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Neurochemical Research

, Volume 40, Issue 3, pp 421–427 | Cite as

Are Sleep Disturbances Preclinical Markers of Parkinson’s Disease?

  • Altair B. dos Santos
  • Kristi A. Kohlmeier
  • George E. BarretoEmail author
Overview

Abstract

Parkinson’s disease (PD) is a neurobehavioral disorder characterized by motor symptoms and signs, and non-motor abnormalities such as olfactory dysfunction, pain, sleep disorders and cognitive impairment. Amongst these alterations, sleep disturbances play an important role in the pathology, but presence of disturbed sleep is not currently considered in diagnosis. However, sleeping problems may precede by many years the classic motor abnormalities of PD and should be clinically evaluated as a potential marker before disease onset. The first disturbance reported with this potential was the disorder REM sleep behaviour and currently several other disturbances have gained importance as potential markers, such as excessive daytime sleepiness, restless legs syndrome and new evidence also points to changes in circadian rhythms. Here we present a brief review of the major evidence indicating that sleep disturbances precede the motor symptoms in PD and neurodegeneration occurs in regions that could underlie these phenomena in order to provide support for the conclusion that disturbances of sleep should be considered as valuable preclinical markers for PD.

Keywords

Parkinson’s disease Sleep disturbances Non-motor signs Preclinical markers 

References

  1. 1.
    Friedman JH, Millman RP (2008) Sleep disturbances and Parkinson’s disease. CNS Spectr 13:12–17PubMedGoogle Scholar
  2. 2.
    Aarsland D, Zaccai J, Brayne C (2005) A systematic review of prevalence studies of dementia in Parkinson’s disease. Mov Disord 20:1255–1263CrossRefPubMedGoogle Scholar
  3. 3.
    Chaudhuri KR, Healy DG, