title: Cerebrospinal-fluid orexin levels and daytime somnolence in frontotemporal dementia.
abstract: Daytime somnolence and sleep-wake cycle disturbances are commonly encountered symptoms in Frontotemporal Dementia (FTD). Orexin-A (Hypocretin-1) is a hypothalamic neuropeptide regulating the sleep-wake rhythm. We investigated the cerebrospinal-fluid (CSF) orexin levels in a population of FTD patients and evaluated whether there is a relationship between daytime somnolence and CSF orexin concentrations. CSF orexin levels were measured in a sample of FTD patients (n = 11) compared to a population of non-demented controls (n = 13) similar for age and sex. Moreover, CSF orexin concentrations were correlated with daytime somnolence investigated by means of the Epworth Sleepiness Scale (ESS) in both FTD patients and controls. FTD patients showed CSF orexin concentrations (164.3 ± 66.45 vs 170.81 ± 42.73 pg/mL) and ESS scores (7.45 ± 4.36 vs 3.84 ± 1.82) not different from controls. However, three FTD patients showed pathological daytime sleepiness (ESS > 10) coupled with the lowest CSF orexin levels. In addition, we found a significant negative correlation between CSF orexin levels and ESS scores in the FTD population (R = -0.91; p < 0.0001), which was not evident in the control group (R = 0.16; p > 0.05). This is the first study investigating CSF orexin concentrations in FTD. We did not find differences in CSF orexin concentrations between FTD patients and controls. However, a significant negative correlation between daytime somnolence and CSF orexin levels was evident in FTD patients. Moreover, we have found that pathological daytime somnolence was evident in those FTD patients with the lowest CSF orexin levels. Based on these findings, we argued that lower orexin levels may be permissive for increased daytime somnolence in FTD.
authors.affiliation: Neurophysiopathology Unit, Department of Systems Medicine, Sleep Medicine Centre, University of Rome "Tor Vergata", Viale Oxford 81, 00133, Rome, Italy, dott.claudioliguori@yahoo.it.
authors.forename: C
authors.initials: C
authors.lastname: Liguori
authors.forename: A
authors.initials: A
authors.lastname: Romigi
authors.forename: N B
authors.initials: NB
authors.lastname: Mercuri
authors.forename: M
authors.initials: M
authors.lastname: Nuccetelli
authors.forename: F
authors.initials: F
authors.lastname: Izzi
authors.forename: M
authors.initials: M
authors.lastname: Albanese
authors.forename: G
authors.initials: G
authors.lastname: Sancesario
authors.forename: A
authors.initials: A
authors.lastname: Martorana
authors.forename: G M
authors.initials: GM
authors.lastname: Sancesario
authors.forename: S
authors.initials: S
authors.lastname: Bernardini
authors.forename: M G
authors.initials: MG
authors.lastname: Marciani
authors.forename: F
authors.initials: F
authors.lastname: Placidi
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D006970:Disorders of Excessive Somnolence / Q000209:etiology / Q000503:physiopathology*; D005260:Female; D057180:Frontotemporal Dementia / Q000134:cerebrospinal fluid* / Q000150:complications / Q000503:physiopathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D009479:Neuropeptides / Q000134:cerebrospinal fluid*; D000068797:Orexins; D012890:Sleep; D012894:Sleep Stages; D013223:Statistics as Topic
chemical_list: C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins