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REM Sleep Behavior Disorder and Other Sleep Disturbances in Non-Alzheimer Dementias

  • Sleep and Neurodegenerative Disorders (Y-E Ju, Section Editor)
  • Published:
Current Sleep Medicine Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The study aimed to review recent updates of our understanding of REM sleep behavior disorder (RBD) and other sleep disorders in non-Alzheimer’s disease (AD) dementias.

Recent Findings

Numerous recent discoveries have provided insight into the role of RBD and sleep in patients with non-AD dementias. Imaging modalities such as DaTscan and cerebral blood flow may be useful for monitoring phenoconversion in idiopathic RBD patients to Parkinson’s disease (PD) or dementia with Lewy bodies (DLB). Patients with isolated REM sleep without atonia have non-motor signs of neurodegenerative disease. Colon mucosal biopsies in iRBD patients have shown presence of α-synuclein aggregates. Recent genetic models of RBD and neuroimaging have furthered evidence for the locus subcoeruleus/sublateral dorsal nucleus as the center for the generation and maintenance of REM muscle atonia. Circadian rhythm disturbances likely play a large role in nighttime insomnia, daytime sleepiness, autonomic symptoms, motor variations, and hallucinations in PD and DLB. Early onset stridor in patients with multiple system atrophy (MSA) portends a worse prognosis than late onset stridor, and treatment of stridor is associated with survival.

Summary

Our ability to predict phenoconversion in idiopathic RBD is improving and will be highly important as “high risk” phenoconverters are identified for enrollment in neuroprotective clinical trials. Treatments of RBD improve but do not fully eliminate DEB; therefore, the risk for sleep-related injury remains a concern even among seemingly well-treated patients. Excessive daytime sleepiness (EDS) secondary to neuropathology, sedating medications, sleep disordered breathing (SDB), restless legs syndrome (RLS), and circadian rhythm alterations are common in the non-AD dementias, leading to significant caregiver burden and worsening of cognition. Addressing primary sleep disorders is the mainstay of treatment for EDS. RLS is a frequent co-morbidity in non-AD dementias. Initial management of RLS includes ensuring serum a ferritin level of >75 μg/L and therapy with gabapentin encarbil (which is less likely to cause augmentation than dopamine agonists). All MSA patients should be evaluated for the presence of nocturnal stridor, which should be treated if present. Therapies targeting the circadian system are often an underutilized therapeutic avenue in the management of sleep, motor, autonomic, and psychiatric symptoms in PD and DLB patients.

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References

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

  1. Tsuboi Y, Dickson DW. Dementia with Lewy bodies and Parkinson's disease with dementia: are they different? Parkinsonism Relat Disord. 2005;11(Suppl 1):S47–51.

    Article  PubMed  Google Scholar 

  2. McKeith IG, Dickson DW, Lowe J, Emre M, O'Brien JT, Feldman H, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology. 2005;65(12):1863–72.

    Article  CAS  PubMed  Google Scholar 

  3. Brown RG, Lacomblez L, Landwehrmeyer BG, Bak T, Uttner I, Dubois B, et al. Cognitive impairment in patients with multiple system atrophy and progressive supranuclear palsy. Brain. 2010;133(Pt 8):2382–93.

    Article  PubMed  Google Scholar 

  4. 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(11):1006–14.

    Article  PubMed  PubMed Central  Google Scholar 

  5. 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(7):858–81.

    Article  PubMed  Google Scholar 

  6. 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(1):50–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Bliwise DL, Mercaldo ND, Avidan AY, Boeve BF, Greer SA, Kukull WA. Sleep disturbance in dementia with Lewy bodies and Alzheimer's disease: a multicenter analysis. Dement Geriatr Cogn Disord. 2011;31(3):239–46.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Rongve A, Boeve BF, Aarsland D. Frequency and correlates of caregiver-reported sleep disturbances in a sample of persons with early dementia. J am Geriatr Soc. 2010;58(3):480–6.

    Article  PubMed  Google Scholar 

  9. • McCarter SJ, St Louis EK, Boeve BF. Sleep disturbances in frontotemporal dementia. Curr Neurol Neurosci Rep. 2016;16(9):85. This comprehensive review of sleep disorders in frontotemporal dementia discusses sleep disorders commonly seen in frontotemporal dementia, their impact on cognition, and treatments commonly employed in dementia patients with disordered sleep.

    Article  PubMed  Google Scholar 

  10. Schenck CH, Bundlie SR, Ettinger MG, Mahowald MW. Chronic behavioral disorders of human REM sleep: a new category of parasomnia. Sleep. 1986;9(2):293–308.

    Article  CAS  PubMed  Google Scholar 

  11. Wing YK, Lam SP, Li SX, Yu MW, Fong SY, Tsoh JM, et al. REM sleep behaviour disorder in Hong Kong Chinese: clinical outcome and gender comparison. J Neurol Neurosurg Psychiatry. 2008;79(12):1415–6.

    Article  CAS  PubMed  Google Scholar 

  12. Olson EJ, Boeve BF, Silber MH. Rapid eye movement sleep behaviour disorder: demographic, clinical and laboratory findings in 93 cases. Brain. 2000;123(Pt 2):331–9.

    Article  PubMed  Google Scholar 

  13. Schenck CH, Mahowald MW. A polysomnographic, neurologic, psychiatric and clinical outcome report on 70 consecutive cases with REM sleep behavior disorder (RBD): sustained clonazepam efficacy in 89.5% of 57 treated patients. Clev Clin J Med. 1990;57(Suppl):10–24.

    Google Scholar 

  14. •• Fernandez-Arcos A, Iranzo A, Serradell M, Gaig C, Santamaria J. The clinical phenotype of idiopathic rapid eye movement sleep behavior disorder at presentation: a study in 203 consecutive patients. Sleep. 2016;39(1):121–32. This large cohort study of idiopathic RBD patients describes the clinical phenotype of RBD patients, as well as response to treatment, non-motor signs of neurodegeneration and other demographic and clinical factors that have not been previously been reported in great detail.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Bodkin CL, Schenck CH. Rapid eye movement sleep behavior disorder in women: relevance to general and specialty medical practice. J Women's Health (Larchmt). 2009;18(12):1955–63.

    Article  Google Scholar 

  16. Chiu HF, Wing YK, Lam LC, Li SW, Lum CM, Leung T, et al. Sleep-related injury in the elderly—an epidemiological study in Hong Kong. Sleep. 2000;23(4):513–7.

    Article  CAS  PubMed  Google Scholar 

  17. Ohayon MM, Schenck CH. Violent behavior during sleep: prevalence, comorbidity and consequences. Sleep med. 2010;11(9):941–6.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kang SH, Yoon IY, Lee SD, Han JW, Kim TH, Kim KW. REM sleep behavior disorder in the Korean elderly population: prevalence and clinical characteristics. Sleep. 2013;36(8):1147–52.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Boot BP, Boeve BF, Roberts RO, Ferman TJ, Geda YE, Pankratz VS, et al. Probable rapid eye movement sleep behavior disorder increases risk for mild cognitive impairment and Parkinson disease: a population-based study. Ann Neurol. 2012;71(1):49–56.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Dauvilliers Y, Postuma RB, Ferini-Strambi L, Arnulf I, Hogl B, Manni R, et al. Family history of idiopathic REM behavior disorder: a multicenter case-control study. Neurology. 2013;80(24):2233–5.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Gan-Or Z, Mirelman A, Postuma RB, Arnulf I, Bar-Shira A, Dauvilliers Y, et al. GBA mutations are associated with rapid eye movement sleep behavior disorder. Ann Clin Transl Neurol. 2015;2(9):941–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Postuma RB, Montplaisir JY, Pelletier A, Dauvilliers Y, Oertel W, Iranzo A, et al. Environmental risk factors for REM sleep behavior disorder: a multicenter case-control study. Neurology. 2012;79(5):428–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Boeve BF, Silber MH, Saper CB, Ferman TJ, Dickson DW, Parisi JE, et al. Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. Brain. 2007;130(Pt 11):2770–88.

    Article  CAS  PubMed  Google Scholar 

  24. Frauscher B, Gschliesser V, Brandauer E, Marti I, Furtner MT, Ulmer H, et al. REM sleep behavior disorder in 703 sleep-disorder patients: the importance of eliciting a comprehensive sleep history. Sleep Med. 2010;11(2):167–71.

    Article  PubMed  Google Scholar 

  25. Montplaisir J, Gagnon JF, Fantini ML, Postuma RB, Dauvilliers Y, Desautels A, et al. Polysomnographic diagnosis of idiopathic REM sleep behavior disorder. Mov Disord. 2010;25(13):2044–51.

    Article  PubMed  Google Scholar 

  26. Howell MJ, Schenck CH. Rapid eye movement sleep behavior disorder and neurodegenerative disease. JAMA Neurol. 2015;72(6):707–12.

    Article  PubMed  Google Scholar 

  27. Figorilli M, Ferri R, Zibetti M, Beudin P, Puligheddu M, Lopiano L, et al. Comparison between automatic and visual scorings of REM sleep without atonia for the diagnosis of REM sleep behavior disorder in Parkinson disease. Sleep. 2016.

  28. Claassen DO, Josephs KA, Ahlskog JE, Silber MH, Tippmann-Peikert M, Boeve BF. REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century. Neurology. 2010;75(6):494–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Iranzo A, Fernandez-Arcos A, Tolosa E, Serradell M, Molinuevo JL, Valldeoriola F, et al. Neurodegenerative disorder risk in idiopathic REM sleep behavior disorder: study in 174 patients. PLoS One. 2014;9(2):e89741.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Iranzo A, Lomena F, Stockner H, Valldeoriola F, Vilaseca I, Salamero M, et al. Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study [corrected]. Lancet Neurol. 2010;9(11):1070–7.

    Article  CAS  PubMed  Google Scholar 

  31. Iranzo A, Molinuevo JL, Santamaria J, Serradell M, Marti MJ, Valldeoriola F, et al. Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol. 2006;5(7):572–7.

    Article  PubMed  Google Scholar 

  32. Boeve BF, Silber MH, Ferman TJ. Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients. Sleep med. 2003;4(4):281–4.

    Article  PubMed  Google Scholar 

  33. Postuma RB, Gagnon JF, Rompre S, Montplaisir JY. Severity of REM atonia loss in idiopathic REM sleep behavior disorder predicts Parkinson disease. Neurology. 2010;74(3):239–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Sixel-Doring F, Trautmann E, Mollenhauer B, Trenkwalder C. Associated factors for REM sleep behavior disorder in Parkinson disease. Neurology. 2011;77(11):1048–54.

    Article  PubMed  CAS  Google Scholar 

  35. Schenck CH, Boeve BF, Mahowald MW. Delayed emergence of a parkinsonian disorder or dementia in 81% of older males initially diagnosed with idiopathic REM sleep behavior disorder (RBD): 16 year update on a previously reported series. Sleep med. 2013;

  36. Boeve BF, Silber MH, Ferman TJ, Lin SC, Benarroch EE, Schmeichel AM, et al. Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder. Sleep med. 2013;

  37. Iranzo A, Tolosa E, Gelpi E, Molinuevo JL, Valldeoriola F, Serradell M, et al. Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study. Lancet Neurol. 2013;12(5):443–53.

    Article  PubMed  Google Scholar 

  38. Medicine AAoS. International classification of sleep disorders, 3rd edition: diagnostic and coding manual. 3rd ed2014.

  39. 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(11):1332–8.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Uguccioni G, Golmard JL, de Fontreaux AN, Leu-Semenescu S, Brion A, Arnulf I. Fight or flight? Dream content during sleepwalking/sleep terrors vs. rapid eye movement sleep behavior disorder. Sleep med. 2013;14(5):391–8.

    Article  PubMed  Google Scholar 

  41. Valli K, Frauscher B, Gschliesser V, Wolf E, Falkenstetter T, Schonwald SV, et al. Can observers link dream content to behaviours in rapid eye movement sleep behaviour disorder? A cross-sectional experimental pilot study. J Sleep res. 2012;21(1):21–9.

    Article  PubMed  Google Scholar 

  42. McCarter S, St. Louis E, Boswell C, Dueffert L, Slocumb N, Boeve B, et al. Factors associated with injury in REM sleep behavior disorder. Sleep Med. 2014;In Press.

  43. Boeve BF, Molano JR, Ferman TJ, Smith GE, Lin SC, Bieniek K, et al. Validation of the Mayo Sleep Questionnaire to screen for REM sleep behavior disorder in an aging and dementia cohort. Sleep med. 2011;12(5):445–53.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Li SX, Wing YK, Lam SP, Zhang J, Yu MW, Ho CK, et al. Validation of a new REM sleep behavior disorder questionnaire (RBDQ-HK). Sleep med. 2010;11(1):43–8.

