Skip to main content

Advertisement

SpringerLink
Log in

Prevalence and timeline of nonmotor symptoms in idiopathic rapid eye movement sleep behavior disorder

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Parkinson disease (PD) patients may experience nonmotor symptoms (NMS) before Parkinsonism onset. Patients with idiopathic REM sleep behavior disorder (IRBD) eventually develop PD and may represent premotor PD. We aimed to evaluate the prevalence and perceived timeline of NMS in IRBD through validated scales and questionnaires used in PD research. In 44 IRBD patients and 40 matched controls, overall NMS evaluation was assessed by NMS questionnaire for Parkinson disease, olfaction by University of Pennsylvania Smell Identification Test, dysautonomia by scales for outcomes in Parkinson’s disease-autonomic, constipation by Rome III criteria, depression by Hospital Anxiety and Depression Scale, cognitive impairment by Montreal cognitive assessment (MoCA) and hypersomnia by Epworth Sleepiness Scale. Patients were asked to report the perceived time of onset of hyposmia, constipation, and depression. Hyposmia (52.3 vs. 20.0 %, p = 0.002) and constipation (56.8 vs. 20.0 %, p = 0.001) were more frequent in patients than in controls. Patients reported more memory problems and showed a trend toward lower score in MoCA. Depression and hypersomnia were not more frequent in patients. The first symptom perceived was RBD in 38.6 % patients, hyposmia in 15.9 %, constipation in 11.4 %, and depression in 6.8 %. The temporal course of the NMS studied was heterogeneous. The three most common presentations were RBD followed by hyposmia; hyposmia followed by RBD; and hyposmia followed by RBD and constipation occurring at the same time span. IRBD patients frequently exhibit NMS that occur in premotor PD, particularly hyposmia and constipation. In IRBD, the perceived timeline of NMS is highly variable. This variability may suggest that pathological changes occurring in IRBD subjects are also heterogeneous and not restricted to the structures that regulate REM sleep.

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Tolosa E, Wenning G, Poewe W (2006) The diagnosis of Parkinson’s disease. Lancet Neurol 5:75–86

    Article  PubMed  Google Scholar 

  2. Spillantini MG, Goedert M (2000) The alpha-synucleinopathies: Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Ann N Y Acad Sci 920:16–27

    Article  CAS  PubMed  Google Scholar 

  3. Fearnley JM, Lees AJ (1991) Ageing and Parkinson’s disease: substantia nigra regional selectivity. Brain 114:2283–2301

    Article  PubMed  Google Scholar 

  4. Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinic-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Chaudhuri KR, Healy DG, Schapira AH (2006) Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol 5:235–245

    Article  PubMed  Google Scholar 

  6. Barone P, Antonini A, Colosimo C et al (2009) The PRIAMO study: a multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson’s disease. Mov Disord 24:1641–1649

    Article  PubMed  Google Scholar 

  7. Mollenhauer B, Trautmann E, Sixel-Döring F et al (2013) Nonmotor and diagnostic findings in subjects with de novo Parkinson disease of the DeNoPa cohort. Neurology 81:1226–1234

    Article  PubMed  Google Scholar 

  8. Müller B, Larsen JP, Wentzel-Larsen T, Skeie GO, Tysnes OB, Parkwest Study Group (2011) Autonomic and sensory symptoms and signs in incident, untreated Parkinson’s disease: frequent but mild. Mov Disord 26:65–72

    Article  PubMed  Google Scholar 

  9. Pont-Sunyer C, Hotter A, Gaig C et al (2014) The onset of nonmotor symptoms in Parkinson’s disease (The ONSET PD Study). Mov Disord. doi:10.1002/mds.26077

    PubMed  Google Scholar 

  10. Tolosa E, Gaig C, Santamaría J, Compta Y (2009) Diagnosis and the premotor phase of Parkinson disease. Neurology 72(Suppl 2):S12–S20

    Article  PubMed  Google Scholar 

  11. Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211

    Article  PubMed  Google Scholar 

  12. Boeve BF (2010) 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 1184:15–54

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Arnulf I (2012) REM sleep behaviour disorder: motor manifestations and pathophysiology. Mov Disord 27:677–689

    Article  PubMed  Google Scholar 

  14. Schenck C, Boeve B, Mahowald M (2013) Delayed emergence of a parkinsonian disorder or dementia in 81 % of older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder: a 16-year update on a previously reported series. Sleep Med 14:744–748

    Article  PubMed  Google Scholar 

  15. Iranzo A, Tolosa E, Gelpi E, Molinuevo JL, Valldeoriola F, Serradell M et al (2013) Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behavior disorder: an observational cohort study. Lancet Neurol 12:443–453

    Article  PubMed  Google Scholar 

  16. Postuma RB, Gagnon JF, Montplaisir J (2013) Rapid eye movement sleep behavior disorder as a biomarker for neurodegeneration: the past 10 years. Sleep Med 14:763–767

    Article  PubMed  Google Scholar 

  17. American Academy of Sleep Medicine (2014) International classification of sleep disorders, 3rd edn. American Academy of Sleep Medicine, Darien

    Google Scholar 

  18. Chaudhuri KR, Martinez-Martin P, Schapira AH, Stocchi F, Sethi K, Odin P et al (2006) International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson’s disease: the NMSQuest Study. Mov Disord 21:916–923

    Article  PubMed  Google Scholar 

  19. Martinez-Martin P, Schapira AHV, Stocchi F, Sethi K, Odin P, MacPhee G et al (2007) Prevalence of nonmotor symptoms in Parkinson’s disease in an international setting; study using nonmotor symptoms questionnaire in 545 patients. Mov Disord 22:1623–1629

    Article  PubMed  Google Scholar 

  20. Doty RL (1995) The smell identification TestTM administration manual, 3rd edn. Sensonics Inc, Philadephia

    Google Scholar 

  21. Visser M, Marinus J, Stiggelbout AM, Van Hilten JJ (2004) Assessment of autonomic dysfunction in Parkinson’s disease: the SCOPA-AUT. Mov Disord 19:1306–1312

    Article  PubMed  Google Scholar 

  22. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC (2006) Functional bowel disorders. Gastroenterology 130:1480–1491

    Article  PubMed  Google Scholar 

  23. Zigmond AS, Snaith RP (1983) The Hospital anxiety and depression scale. Acta Psychiatr Scand 67:361–370

    Article  CAS  PubMed  Google Scholar 

  24. Bjelland I, Dahl AA, Haug TT, Neckelmann D (2002) The validity of the Hospital Anxiety and Depression Scale. An updated literature review. J Psychosom Res 52:69–77

    Article  PubMed  Google Scholar 

  25. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571

    Article  CAS  PubMed  Google Scholar 

  26. Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I et al (2005) The Montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53:695–699

    Article  PubMed  Google Scholar 

  27. Johns MW (1991) A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 14:540–545

    CAS  PubMed  Google Scholar 

  28. Chiba Y, Fujishiro H, Iseki E et al (2012) Retrospective survey of prodromal symptoms in dementia with Lewy bodies: comparison with Alzheimer’s disease. Dement Geriatr Cogn Disord 33:273–281

    Article  PubMed  Google Scholar 

  29. Fujishiro H, Iseki E, Nakamura S et al (2013) Dementia with Lewy bodies: early diagnostic challenges. Psychogeriatrics 13:128–138

    Article  PubMed  Google Scholar 

  30. Ferman TJ, Smith GE, Kantarci K et al (2013) Nonamnestic mild cognitive impairment progresses to dementia with Lewy bodies. Neurology 81:2032–2038

    Article  PubMed Central  PubMed  Google Scholar 

  31. Donaghy PC, O’Brien JT, Thomas AJ (2014) Prodromal dementia with Lewy bodies. Psychol Med 3:1–10

    Google Scholar 

  32. Kim HJ, Park SY, Cho YJ et al (2009) Nonmotor symptoms in de novo Parkinson disease before and after dopaminergic treatment. J Neurol Sci 287:200–204

    Article  CAS  PubMed  Google Scholar 

  33. Gaenslen A, Swid I, Liepelt-Scarfone I, Godau J, Berg D (2011) The patients’ perception of prodromal symptoms before the initial diagnosis of Parkinson’s disease. Mov Disord 26:653–658

    Article  PubMed Central  PubMed  Google Scholar 

  34. Khoo TK, Yarnall AJ, Duncan GW et al (2013) The spectrum of nonmotor symptoms in early Parkinson disease. Neurology 80:276–281

    Article  PubMed Central  PubMed  Google Scholar 

  35. Erro R, Santangelo G, Picillo M et al (2013) Non-motor symptoms in early Parkinson’s disease: a 2-year follow-up study on previously untreated patients. Parkinsonism Relat Disord 19:256–259

    Article  PubMed  Google Scholar 

  36. Stiasny-Kolster K, Doerr Y et al (2005) Combination of ‘idiopathic’ REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT. Brain 128:126–137

    Article  CAS  PubMed  Google Scholar 

  37. Fantini ML, Postuma RB, Montplaisir J, Ferini-Strambi L (2006) Olfactory deficit in idiopathic rapid eye movements sleep behavior disorder. Brain Res Bull 70:386–390

    Article  PubMed  Google Scholar 

  38. Postuma RB, Gagnon JF, Vendette M, Desjardins C, Montplaisir J (2011) Olfaction and color vision identify impending neurodegeneration in rapid eye movement sleep behavior disorder. Ann Neurol 69:811–818

