Skip to main content

Advertisement

SpringerLink
Log in

REM Sleep Behavior Disorder: a Prodromal Synucleinopathy

  • Neurology of Aging (K Marder, Section Editor)
  • Published:
Current Geriatrics Reports Aims and scope Submit manuscript

Abstract

Rapid eye movement sleep behavior disorder (RBD) is an abnormal condition that constitutes dream enactment behavior occurring during rapid eye movement (REM) phase sleep with loss of normal muscular atonia. Idiopathic RBD is a recognized risk factor for the development of alpha-synuclein neuropathology, often referred to as Lewy body disorders (LBD) like Parkinson disease, multiple system atrophy and dementia with Lewy bodies, with conversion rates of 80–90 % over a lifetime. In the past decade, studies have described multiple features of idiopathic RBD subjects that resemble patients with alpha-synucleinopathies, with specific abnormalities in olfaction, vision, gait, cognition, autonomic dysfunction, impaired cortical activity, and dopaminergic abnormalities in neuroimaging, leading to the idea that idiopathic RBD is a prodromal synucleinopathy that can precede neurodegenerative disease by decades.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

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

  1. Darien I. American Academy of Sleep Medicine. International classification of sleep disorders.3rd ed: American Academy of Sleep Medicine 2014.

  2. McCarter SJ, St Louis EK, Boswell CL, et al. Factors associated with injury in REM sleep behavior disorder. Sleep Med. 2014;15:1332–8.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Kang SH, Yoon IY, Lee SD, et al. REM sleep behavior disorder in the Korean elderly population: prevalence and clinical characteristics. Sleep. 2013;36:1147–52.

    PubMed  PubMed Central  Google Scholar 

  4. Boot BP, Boeve BF, Roberts RO, 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;71:49–56.

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. 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 

  7. Hsieh KC, Nguyen D, Siegel JM, Lai YY. New pathways and data on rapid eye movement sleep behaviour disorder in a rat model. Sleep Med. 2013;14:719–28.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Schenck CH, Boeve BF, Mahowald MW. Delayed emergence of a parkinsonian disorder or dementia in 81 % of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: a 16-year update on a previously reported series. Sleep Med. 2013;14:744–8.

    Article  PubMed  Google Scholar 

  9. Gagnon JF, Bedard MA, Fantini ML, et al. REM sleep behavior disorder and REM sleep without atonia in Parkinson’s disease. Neurology. 2002;59:585–9.

    Article  CAS  PubMed  Google Scholar 

  10. Plazzi G, Corsini R, Provini F, et al. REM sleep behavior disorders in multiple system atrophy. Neurology. 1997;48:1094–7.

    Article  CAS  PubMed  Google Scholar 

  11. Braak H, Ghebremedhin E, Rub U, et al. Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res. 2004;318:121–34.

    Article  PubMed  Google Scholar 

  12. Iranzo A, Molinuevo JL, Santamaria J, et al. Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol. 2006;5:572–7.

    Article  PubMed  Google Scholar 

  13. Postuma RB, Gagnon JF, Vendette M, et al. Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder. Neurology. 2009;72:1296–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256:183–94.

    Article  CAS  PubMed  Google Scholar 

  15. Aarsland D, Bronnick K, Larsen JP, et al. Cognitive impairment in incident, untreated Parkinson disease: the Norwegian ParkWest study. Neurology. 2009;72:1121–6.

    Article  CAS  PubMed  Google Scholar 

  16. Iranzo A, Tolosa E, Gelpi E, et al. Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study. Lancet Neurol. 2013;12:443–53. Definitive study that showed Lewy body disease present either clinically or with post-morten pathology in 97% of RBD cases.

    Article  PubMed  Google Scholar 

  17. Postuma RB, Iranzo A, Hogl B, et al. Risk factors for neurodegeneration in idiopathic rapid eye movement sleep behavior disorder: a multicenter study. Ann Neurol. 2015;77:830–9. This is a multicenter study with the largest cohort population, and the first to identify risk factors for neurodegeneration in RBD.

    Article  PubMed  Google Scholar 

  18. McDade EM, Boot BP, Christianson TJ, et al. Subtle gait changes in patients with REM sleep behavior disorder. Mov Disord : Off J Mov Disord Soc. 2013;28:1847–53.

    Article  Google Scholar 

  19. Chen TZ, Xu GJ, Zhou GA, et al. Postural sway in idiopathic rapid eye movement sleep behavior disorder: a potential marker of prodromal Parkinson’s disease. Brain Res. 2014;1559:26–32.

    Article  CAS  PubMed  Google Scholar 

  20. Terzaghi M, Zucchella C, Rustioni V, et al. Cognitive performances and mild cognitive impairment in idiopathic rapid eye movement sleep behavior disorder: results of a longitudinal follow-up study. Sleep. 2013;36:1527–32.

    PubMed  PubMed Central  Google Scholar 

  21. Howell MJ, Schenck CH. Rapid eye movement sleep behavior disorder and neurodegenerative disease. JAMA Neurol. 2015;72:707–12. A peer review of the last decade of publications on RBD and neurodegenerative disease.

    Article  PubMed  Google Scholar 

  22. Frauscher B, Nomura T, Duerr S, et al. Investigation of autonomic function in idiopathic REM sleep behavior disorder. J Neurol. 2012;259:1056–61.

    Article  PubMed  Google Scholar 

  23. Postuma RB, Gagnon JF, Vendette M, et al. REM sleep behaviour disorder in Parkinson’s disease is associated with specific motor features. J Neurol Neurosurg Psychiatry. 2008;79:1117–21.

    Article  CAS  PubMed  Google Scholar 

  24. Postuma RB, Gagnon JF, Montplaisir J. Rapid eye movement sleep behavior disorder as a biomarker for neurodegeneration: the past 10 years. Sleep Med. 2013;14:763–7. A summary of the multiple biomarkers for neurodegeneration in RBD.

    Article  PubMed  Google Scholar 

  25. Boeve BF, Dickson DW, Olson EJ, et al. Insights into REM sleep behavior disorder pathophysiology in brainstem-predominant Lewy body disease. Sleep Med. 2007;8:60–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Uchiyama M, Isse K, Tanaka K, et al. Incidental Lewy body disease in a patient with REM sleep behavior disorder. Neurology. 1995;45:709–12.

    Article  CAS  PubMed  Google Scholar 

  27. Postuma RB, Gagnon JF, Vendette M, et al. Olfaction and color vision identify impending neurodegeneration in rapid eye movement sleep behavior disorder. Ann Neurol. 2011;69:811–8.

    Article  PubMed  Google Scholar 

  28. Postuma RB, Gagnon JF, Bertrand JA, et al. Parkinson risk in idiopathic REM sleep behavior disorder: preparing for neuroprotective trials. Neurology. 2015;84:1104–13.

    Article  PubMed  PubMed Central  Google Scholar 

  29. McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB consortium. Neurology. 2005;65:1863–72.

    Article  CAS  PubMed  Google Scholar 

  30. Molano J, Boeve B, Ferman T, et al. Mild cognitive impairment associated with limbic and neocortical Lewy body disease: a clinicopathological study. Brain : J Neurol. 2010;133:540–56.

    Article  Google Scholar 

  31. Mahlknecht P, Iranzo A, Hogl B, et al. Olfactory dysfunction predicts early transition to a Lewy body disease in idiopathic RBD. Neurology. 2015;84:654–8.

    Article  PubMed  Google Scholar 

  32. Mahlknecht P, Seppi K, Frauscher B, et al. Probable RBD and association with neurodegenerative disease markers: a population-based study. Mov Disord : Off J Mov Disord Soc. 2015;30:1417–21.

    Article  CAS  Google Scholar 

  33. Dugger BN, Boeve BF, Murray ME, et al. Rapid eye movement sleep behavior disorder and subtypes in autopsy-confirmed dementia with Lewy bodies. Mov Disord : Off J Mov Disord Soc. 2012;27:72–8.

    Article  Google Scholar 

  34. Gilman S, Wenning GK, Low PA, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008;71:670–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Iranzo A, Santamaria J, Rye DB, et al. Characteristics of idiopathic REM sleep behavior disorder and that associated with MSA and PD. Neurology. 2005;65:247–52.