    Article  CAS  PubMed  Google Scholar 

  45. Postuma RB, Arnulf I, Hogl B, Iranzo A, Miyamoto T, Dauvilliers Y, et al. A single-question screen for rapid eye movement sleep behavior disorder: a multicenter validation study. Mov Disord. 2012;27(7):913–6.

    Article  PubMed  PubMed Central  Google Scholar 

  46. McCarter S, St. Louis E, Sandness D, Arndt K, Erickson M, Tabatabai G, et al. Antidepressants increase REM sleep muscle tone in patients with and without REM sleep behavior disorder sleep. 2014;In Press.

  47. • Stefani A, Gabelia D, Hogl B, Mitterling T, Mahlknecht P, Stockner H, et al. Long-term follow-up investigation of isolated rapid eye movement sleep without atonia without rapid eye movement sleep behavior disorder: a pilot study. J Clin Sleep med. 2015;11(11):1273–9. This study is the first to report the presence of subtle neurologic symptoms suggestive of neurodegenerative disease in patients with isolated REM sleep without atonia.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Postuma RB, Gagnon JF, Vendette M, Fantini ML, Massicotte-Marquez J, Montplaisir J. Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder. Neurology. 2009;72(15):1296–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Fantini ML, Postuma RB, Montplaisir J, Ferini-Strambi L. Olfactory deficit in idiopathic rapid eye movements sleep behavior disorder. Brain Res Bull. 2006;70(4–6):386–90.

    Article  PubMed  Google Scholar 

  50. Postuma RB, Gagnon JF, Vendette M, Montplaisir JY. Markers of neurodegeneration in idiopathic rapid eye movement sleep behaviour disorder and Parkinson's disease. Brain. 2009;132(Pt 12):3298–307.

    Article  CAS  PubMed  Google Scholar 

  51. •• Postuma RB, Gagnon JF, Vendette M, Desjardins C, Montplaisir JY. Olfaction and color vision identify impending neurodegeneration in rapid eye movement sleep behavior disorder. Ann Neurol. 2011;69(5):811–8. This article discusses the importance of RBD as a prodromal neurodegenerative disease and identifies a schema for identifying idiopathic RBD patients who will develop a clinical neurodegenerative syndrome within 3 years.

    Article  PubMed  Google Scholar 

  52. Postuma RB, Gagnon JF, Bertrand JA, Genier Marchand D, Montplaisir JY. Parkinson risk in idiopathic REM sleep behavior disorder: preparing for neuroprotective trials. Neurology. 2015;84(11):1104–13.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Mahlknecht P, Iranzo A, Hogl B, Frauscher B, Muller C, Santamaria J, et al. Olfactory dysfunction predicts early transition to a Lewy body disease in idiopathic RBD. Neurology. 2015;84(7):654–8.

    Article  PubMed  Google Scholar 

  54. Postuma RB, Iranzo A, Hogl B, Arnulf I, Ferini-Strambi L, Manni R, et al. Risk factors for neurodegeneration in idiopathic rapid eye movement sleep behavior disorder: a multicenter study. Ann Neurol. 2015;77(5):830–9.

    Article  PubMed  Google Scholar 

  55. Ferini-Strambi L, Oertel W, Dauvilliers Y, Postuma RB, Marelli S, Iranzo A, et al. Autonomic symptoms in idiopathic REM behavior disorder: a multicentre case-control study. J Neurol. 2014;261(6):1112–8.

    Article  PubMed  Google Scholar 

  56. Anang JB, Nomura T, Romenets SR, Nakashima K, Gagnon JF, Postuma RB. Dementia predictors in Parkinson disease: a validation study. J Parkinsons dis. 2016;

  57. Manni R, Sinforiani E, Pacchetti C, Zucchella C, Cremascoli R, Terzaghi M. Cognitive dysfunction and REM sleep behavior disorder: key findings in the literature and preliminary longitudinal findings. Int J Psychophysiol. 2013;

  58. Marchand DG, Montplaisir J, Postuma RB, Rahayel S, Gagnon JF. Detecting the cognitive prodrome of dementia with Lewy bodies: a prospective study of REM sleep behavior disorder. Sleep. 2016;

  59. Massicotte-Marquez J, Decary A, Gagnon JF, Vendette M, Mathieu A, Postuma RB, et al. Executive dysfunction and memory impairment in idiopathic REM sleep behavior disorder. Neurology. 2008;70(15):1250–7.

