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Sleep Disturbances in Frontotemporal Dementia

Abstract

Sleep disorders appear to be frequent comorbidities in patients with frontotemporal dementia (FTD). Insomnia and excessive daytime sleepiness commonly occur in patients with FTD and significantly contribute to caregiver burden and burnout. Sleep is severely fragmented in FTD patients, likely secondary to behavioral disturbances, other primary sleep disorders such as sleep disordered breathing and restless leg syndrome, and neurodegeneration of nuclei involved in sleep and wakefulness. Treatment of primary sleep disorders may improve excessive daytime sleepiness and sleep quality and may improve daytime cognitive functioning. Rapid eye movement (REM) sleep behavior disorder is rare in FTD and may be confused with excessive nocturnal activity due to disturbed circadian rhythm. The relationship between FTD, sleep quality, and sleep disorders requires further study to better understand the contribution of disturbed sleep to daytime neurocognitive functioning and quality of life in FTD. Further, future studies should focus on comparing sleep disturbances between different FTD syndromes, especially behavioral variant FTD and primary progressive aphasia. Comorbid sleep disorders should be promptly sought and treated in patients with FTD to improve patient and caregiver quality of life.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance, •• Of major importance

  1. Onyike CU, Diehl-Schmid J. The epidemiology of frontotemporal dementia. Int Rev Psychiatry. 2013;25:130–7.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, et al. Classification of primary progressive aphasia and its variants. Neurology. 2011;76:1006–14.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Lashley T, Rohrer JD, Mead S, Revesz T. Review: an update on clinical, genetic and pathological aspects of frontotemporal lobar degenerations. Neuropathol Appl Neurobiol. 2015;41:858–81.

    Article  PubMed  Google Scholar 

  4. Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain. 2011;134:2456–77.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Warren JD, Rohrer JD, Rossor MN. Clinical review. Frontotemporal dementia. BMJ. 2013;347:f4827.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Johnson JK, Diehl J, Mendez MF, Neuhaus J, Shapira JS, Forman M, et al. Frontotemporal lobar degeneration: demographic characteristics of 353 patients. Arch Neurol. 2005;62:925–30.

    PubMed  Google Scholar 

  7. Miller MA. The role of sleep and sleep disorders in the development, diagnosis, and management of neurocognitive disorders. Front Neurol. 2015;6:224.

    PubMed  PubMed Central  Google Scholar 

  8. Chwiszczuk L, Breitve M, Hynninen M, Gjerstad MD, Aarsland D, Rongve A. Higher frequency and complexity of sleep disturbances in dementia with Lewy bodies as compared to Alzheimer’s disease. Neurodegener Dis. 2016;16(3–4):152–60.

  9. Raggi A, Neri W, Ferri R. Sleep-related behaviors in Alzheimer’s disease and dementia with Lewy bodies. Rev Neurosci. 2015;26:31–8.

    Article  PubMed  Google Scholar 

  10. Villa C, Ferini-Strambi L, Combi R. The synergistic relationship between Alzheimer’s disease and sleep disorders: an update. J Alzheimers Dis. 2015;46:571–80.

    Article  PubMed  Google Scholar 

  11. Anderson KN, Hatfield C, Kipps C, Hastings M, Hodges JR. Disrupted sleep and circadian patterns in frontotemporal dementia. Eur J Neurol. 2009;16:317–23.

    Article  CAS  PubMed  Google Scholar 

  12. Bonakis A, Economou NT, Paparrigopoulos T, Bonanni E, Maestri M, Carnicelli L, et al. 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. 2014;38:85–91. The authors of this article investigate sleep characteristics of patients with Alzheimer’s disease (AD) compared with frontotemporal dementia (FTD) through sleep quality surveys and video polysomnography. They found that patients with FTD have more severely disturbed sleep at an early stage of disease progression when compared to patients with AD, and that sleep characteristics might help differentiate between these two diseases. This is one of the few studies on sleep in FTD patients with PSG data.