    Article  CAS  PubMed  Google Scholar 

  36. Berg D, Postuma RB, Adler CH, et al. MDS research criteria for prodromal Parkinson’s disease. Mov Disord : Off J Mov Disord Soc. 2015;30:1600–11.

    Article  Google Scholar 

  37. Anang JB, Gagnon JF, Bertrand JA, et al. Predictors of dementia in Parkinson disease: a prospective cohort study. Neurology. 2014;83:1253–60.

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Schenck CH, Boeve BF. The strong presence of REM sleep behavior disorder in PD: clinical and research implications. Neurology. 2011;77:1030–2.

    Article  PubMed  Google Scholar 

  40. Gagnon JF, Vendette M, Postuma RB, et al. Mild cognitive impairment in rapid eye movement sleep behavior disorder and Parkinson’s disease. Ann Neurol. 2009;66:39–47.

    Article  PubMed  Google Scholar 

  41. Onofrj M, Thomas A, D’Andreamatteo G, et al. Incidence of RBD and hallucination in patients affected by Parkinson’s disease: 8-year follow-up. Neurol Sci : Off J Ital Neurol Soc Ital Soc Clin Neurophysiol. 2002;23 Suppl 2:S91–4.

    Article  Google Scholar 

  42. Cochen De Cock V. Recent data on rapid eye movement sleep behavior disorder in patients with Parkinson disease: analysis of behaviors, movements, and periodic limb movements. Sleep Med. 2013;14:749–53.

    Article  PubMed  Google Scholar 

  43. Unger MM, Belke M, Menzler K, et al. Diffusion tensor imaging in idiopathic REM sleep behavior disorder reveals microstructural changes in the brainstem, substantia nigra, olfactory region, and other brain regions. Sleep. 2010;33:767–73.

    PubMed  PubMed Central  Google Scholar 

  44. Scherfler C, Frauscher B, Schocke M, et al. White and gray matter abnormalities in idiopathic rapid eye movement sleep behavior disorder: a diffusion-tensor imaging and voxel-based morphometry study. Ann Neurol. 2011;69:400–7.

    Article  PubMed  Google Scholar 

  45. Ellmore TM, Hood AJ, Castriotta RJ, et al. Reduced volume of the putamen in REM sleep behavior disorder patients. Parkinsonism Relat Disord. 2010;16:645–9.

    Article  PubMed  Google Scholar 

  46. Salsone M, Cerasa A, Arabia G, et al. Reduced thalamic volume in Parkinson disease with REM sleep behavior disorder: volumetric study. Parkinsonism Relat Disord. 2014;20:1004–8.

    Article  CAS  PubMed  Google Scholar 

  47. Zhang JL, Liu G, Hang W, et al. Olfactory function in patients with idiopathic rapid eye movement sleep behavior disorder. Zhonghua er bi yan hou tou jing wai ke za zhi = Chin J Otorhinolaryngol Head Neck Surg. 2013;48:394–7.

    Google Scholar 

  48. St Louis EK, McCarter SJ, Boeve BF, et al. Lesional REM sleep behavior disorder localizes to the dorsomedial pons. Neurology. 2014;83:1871–3.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Tribl GG, Bor-Seng-Shu E, Trindade MC, et al. Wilson’s disease presenting as rapid eye movement sleep behavior disorder: a possible window to early treatment. Arq Neuropsiquiatr. 2014;72:653–8.

    Article  PubMed  Google Scholar 

  50. Compta Y, Valente T, Saura J, et al. Correlates of cerebrospinal fluid levels of oligomeric- and total-alpha-synuclein in premotor, motor and dementia stages of Parkinson’s disease. J Neurol. 2015;262:294–306.

    Article  CAS  PubMed  Google Scholar 

  51. Murray ME, Ferman TJ, Boeve BF, et al. MRI and pathology of REM sleep behavior disorder in dementia with Lewy bodies. Neurology. 2013;81:1681–9.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Garcia-Lorenzo D, Longo-Dos Santos C, Ewenczyk C, et al. The coeruleus/subcoeruleus complex in rapid eye movement sleep behaviour disorders in Parkinson’s disease. Brain : J Neurol. 2013;136:2120–9.