    Article  CAS  PubMed  Google Scholar 

  60. Iranzo A, Valldeoriola F, Lomena F, Molinuevo JL, Serradell M, Salamero M, et al. Serial dopamine transporter imaging of nigrostriatal function in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study. Lancet Neurol. 2011;10(9):797–805.

    Article  CAS  PubMed  Google Scholar 

  61. •• Heller J, Brcina N, Dogan I, Holtbernd F, Romanzetti S, Schulz JB, et al. Brain imaging findings in idiopathic REM sleep behavior disorder (RBD)—a systematic review on potential biomarkers for neurodegeneration. Sleep Med Rev. 2016. This systematic review examines the neuroimaging techniques available in idiopathic RBD and identifies which techniques may be useful biomarkers for phenoconversion in RBD patients.

  62. Vilas D, Iranzo A, Tolosa E, Aldecoa I, Berenguer J, Vilaseca I, et al. Assessment of alpha-synuclein in submandibular glands of patients with idiopathic rapid-eye-movement sleep behaviour disorder: a case-control study. Lancet Neurol. 2016;15(7):708–18.

    Article  CAS  PubMed  Google Scholar 

  63. Sprenger FS, Stefanova N, Gelpi E, Seppi K, Navarro-Otano J, Offner F, et al. Enteric nervous system alpha-synuclein immunoreactivity in idiopathic REM sleep behavior disorder. Neurology. 2015;85(20):1761–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Shannon KM, Keshavarzian A, Dodiya HB, Jakate S, Kordower JH. Is alpha-synuclein in the colon a biomarker for premotor Parkinson's disease? Evidence from 3 cases. Mov Disord. 2012;27(6):716–9.

    Article  PubMed  Google Scholar 

  65. Pao WC, Boeve BF, Ferman TJ, Lin SC, Smith GE, Knopman DS, et al. Polysomnographic findings in dementia with Lewy bodies. Neurologist. 2013;19(1):1–6.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Ferman TJ, Boeve BF, Smith GE, Lin SC, Silber MH, Pedraza O, et al. Inclusion of RBD improves the diagnostic classification of dementia with Lewy bodies. Neurology. 2011;77(9):875–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Dugger BN, Boeve BF, Murray ME, Parisi JE, Fujishiro H, Dickson DW, et al. Rapid eye movement sleep behavior disorder and subtypes in autopsy-confirmed dementia with Lewy bodies. Mov Disord. 2012;27(1):72–8.

    Article  PubMed  Google Scholar 

  68. Palma JA, Fernandez-Cordon C, Coon EA, Low PA, Miglis MG, Jaradeh S, et al. Prevalence of REM sleep behavior disorder in multiple system atrophy: a multicenter study and meta-analysis. Clin Auton res. 2015;25(1):69–75.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Dickson DW. Parkinson's disease and parkinsonism: neuropathology. Cold Spring Harb Perspect Med. 2012;2(8).

  70. Stanzani-Maserati M, Gallassi R, Calandra-Buonaura G, Alessandria M, Oppi F, Poda R, et al. Cognitive and sleep features of multiple system atrophy: review and prospective study. Eur Neurol. 2014;72(5–6):349–59.

    Article  PubMed  Google Scholar 

  71. Singer W, Berini SE, Sandroni P, Fealey RD, Coon EA, Suarez MD, et al. Pure autonomic failure: predictors of conversion to clinical CNS involvement. Neurology. 2017;88(12):1129–36.

    Article  PubMed  Google Scholar 

  72. 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(2):371–3.

    Article  PubMed  Google Scholar 

  73. Wang P, Wing YK, Xing J, Liu Y, Zhou B, Zhang Z, et al. Rapid eye movement sleep behavior disorder in patients with probable Alzheimer's disease. Aging Clin Exp res. 2016;28(5):951–7.

    Article  PubMed  Google Scholar 

  74. 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(10):1321–5.

    Article  PubMed  Google Scholar 

  75. Jouvet M, Delorme F. Locus coeruleus et sommeil paradoxal. C R Soc Biol. 1965;159:895–9.

    Google Scholar 

  76. Fraigne JJ, Torontali ZA, Snow MB, Peever JH. REM sleep at its core—circuits, neurotransmitters, and pathophysiology. Front Neurol. 2015;6:123.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Luppi PH, Clement O, Fort P. Paradoxical (REM) sleep genesis by the brainstem is under hypothalamic control. Curr Opin Neurobiol. 2013;23(5):786–92.

    Article  CAS  PubMed  Google Scholar 

  78. McCarter SJ, Tippmann-Peikert M, Sandness DJ, Flanagan EP, Kantarci K, Boeve BF, et al. Neuroimaging-evident lesional pathology associated with REM sleep behavior disorder. Sleep Med. 2015;16(12):1502–10.

    Article  PubMed  Google Scholar 

  79. Ehrminger M, Latimier A, Pyatigorskaya N, Garcia-Lorenzo D, Leu-Semenescu S, Vidailhet M, et al. The coeruleus/subcoeruleus complex in idiopathic rapid eye movement sleep behaviour disorder. Brain. 2016;139(Pt 4):1180–8.

    Article  PubMed  Google Scholar 

  80. Garcia-Lorenzo D, Longo-Dos Santos C, Ewenczyk C, Leu-Semenescu S, Gallea C, Quattrocchi G, et al. The coeruleus/subcoeruleus complex in rapid eye movement sleep behaviour disorders in Parkinson's disease. Brain. 2013;136(Pt 7):2120–9.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Iranzo A, Graus F, Clover L, Morera J, Bruna J, Vilar C, et al. Rapid eye movement sleep behavior disorder and potassium channel antibody-associated limbic encephalitis. Ann Neurol. 2006;59(1):178–81.

    Article  PubMed  Google Scholar 

  82. Luppi PH, Clement O, Valencia Garcia S, Brischoux F, Fort P. New aspects in the pathophysiology of rapid eye movement sleep behavior disorder: the potential role of glutamate, gamma-aminobutyric acid, and glycine. Sleep med. 2013;

  83. Valencia Garcia S, Libourel PA, Lazarus M, Grassi D, Luppi PH, Fort P. Genetic inactivation of glutamate neurons in the rat sublaterodorsal tegmental nucleus recapitulates REM sleep behaviour disorder. Brain. 2017;140(Pt 2):414–28.

    Article  PubMed  Google Scholar 

  84. Brooks PL, Peever JH. Identification of the transmitter and receptor mechanisms responsible for REM sleep paralysis. J Neurosci. 2012;32(29):9785–95.

    Article  CAS  PubMed  Google Scholar 

  85. Braak H, Ghebremedhin E, Rub U, Bratzke H, Del Tredici K. Stages in the development of Parkinson's disease-related pathology. Cell Tissue res. 2004;318(1):121–34.

    Article  PubMed  Google Scholar 

  86. Howell MJ, Arneson PA, Schenck CH. A novel therapy for REM sleep behavior disorder (RBD). J Clin Sleep med. 2011;7(6):639–44A.

    PubMed  PubMed Central  Google Scholar 

  87. Iranzo A, Santamaria J. Severe obstructive sleep apnea/hypopnea mimicking REM sleep behavior disorder. Sleep. 2005;28(2):203–6.

    Article  PubMed  Google Scholar 

  88. McCarter S, St. Louis E, Duwell E, Timm P, Sandness D, Boeve B, et al. Diagnostic thresholds for quantitative REM sleep phasic burst duration, phasic and tonic muscle activity, and REM atonia index in REM sleep behavior disorder with and without comorbid obstructive sleep apnea. Sleep. 2014;37(10):1649–62.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Kunz D, Bes F. Melatonin as a therapy in REM sleep behavior disorder patients: an open-labeled pilot study on the possible influence of melatonin on REM-sleep regulation. Mov Disord. 1999;14(3):507–11.

    Article  CAS  PubMed  Google Scholar 

  90. Kunz D, Mahlberg R. A two-part, double-blind, placebo-controlled trial of exogenous melatonin in REM sleep behaviour disorder. J Sleep res. 2010;19(4):591–6.

    Article  PubMed  Google Scholar 

  91. 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(3):237–42.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Li SX, Lam SP, Zhang J, Yu MW, Chan JW, Liu Y, et al. A prospective, naturalistic follow-up study of treatment outcomes with clonazepam in rapid eye movement sleep behavior disorder. Sleep med. 2016;21:114–20.

    Article  PubMed  Google Scholar 

  93. Bonakis A, Howard RS, Ebrahim IO, Merritt S, Williams A. REM sleep behaviour disorder (RBD) and its associations in young patients. Sleep med. 2009;10(6):641–5.

    Article  PubMed  Google Scholar 

  94. Lapierre O, Montplaisir J. Polysomnographic features of REM sleep behavior disorder: development of a scoring method. Neurology. 1992;42(7):1371–4.

    Article  CAS  PubMed  Google Scholar 

  95. Wing YK, Li SX, Mok V, Lam SP, Tsoh J, Chan A, et al. Prospective outcome of rapid eye movement sleep behaviour disorder: psychiatric disorders as a potential early marker of Parkinson's disease. J Neurol Neurosurg Psychiatry. 2012;83(4):470–2.

    Article  PubMed  Google Scholar 

  96. Ferri R, Marelli S, Ferini-Strambi L, Oldani A, Colli F, Schenck CH, et al. An observational clinical and video-polysomnographic study of the effects of clonazepam in REM sleep behavior disorder. Sleep med. 2013;14(1):24–9.

    Article  PubMed  Google Scholar 

  97. Schenck CH, Mahowald MW. Long-term, nightly benzodiazepine treatment of injurious parasomnias and other disorders of disrupted nocturnal sleep in 170 adults. Am J med. 1996;100(3):333–7.

    Article  CAS  PubMed  Google Scholar 

  98. Takeuchi N, Uchimura N, Hashizume Y, Mukai M, Etoh Y, Yamamoto K, et al. Melatonin therapy for REM sleep behavior disorder. Psychiatry Clin Neurosci. 2001;55(3):267–9.

    Article  CAS  PubMed  Google Scholar 

  99. Anderson KN, Shneerson JM. Drug treatment of REM sleep behavior disorder: the use of drug therapies other than clonazepam. J Clin Sleep med. 2009;5(3):235–9.

    PubMed  PubMed Central  Google Scholar 

  100. Arnaldi D, Latimier A, Leu-Semenescu S, Vidailhet M, Arnulf I. Loss of REM sleep features across nighttime in REM sleep behavior disorder. Sleep med. 2016;17:134–7.

    Article  PubMed  Google Scholar 

  101. Erland LA, Saxena PK. Melatonin natural health products and supplements: presence of serotonin and significant variability of melatonin content. J Clin Sleep med. 2017;13(2):275–81.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Esaki Y, Kitajima T, Koike S, Fujishiro H, Iwata Y, Tsuchiya A, et al. An open-labeled trial of Ramelteon in idiopathic rapid eye movement sleep behavior disorder. J Clin Sleep med. 2016;12(5):689–93.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Fantini ML, Gagnon JF, Filipini D, Montplaisir J. The effects of pramipexole in REM sleep behavior disorder. Neurology. 2003;61(10):1418–20.

    Article  CAS  PubMed  Google Scholar 

  104. Kumru H, Iranzo A, Carrasco E, Valldeoriola F, Marti MJ, Santamaria J, et al. Lack of effects of pramipexole on REM sleep behavior disorder in Parkinson disease. Sleep. 2008;31(10):1418–21.

    PubMed  PubMed Central  Google Scholar 

  105. Schmidt MH, Koshal VB, Schmidt HS. Use of pramipexole in REM sleep behavior disorder: results from a case series. Sleep med. 2006;7(5):418–23.

    Article  PubMed  Google Scholar 

  106. 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(2):153–7.

    Article  PubMed  Google Scholar 

  107. Massironi G, Galluzzi S, Frisoni GB. Drug treatment of REM sleep behavior disorders in dementia with Lewy bodies. Int Psychogeriatr. 2003;15(4):377–83.

    Article  PubMed  Google Scholar 

  108. Ringman JM, Simmons JH. Treatment of REM sleep behavior disorder with donepezil: a report of three cases. Neurology. 2000;55(6):870–1.

    Article  CAS  PubMed  Google Scholar 

  109. Ferman TJ, Smith GE, Dickson DW, Graff-Radford NR, Lin SC, Wszolek Z, et al. Abnormal daytime sleepiness in dementia with Lewy bodies compared to Alzheimer's disease using the Multiple Sleep Latency Test. Alzheimers res Ther. 2014;6(9):76.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Thannickal TC, Lai YY, Siegel JM. Hypocretin (orexin) cell loss in Parkinson's disease. Brain. 2007;130(Pt 6):1586–95.

    Article  PubMed  Google Scholar 

  111. Videnovic A, Noble C, Reid KJ, Peng J, Turek FW, Marconi A, et al. Circadian melatonin rhythm and excessive daytime sleepiness in Parkinson disease. JAMA Neurol. 2014;71(4):463–9.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Boeve BF. Update on the diagnosis and management of sleep disturbances in dementia. Sleep med Clin. 2008;3(3):347–60.

    Article  PubMed  PubMed Central  Google Scholar 

  113. Howcroft DJ, Jones RW. Does modafinil have the potential to improve disrupted sleep patterns in patients with dementia? Int J Geriatr Psychiatry. 2005;20(5):492–5.

    Article  CAS  PubMed  Google Scholar 

  114. St Louis EK. Key sleep neurologic disorders: narcolepsy, restless legs syndrome/Willis-Ekbom disease, and REM sleep behavior disorder. Neurol Clin Pract. 2014;4(1):16–25.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Winkelman JW, Armstrong MJ, Allen RP, Chaudhuri KR, Ondo W, Trenkwalder C, et al. Practice guideline summary: treatment of restless legs syndrome in adults: report of the guideline development, dissemination, and implementation Subcommittee of the American Academy of Neurology. Neurology. 2016;87(24):2585–93.

    Article  CAS  PubMed  Google Scholar 

  116. Moore TJ, Glenmullen J, Mattison DR. Reports of pathological gambling, hypersexuality, and compulsive shopping associated with dopamine receptor agonist drugs. JAMA Intern med. 2014;174(12):1930–3.

    Article  PubMed  Google Scholar 

  117. Videnovic A, Willis GL. Circadian system—a novel diagnostic and therapeutic target in Parkinson's disease? Mov Disord. 2016;31(3):260–9.

    Article  PubMed  PubMed Central  Google Scholar 

  118. Whitehead DL, Davies AD, Playfer JR, Turnbull CJ. Circadian rest-activity rhythm is altered in Parkinson's disease patients with hallucinations. Mov Disord. 2008;23(8):1137–45.

    Article  PubMed  Google Scholar 

  119. Anderson KN, Hatfield C, Kipps C, Hastings M, Hodges JR. Disrupted sleep and circadian patterns in frontotemporal dementia. Eur J Neurol. 2009;16(3):317–23.

    Article  CAS  PubMed  Google Scholar 

  120. 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(4):353–60.

    Article  CAS  PubMed  Google Scholar 

  121. Abbott SM, Videnovic A. Sleep disorders in atypical parkinsonism. Mov Disord Clin Pract. 2014;1(2):89–96.

    Article  PubMed  PubMed Central  Google Scholar 

  122. Giannini G, Calandra-Buonaura G, Mastrolilli F, Righini M, Bacchi-Reggiani ML, Cecere A, et al. Early stridor onset and stridor treatment predict survival in 136 patients with MSA. Neurology. 2016;87(13):1375–83.

    Article  PubMed  Google Scholar 

  123. Iranzo A, Santamaria J, Tolosa E, Vilaseca I, Valldeoriola F, Marti MJ, et al. Long-term effect of CPAP in the treatment of nocturnal stridor in multiple system atrophy. Neurology. 2004;63(5):930–2.

    Article  CAS  PubMed  Google Scholar 

  124. Shiba K, Isono S. Tracheostomy abolishes paradoxical activation of the vocal cord adductor in multiple system atrophy. Auris Nasus Larynx. 2006;33(3):295–8.

    Article  PubMed  Google Scholar 

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Correspondence to Michael J. Howell.

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Stuart J. McCarter declares no potential conflicts of interest.

Michael J. Howell is a co-owner of the Sleep Performance Institute.

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McCarter, S.J., Howell, M.J. REM Sleep Behavior Disorder and Other Sleep Disturbances in Non-Alzheimer Dementias. Curr Sleep Medicine Rep 3, 193–203 (2017). https://doi.org/10.1007/s40675-017-0078-z

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