    PubMed  Google Scholar 

  13. Bozeat S, Gregory CA, Ralph MA, Hodges JR. Which neuropsychiatric and behavioural features distinguish frontal and temporal variants of frontotemporal dementia from Alzheimer’s disease? J Neurol Neurosurg Psychiatry. 2000;69:178–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Coban A, Bilgic B, Lohmann E, Kucukali CI, Benbir G, Karadeniz D, et al. Reduced orexin-A levels in frontotemporal dementia: possible association with sleep disturbance. Am J Alzheimers Dis Other Demen. 2013;28:606–11.

    Article  PubMed  Google Scholar 

  15. Guarnieri B, Adorni F, Musicco M, Appollonio I, Bonanni E, Caffarra P, et al. Prevalence of sleep disturbances in mild cognitive impairment and dementing disorders: a multicenter Italian clinical cross-sectional study on 431 patients. Dement Geriatr Cogn Disord. 2012;33:50–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Harper DG, Stopa EG, McKee AC, Satlin A, Harlan PC, Goldstein R, et al. Differential circadian rhythm disturbances in men with Alzheimer disease and frontotemporal degeneration. Arch Gen Psychiatry. 2001;58:353–60.

    Article  CAS  PubMed  Google Scholar 

  17. Kundermann B, Thum A, Rocamora R, Haag A, Krieg JC, Hemmeter U. Comparison of polysomnographic variables and their relationship to cognitive impairment in patients with Alzheimer’s disease and frontotemporal dementia. J Psychiatr Res. 2011;45:1585–92.

    Article  PubMed  Google Scholar 

  18. Lo Coco D, Cupidi C, Mattaliano A, Baiamonte V, Realmuto S, Cannizzaro E. REM sleep behavior disorder in a patient with frontotemporal dementia. Neurol Sci. 2012;33:371–3.

    Article  PubMed  Google Scholar 

  19. Merrilees J, Hubbard E, Mastick J, Miller BL, Dowling GA. Sleep in persons with frontotemporal dementia and their family caregivers. Nurs Res. 2014;63:129–36.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Pawlak C, Blois R, Gaillard JM, Richard J. Sleep in Pick disease. Encephale. 1986;12:327–34.

    CAS  Google Scholar 

  21. Liu W, Miller BL, Kramer JH, Rankin K, Wyss-Coray C, Gearhart R, et al. Behavioral disorders in the frontal and temporal variants of frontotemporal dementia. Neurology. 2004;62:742–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hodges JR, Patterson K. Semantic dementia: a unique clinicopathological syndrome. Lancet Neurol. 2007;6:1004–14.

    Article  CAS  PubMed  Google Scholar 

  23. Mesulam M, Wieneke C, Rogalski E, Cobia D, Thompson C, Weintraub S. Quantitative template for subtyping primary progressive aphasia. Arch Neurol. 2009;66:1545–51.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Zhang Y, Tartaglia MC, Schuff N, Chiang GC, Ching C, Rosen HJ, et al. MRI signatures of brain macrostructural atrophy and microstructural degradation in frontotemporal lobar degeneration subtypes. J Alzheimers Dis. 2013;33:431–44.

    PubMed Central  Google Scholar 

  25. Gorno-Tempini ML, Dronkers NF, Rankin KP, Ogar JM, Phengrasamy L, Rosen HJ, et al. Cognition and anatomy in three variants of primary progressive aphasia. Ann Neurol. 2004;55:335–46.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Josephs KA, Whitwell JL, Knopman DS, Boeve BF, Vemuri P, Senjem ML, et al. Two distinct subtypes of right temporal variant frontotemporal dementia. Neurology. 2009;73:1443–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Seeley WW, Bauer AM, Miller BL, Gorno-Tempini ML, Kramer JH, Weiner M, et al. The natural history of temporal variant frontotemporal dementia. Neurology. 2005;64:1384–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Phukan J, Elamin M, Bede P, Jordan N, Gallagher L, Byrne S, et al. The syndrome of cognitive impairment in amyotrophic lateral sclerosis: a population-based study. J Neurol Neurosurg Psychiatry. 2012;83:102–8.

    Article  PubMed  Google Scholar 

  29. Boeve BF, Boylan KB, Graff-Radford NR, DeJesus-Hernandez M, Knopman DS, Pedraza O, et al. Characterization of frontotemporal dementia and/or amyotrophic lateral sclerosis associated with the GGGGCC repeat expansion in C9ORF72. Brain. 2012;135:765–83.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Ahmed RM, Newcombe RE, Piper AJ, Lewis SJ, Yee BJ, Kiernan MC, et al. Sleep disorders and respiratory function in amyotrophic lateral sclerosis. Sleep Med Rev. 2015;26:33–42.

    Article  PubMed  Google Scholar 

  31. Fernandez Martinez M, Castro Flores J, Perez de las Heras S, Mandaluniz Lekumberri A, Gordejuela Menocal M, Zarranz Imirizaldu JJ. Prevalence of neuropsychiatric symptoms in elderly patients with dementia in Mungialde County (Basque Country, Spain). Dement Geriatr Cogn Disord. 2008;25:103–8.

    Article  PubMed  Google Scholar 

  32. Srikanth S, Nagaraja AV, Ratnavalli E. Neuropsychiatric symptoms in dementia-frequency, relationship to dementia severity and comparison in Alzheimer’s disease, vascular dementia and frontotemporal dementia. J Neurol Sci. 2005;236:43–8.

    Article  CAS  PubMed  Google Scholar 

  33. Hodges JR, Davies RR, Xuereb JH, Casey B, Broe M, Bak TH, et al. Clinicopathological correlates in frontotemporal dementia. Ann Neurol. 2004;56:399–406.

    Article  PubMed  Google Scholar 

  34. Maestri M, Carnicelli L, Economou NT, Bonakis A, Paparrigopoulos T, Papageorgiou ST, et al. NREM sleep transient events in fronto-temporal dementia: beyond sleep stage architecture. Arch Ital Biol. 2015;153:226–36.

    Google Scholar 

  35. Bennett LS, Langford BA, Stradling JR, Davies RJ. Sleep fragmentation indices as predictors of daytime sleepiness and nCPAP response in obstructive sleep apnea. Am J Respir Crit Care Med. 1998;158:778–86.

    Article  CAS  PubMed  Google Scholar 

  36. Brooks D, Horner RL, Kimoff RJ, Kozar LF, Render-Teixeira CL, Phillipson EA. Effect of obstructive sleep apnea versus sleep fragmentation on responses to airway occlusion. Am J Respir Crit Care Med. 1997;155:1609–17.

    Article  CAS  PubMed  Google Scholar 

  37. Kimoff RJ. Sleep fragmentation in obstructive sleep apnea. Sleep. 1996;19:S61–6.

    CAS  PubMed  Google Scholar 

  38. Liguori C, Romigi A, Mercuri NB, Nuccetelli M, Izzi F, Albanese M, et al. Cerebrospinal-fluid orexin levels and daytime somnolence in frontotemporal dementia. J Neurol. 2014;261:1832–6. The authors of this article investigated levels of CSF orexin in patients with FTD and compared them with controls. While they found no differences in CSF orexin levels between the two groups, they did find a correlation between lower CSF orexin levels and increased report of sleepiness in patients with FTD, suggesting that alterations in orexin may contribute to sleepiness in FTD.

    Article  CAS  PubMed  Google Scholar 

  39. Singer C, Tractenberg RE, Kaye J, Schafer K, Gamst A, Grundman M, et al. A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer’s disease. Sleep. 2003;26:893–901.

    PubMed  PubMed Central  Google Scholar 

  40. Van Someren EJ, Kessler A, Mirmiran M, Swaab DF. Indirect bright light improves circadian rest-activity rhythm disturbances in demented patients. Biol Psychiatry. 1997;41:955–63.

    Article  Google Scholar 

  41. Yamakawa M, Shigenobu K, Makimoto K, Zhu C, Ashida N, Tabushi K. Environmental control interventions for frontotemporal dementia with reversed sleep-wake cycles. Am J Alzheimers Dis Other Demen. 2008;23:470–6.

    Article  PubMed  Google Scholar 

  42. Boeve BF. Update on the diagnosis and management of sleep disturbances in dementia. Sleep Med Clin. 2008;3:347–60.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Avlonitou E, Kapsimalis F, Varouchakis G, Vardavas CI, Behrakis P. Adherence to CPAP therapy improves quality of life and reduces symptoms among obstructive sleep apnea syndrome patients. Sleep Breath. 2012;16:563–9.

    Article  PubMed  Google Scholar 

  44. Gaig C, Iranzo A. Sleep-disordered breathing in neurodegenerative diseases. Curr Neurol Neurosci Rep. 2012;12:205–17.

    Article  PubMed  Google Scholar 

  45. Irfan M, Selim B, Rabinstein AA, St Louis EK. Neuromuscular disorders and sleep in critically ill patients. Crit Care Clin. 2015;31:533–50.

    Article  PubMed  Google Scholar 

  46. Osorio RS, Gumb T, Pirraglia E, Varga AW, Lu SE, Lim J, et al. Sleep-disordered breathing advances cognitive decline in the elderly. Neurology. 2015;84:1964–71.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Boeve BF. REM sleep behavior disorder: updated review of the core features, the REM sleep behavior disorder-neurodegenerative disease association, evolving concepts, controversies, and future directions. Ann N Y Acad Sci. 2010;1184:15–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Iranzo A, Santamaria J, Tolosa E. The clinical and pathophysiological relevance of REM sleep behavior disorder in neurodegenerative diseases. Sleep Med Rev. 2009;13:385–401.

    Article  PubMed  Google Scholar 

  49. McCarter SJ, St Louis EK, Boeve BF. REM sleep behavior disorder and REM sleep without atonia as an early manifestation of degenerative neurological disease. Curr Neurol Neurosci Rep. 2012;12:182–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Arnulf I, Merino-Andreu M, Bloch F, Konofal E, Vidailhet M, Cochen V, et al. REM sleep behavior disorder and REM sleep without atonia in patients with progressive supranuclear palsy. Sleep. 2005;28:349–54.

    PubMed  Google Scholar 

  51. Gagnon JF, Petit D, Fantini ML, Rompre S, Gauthier S, Panisset M, et al. REM sleep behavior disorder and REM sleep without atonia in probable Alzheimer disease. Sleep. 2006;29:1321–5.

    PubMed  Google Scholar 

  52. Daoud H, Postuma RB, Bourassa CV, Rochefort D, Gauthier MT, Montplaisir J, et al. C9orf72 repeat expansions in rapid eye movement sleep behaviour disorder. Can J Neurol Sci. 2014;41:759–62.

    Article  PubMed  Google Scholar 

  53. Majounie E, Renton AE, Mok K, Dopper EG, Waite A, Rollinson S, et al. Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. Lancet Neurol. 2012;11:323–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Claassen DO, Parisi JE, Giannini C, Boeve BF, Dickson DW, Josephs KA. Frontotemporal dementia mimicking dementia with Lewy bodies. Cogn Behav Neurol. 2008;21:157–63.

    Article  PubMed  Google Scholar 

  55. McCarter SJ, Boswell CL, St Louis EK, Dueffert LG, Slocumb N, Boeve BF, et al. Treatment outcomes in REM sleep behavior disorder. Sleep Med. 2013;14:237–42.

    Article  PubMed  PubMed Central  Google Scholar 

  56. McCarter SJ, St Louis EK, Boswell CL, Dueffert LG, Slocumb N, Boeve BF, et al. Factors associated with injury in REM sleep behavior disorder. Sleep Med. 2014;15:1332–8.

    Article  PubMed  PubMed Central  Google Scholar 

  57. McGrane IR, Leung JG, St Louis EK, Boeve BF. Melatonin therapy for REM sleep behavior disorder: a critical review of evidence. Sleep Med. 2015;16:19–26.

    Article  PubMed  Google Scholar 

  58. Brunetti V, Losurdo A, Testani E, Lapenta L, Mariotti P, Marra C, et al. Rivastigmine for refractory REM behavior disorder in mild cognitive impairment. Curr Alzheimer Res. 2014;11:267–73.

    Article  CAS  PubMed  Google Scholar 

  59. Di Giacopo R, Fasano A, Quaranta D, Della Marca G, Bove F, Bentivoglio AR. Rivastigmine as alternative treatment for refractory REM behavior disorder in Parkinson’s disease. Mov Disord. 2012;27:559–61.

    Article  PubMed  Google Scholar 

  60. Ringman JM, Simmons JH. Treatment of REM sleep behavior disorder with donepezil: a report of three cases. Neurology. 2000;55:870–1.

    Article  CAS  PubMed  Google Scholar 

  61. Sasai T, Matsuura M, Inoue Y. Factors associated with the effect of pramipexole on symptoms of idiopathic REM sleep behavior disorder. Parkinsonism Relat Disord. 2013;19:153–7.

    Article  PubMed  Google Scholar 

  62. Allen RP, Picchietti DL, Garcia-Borreguero D, Ondo WG, Walters AS, Winkelman JW, et al. Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria—history, rationale, description, and significance. Sleep Med. 2014;15:860–73.

    Article  PubMed  Google Scholar 

  63. Iranzo A, Comella CL, Santamaria J, Oertel W. Restless legs syndrome in Parkinson’s disease and other neurodegenerative diseases of the central nervous system. Mov Disord. 2007;22 Suppl 18:S424–30.

    Article  PubMed  Google Scholar 

  64. Limousin N, Blasco H, Corcia P, Arnulf I, Praline J. The high frequency of restless legs syndrome in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2011;12:303–6.

    Article  PubMed  Google Scholar 

  65. Allen RP, Adler CH, Du W, Butcher A, Bregman DB, Earley CJ. Clinical efficacy and safety of IV ferric carboxymaltose (FCM) treatment of RLS: a multi-centred, placebo-controlled preliminary clinical trial. Sleep Med. 2011;12:906–13.

    Article  PubMed  Google Scholar 

  66. Garcia-Borreguero D, Kohnen R, Silber MH, Winkelman JW, Earley CJ, Hogl B, et al. The long-term treatment of restless legs syndrome/Willis-Ekbom disease: evidence-based guidelines and clinical consensus best practice guidance: a report from the International Restless Legs Syndrome Study Group. Sleep Med. 2013;14:675–84.

    Article  PubMed  Google Scholar 

  67. Cornelius JR, Tippmann-Peikert M, Slocumb NL, Frerichs CF, Silber MH. Impulse control disorders with the use of dopaminergic agents in restless legs syndrome: a case-control study. Sleep. 2010;33:81–7.

    PubMed  PubMed Central  Google Scholar 

  68. Qaseem A, Holty JE, Owens DK, Dallas P, Starkey M, Shekelle P, et al. Management of obstructive sleep apnea in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2013;159:471–83.

    Article  PubMed  Google Scholar 

  69. Aurora RN, Zak RS, Maganti RK, Auerbach SH, Casey KR, Chowdhuri S, et al. Best practice guide for the treatment of REM sleep behavior disorder (RBD). J Clin Sleep Med. 2010;6:85–95.

    PubMed  PubMed Central  Google Scholar 

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Correspondence to Stuart J. McCarter.

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Stuart J. McCarter declares that he has no conflict of interest.

Erik K. St. Louis has received personal fees from Inspire, Inc.

Bradley F. Boeve has received personal fees from Scientific Advisory Board—Tau Consortium and Isis Pharmaceuticals. Dr. Boeve has also received grants from GE Healthcare, the NIH, Mangurian Foundation, Cephalon, Inc., FORUM Pharmaceuticals, and C2N Diagnostics.

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McCarter, S.J., St. Louis, E.K. & Boeve, B.F. Sleep Disturbances in Frontotemporal Dementia. Curr Neurol Neurosci Rep 16, 85 (2016). https://doi.org/10.1007/s11910-016-0680-3

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