    Article  PubMed  Google Scholar 

  39. Mahlknecht P, Iranzo A, Högl B et al (2015) Olfactory dysfunction predicts early transition to a Lewy body disease in idiopathic RBD. Neurology 2015(84):1–5

    Google Scholar 

  40. Doty RL, Deems DA, Stellar S (1988) Olfactory dysfunction in parkinsonism: a general deficit unrelated to neurologic signs, disease stage, or disease duration. Neurology 38:1237–1244

    Article  CAS  PubMed  Google Scholar 

  41. Ponsen MM, Stoffers D, Booji J, van Eck-Smit BLF, Ech Wolters, Berendse HW (2004) Idiopathic hyposmia as a preclinical sign of Parkinson’s disease. Ann Neurol 56:173–181

    Article  PubMed  Google Scholar 

  42. Ross Petrovitch H, Abbot RD et al (2008) Association of olfactory dysfunction with risk for future Parkinson’s disease. Ann Neurol 63:167–173

    Article  PubMed  Google Scholar 

  43. Iranzo A, Serradell M, Vilaseca I et al (2013) Longitudinal assessment of olfactory function in idiopathic REM sleep behavior disorder. Parkinsonism Relat Disord 19:600–604

    Article  PubMed  Google Scholar 

  44. Hoyles K, Sharama JC (2013) Olfactory loss as a supporting feature in the diagnosis of Parkinson disease: a pragmatic approach. J Neurol 260:2951–2958

    Article  PubMed  Google Scholar 

  45. Olichney JM, Murphy C, Hofsteffer CR et al (2005) Anosmia is very common in the Lewy body variant of Alzheimer’s disease. J Neurol Neurosurg Psychiatry 76:1342–1347

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Westervelt HJ, Stern RA, Tremont G (2003) Odor identification deficits in diffuse Lewy body disease. Cogn Behav Neurol 16:93–99

    Article  PubMed  Google Scholar 

  47. Postuma RB, Lang A, Massicotte-Marquez J, Montplaisir J (2006) Potential early markers of Parkinson disease in idiopathic REM sleep behavior disorder. Neurology 66:845–851

    Article  CAS  PubMed  Google Scholar 

  48. Postuma RB, Gagnon JF, Vendette M, Montplaisir JY (2009) Markers of neurodegeneration in idiopathic rapid eye movement sleep behaviour disorder and Parkinson’s disease. Brain 132:3298–3307

    Article  CAS  PubMed  Google Scholar 

  49. Postuma RB, Gagnon JF, Pelletier A, Montplaisir J (2013) Prodromal autonomic symptoms and signs in Parkinson’s disease and dementia with Lewy bodies. Mov Disord 28:597–604

    Article  PubMed  Google Scholar 

  50. Ferini-Strambi L, Oertel W, Dauvilliers Y, Postuma RB, Marelli S, Iranzo A et al (2014) Autonomic symptoms in idiopathic REM behavior disorder: a multicentre case-control study. J Neurol 261:1112–1118

    Article  PubMed  Google Scholar 

  51. Abbott RD, Petrovitch H, White LR, Masaki KH, Tanner CM, Curb JD et al (2001) Frequency of bowel movements and the future risk of Parkinson’s disease. Neurology 57:456–462

    Article  CAS  PubMed  Google Scholar 

  52. Olanow CW, Wakeman DR, Kordower JH (2014) Peripheral alpha-synuclein and Parkinson’s disease. Mov Disord 29:963–966

    Article  CAS  PubMed  Google Scholar 

  53. Gelpi E, Navarro-Otano J, Tolosa E (2014) Multiple organ involvement in alpha-synuclein pathology in Lewy body disorders. Mov Disord 29:1010–1018

    Article  PubMed  Google Scholar 

  54. Iranzo A, Gelpi E, Tolosa E (2014) Neuropathology of prodromal Lewy body disease. Mov Disord 29:410–415

    Article  PubMed  Google Scholar 

  55. Frauscher B, Nomura T, Duerr S et al (2012) Investigation of autonomic function in idiopathic REM sleep behavior disorder. J Neurol 259:1056–1061

    Article  PubMed  Google Scholar 

  56. Santamaría J, Tolosa E, Valles A (1986) Parkinson’s disease with depression: a possible subgroup of idiopathic parkinsonism. Neurology 36:1130–1133

    Article  PubMed  Google Scholar 

  57. Shiba M, Bower JH, Maraganore DM et al (2000) Anxiety disorders and depressive disorders preceding Parkinson’s disease: a case control study. Mov Disord 15:669–677

    Article  CAS  PubMed  Google Scholar 

  58. Leentjens AFG, Van den Akker M, Metsemakers JFM, Lousberg R, Verhey FRJ (2003) Higher incidence of depression preceding the onset of Parkinson’s disease: a register study. Mov Disord 18:414–418

    Article  PubMed  Google Scholar 

  59. Ferini-Strambi L, Di Gioia MR, Castronovo V, Oldani A, Zucconi M, Cappa SF (2004) Neuropsychological assessment in idiopathic REM sleep behavior disorder (RBD). Does the idiopathic form of RBD really exist? Neurology 62:41–45

    Article  CAS  PubMed  Google Scholar 

  60. Massicotte-Marquez J, Décary A, Gagnon JF, Vendette M, Mathieu A, Postuma RB, Carrier J, Montplaisir J (2008) Executive dysfunction and memory impairment in idiopathic REM sleep behavior disorder. Neurology 70:1250–1257

    Article  CAS  PubMed  Google Scholar 

  61. Aarsland D, Bronnick K, Larsen JP, Tusnes OB, Alves D, for the Norwegian Park West Study Group (2009) Cognitive impairment in incident, untreated Parkinson disease The Norwegian Park West Study. Neurology 72:1121–1126

    Article  CAS  PubMed  Google Scholar 

  62. Yarnall AJ, Breen DP, Duncan DP et al (2014) Characterizing mild cognitive impairment in incident Parkinson disease. The ICICLE study. Neurology 82:308–316

    Article  PubMed  Google Scholar 

  63. Abbott RD, Ross GW, White LR et al (2005) Excessive daytime sleepiness and subsequent development of Parkinson disease. Neurology 65:1442–1446

    Article  CAS  PubMed  Google Scholar 

  64. Gao J, Huang X, Park Y et al (2011) Daytime napping, nighttime sleeping, and Parkinson disease. Am J Epidemiol 173:1032–1038

    Article  PubMed Central  PubMed  Google Scholar 

  65. Schenck CH, Mahowald MW (2002) REM sleep behavior disorder: clinical, developmental, and neuroscience perspectives 16 years after its formal identification in SLEEP. Sleep 2002(25):120–138

    Google Scholar 

  66. Buskova J, Klempir J, Majerova V et al (2011) Sleep disturbances in untreated Parkinson’s disease. J Neurol 258:2254–2259

    Article  PubMed  Google Scholar 

  67. Plomhause L, Dujardin K, Duhamel A et al (2013) Rapid eye movement sleep behavior disorder in treatment-naïve Parkinson disease patients. Sleep Med 14:1035–1037

    Article  PubMed  Google Scholar 

  68. Prudon B, Duncan GW, Khoo TK, Yarnall AJ, Anderson KN (2014) Primary sleep disorder prevalence in patients with newly diagnosed Parkinson’s disease. Mov Disord 29:259–262

    Article  PubMed  Google Scholar 

  69. Iranzo A (2011) Sleep-wake changes in the premotor stage of Parkinson disease. J Neurol Sci 310:283–285

    Article  PubMed  Google Scholar 

  70. Boeve BF (2013) Idiopathic REM sleep behavior disorder in the development of Parkinson’s disease. Lancet Neurol 12:469–482

    Article  PubMed  Google Scholar 

  71. Jellinger KA (2012) Neuropathology of sporadic Parkinson’s disease: evaluation and change of concepts. Mov Disord 27:8–30

    Article  CAS  PubMed  Google Scholar 

  72. Del Tredici K, Braak H (2012) Lewy pathology and neurodegeneration in premotor Parkinson’s disease. Mov Disord 27:597–607

    Article  PubMed  Google Scholar 

Download references

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical standard

The study was approved by the Ethical Committee of Hospital Clínic de Barcelona and was conducted according to the principles of the Declaration of Helsinki. Written informed consent was obtained from all participants.

Author information

Authors and Affiliations

  1. Neurology Service, Hospital Clinic de Barcelona, IDIBAPS, CIBERNED, C/Villarroel 170, 08036, Barcelona, Spain

    Carolina Aguirre-Mardones, Alex Iranzo, Dolores Vilas, Mónica Serradell, Carles Gaig, Joan Santamaría & Eduardo Tolosa

Authors
  1. Carolina Aguirre-Mardones
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alex Iranzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dolores Vilas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mónica Serradell
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Carles Gaig
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joan Santamaría
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Eduardo Tolosa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alex Iranzo.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aguirre-Mardones, C., Iranzo, A., Vilas, D. et al. Prevalence and timeline of nonmotor symptoms in idiopathic rapid eye movement sleep behavior disorder. J Neurol 262, 1568–1578 (2015). https://doi.org/10.1007/s00415-015-7742-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-015-7742-3

Keywords

Search

Navigation