Systems Medicine, "Tor Vergata" University of Rome, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Izzi
authors.affiliation: Neurology Unit, Department of Systems Medicine, "Tor Vergata" University of Rome, Rome, Italy; Fondazione Santa Lucia IRCCS, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sancesario
authors.affiliation: Sleep Medicine Centre, Neurophysiopathology Unit, Department of Systems Medicine, "Tor Vergata" University of Rome, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Romigi
authors.affiliation: Neurology Unit, Department of Systems Medicine, "Tor Vergata" University of Rome, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Martorana
authors.affiliation: Sleep Medicine Centre, Neurophysiopathology Unit, Department of Systems Medicine, "Tor Vergata" University of Rome, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Amoroso
authors.affiliation: Clinical Biochemistry and Molecular Biology, "Tor Vergata" University of Rome, Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernardini
authors.affiliation: Neurology Unit, Department of Systems Medicine, "Tor Vergata" University of Rome, Rome, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Marciani
authors.affiliation: Sleep Medicine Centre, Neurophysiopathology Unit, Department of Systems Medicine, "Tor Vergata" University of Rome, Rome, Italy; Fondazione Santa Lucia IRCCS, Rome, Italy.
authors.forename: Nicola Biagio
authors.initials: NB
authors.lastname: Mercuri
authors.affiliation: Sleep Medicine Centre, Neurophysiopathology Unit, Department of Systems Medicine, "Tor Vergata" University of Rome, Rome, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Placidi
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000150:complications* / Q000175:diagnosis; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D006801:Humans; D008297:Male; D000068797:Orexins / Q000134:cerebrospinal fluid*; D017286:Polysomnography; D012892:Sleep Deprivation / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000209:etiology*; D012893:Sleep Wake Disorders / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000209:etiology*; D012895:Sleep, REM
chemical_list: D015415:Biomarkers; D000068797:Orexins
keywords: Mild cognitive impairment due to Alzheimer's disease; Orexin; Polysomnography; REM sleep disruption; Subjective sleep disturbances