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.
References
Ratnavalli E, Brayne C, Dawson K, Hodges JR (2002) The prevalence of frontotemporal dementia. Neurology 58(11):1615–1621
Neary D, Snowden J, Mann D (2005) Frontotemporal dementia. Lancet Neurol 4(11):771–780
Chare L, Hodges JR, Leyton CE, McGinley C, Tan RH, Kril JJ, Halliday GM (2014) New criteria for frontotemporal dementia syndromes: clinical and pathological diagnostic implications. J Neurol Neurosurg Psychiatry 85(8):865–870
Bonakis A, Economou NT, Paparrigopoulos T, Bonanni E, Maestri M, Carnicelli L et al (2014) Sleep in frontotemporal dementia is equally or possibly more disrupted, and at an earlier stage, when compared to sleep in Alzheimer’s disease. J Alzheimers Dis 38(1):85–91
Kundermann B, Thum A, Rocamora R, Haag A, Krieg JC, Hemmeter U (2011) Comparison of polysomnographic variables and their relationship to cognitive impairment in patients with Alzheimer’s disease and frontotemporal dementia. J Psychiatr Res 45(12):1585–1592
Anderson KN, Hatfield C, Kipps C, Hastings M, Hodges JR (2009) Disrupted sleep and circadian patterns in frontotemporal dementia. Eur J Neurol 16(3):317–323
Harper DG, Stopa EG, McKee AC, Satlin A, Harlan PC, Goldstein R, Volicer L (2001) Differential circadian rhythm disturbances in men with Alzheimer disease and frontotemporal degeneration. Arch Gen Psychiatry 58(4):353–360
Kanbayashi T, Sagawa Y, Takemura F, Ito SU, Tsutsui K, Hishikawa Y, Nishino S (2011) The pathophysiologic basis of secondary narcolepsy and hypersomnia. Curr Neurol Neurosci Rep 11(2):235–241
Kilduff TS, Peyron C (2000) The hypocretin/orexin ligand-receptor system: implications for sleep and sleep disorders. Trends Neurosci 23(8):359–365
Kirchgessner AL, Liu M (1999) Orexin synthesis and response in the gut. Neuron 24(4):941–951
Çoban A, Bilgiç B, Lohmann E, Küçükali Cİ, Benbir G, Karadeniz D et al (2013) Reduced orexin-A levels in frontotemporal dementia: possible association with sleep disturbance. Am J Alzheimers Dis Other Demen 28(6):606–611
Dalal MA, Schuld A, Haack M, Uhr M, Geisler P, Eisensehr I et al (2001) Normal plasma levels of orexin A (hypocretin-1) in narcoleptic patients. Neurology 56(12):1749–1751
Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ (1989) The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 28(2):193–213
Vignatelli L, Plazzi G, Barbato A, Ferini-Strambi L, Manni R, Pompei F et al (2003) Italian version of the Epworth sleepiness scale: external validity. Neurol Sci 23(6):295–300
Johns MW (1991) A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 14(6):540–545
Sancesario GM, Esposito Z, Nuccetelli M, Bernardini S, Sorge R, Martorana A et al (2010) Abeta1-42 detection in CSF of Alzheimer’s disease is influenced by temperature: indication of reversible Abeta1-42 aggregation? Exp Neurol 223(2):371–376
Liguori C, Placidi F, Albanese M, Nuccetelli M, Izzi F, Marciani MG et al (2014) CSF beta-amyloid levels are altered in narcolepsy: a link with the inflammatory hypothesis? J Sleep Res 23(4):420–424
Merlino G, Piani A, Gigli GL, Cancelli I, Rinaldi A, Baroselli A et al (2010) Daytime sleepiness is associated with dementia and cognitive decline in older Italian adults: a population-based study. Sleep Med 11(4):372–377
Saper CB, Chou TC, Scammell TE (2001) The sleep switch: hypothalamic control of sleep and wakefulness. Trends Neurosci 24(12):726–731
Piguet O, Petersén A, Yin Ka Lam B, Gabery S, Murphy K, Hodges JR, Halliday GM (2011) Eating and hypothalamus changes in behavioral-variant frontotemporal dementia. Ann Neurol 69(2):312–319
Engelborghs S, Maertens K, Vloeberghs E, Aerts T, Somers N, Mariën P, De Deyn PP (2006) Neuropsychological and behavioural correlates of CSF biomarkers in dementia. Neurochem Int 48(4):286–295
Grossman M, Farmer J, Leight S, Work M, Moore P, Van Deerlin V et al (2005) Cerebrospinal fluid profile in frontotemporal dementia and Alzheimer’s disease. Ann Neurol 57(5):721–729
Kapaki E, Paraskevas GP, Papageorgiou SG, Bonakis A, Kalfakis N, Zalonis I, Vassilopoulos D (2008) Diagnostic value of CSF biomarker profile in frontotemporal lobar degeneration. Alzheimer Dis Assoc Disord 22(1):47–53
Conflicts of interest
Claudio Liguori, Andrea Romigi, Nicola Biagio Mercuri, Giuseppe Sancesario, Alessandro Martorana, Maria Albanese, Francesca Izzi, Marzia Nuccetelli, Giulia Maria Sancesario, Maria Grazia Marciani, Sergio Bernardini, Fabio Placidi report no disclosures or conflict of interest.
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Liguori, C., Romigi, A., Mercuri, N.B. et al. Cerebrospinal-fluid orexin levels and daytime somnolence in frontotemporal dementia. J Neurol 261, 1832–1836 (2014). https://doi.org/10.1007/s00415-014-7455-z
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DOI: https://doi.org/10.1007/s00415-014-7455-z