    Article  Google Scholar 

  53. Ellmore TM, Castriotta RJ, Hendley KL, et al. Altered nigrostriatal and nigrocortical functional connectivity in rapid eye movement sleep behavior disorder. Sleep. 2013;36:1885–92. This study demonstrated changes in neural conectivity in RBD patients similar to other synucleinopathies.

    PubMed  PubMed Central  Google Scholar 

  54. Ellmore T, Castriotta R, Suescun J, Schiess M. Negative functional connectivity between substantia nigra and hippocampus in REM sleep behavior disorder. Sleep Med. 2015;16:S12–3.

    Article  Google Scholar 

  55. Mayer G, Bitterlich M, Kuwert T, et al. Ictal SPECT in patients with rapid eye movement sleep behaviour disorder. Brain : J Neurol. 2015;138:1263–70.

    Article  Google Scholar 

  56. Aurora RN, Zak RS, Maganti RK, et al. Best practice guide for the treatment of REM sleep behavior disorder (RBD). J Clin Sleep Med : JCSM : Off Publ Am Acad Sleep Med. 2010;6:85–95.

    Google Scholar 

  57. McCarter SJ, Boswell CL, St Louis EK, et al. Treatment outcomes in REM sleep behavior disorder. Sleep Med. 2013;14:237–42.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Kashihara K, Nomura T, Maeda T, et al. Beneficial effects of Ramelteon on rapid eye movement sleep behavior disorder associated with Parkinson’s disease—results of a multicenter open trial. Intern Med. 2016;55:231–6. Tokyo, Japan.

    Article  PubMed  Google Scholar 

  59. Devnani P, Fernandes R. Management of REM sleep behavior disorder: an evidence based review. Ann Indian Acad Neurol. 2015;18:1–5.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Schenck CH, Bundlie SR, Mahowald MW. Delayed emergence of a parkinsonian disorder in 38 % of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology. 1996;46:388–93.

    Article  CAS  PubMed  Google Scholar 

  61. Schenck CHBS, Mahowald MW. S REM behavior disorder (RBD): delayed emergence of parkinsonism and/or dementia in 65 % of older men initially diagnosed with idiopathic RBD, and an analysis of the minimum-maximum tonic and/or phasic electromyographic abnormalities found during REM sleep. Sleep. 2003;26:A316.

    Google Scholar 

  62. Iranzo AMJ, Santamaria J, Serradell M, Marti M, Valldeoriola F, Vilaseca I, et al. Sixty four percent of patients with idiopathic rem sleep behavior disorder developed a neurological disorder after a mean clinical follow-up of 7 years. Sleep. 2008;31:A280.

    Google Scholar 

  63. Wing YK, Li SX, Mok V, 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;83:470–2.

    Article  PubMed  Google Scholar 

  64. Iranzo A, Fernandez-Arcos A, Tolosa E, et al. Neurodegenerative disorder risk in idiopathic REM sleep behavior disorder: study in 174 patients. PLoS ONE. 2014;9, e89741.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology and UT MOVE, The University of Texas Medical School at Houston, Houston, TX, USA

    Jessika Suescun & Mya Schiess

  2. Movement Disorders, Department of Neurology, University of Texas Health Science Center at Houston, 6431 Fannin St. MSB 7.044, Houston, TX, 77030, USA

    Jessika Suescun

  3. Department of Psychology and Program in Behavioral and Cognitive Neuroscience, The City College of the City University of New York, NAC 7/120 160 Convent Ave, New York, NY, USA

    Timothy M. Ellmore

Authors
  1. Jessika Suescun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Timothy M. Ellmore
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mya Schiess
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mya Schiess.

Ethics declarations

Conflict of Interest

The authors declare that they have no competing interests.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Neurology of Aging

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Suescun, J., Ellmore, T.M. & Schiess, M. REM Sleep Behavior Disorder: a Prodromal Synucleinopathy. Curr Geri Rep 5, 95–102 (2016). https://doi.org/10.1007/s13670-016-0174-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13670-016-0174-9

Keywords

Search

Navigation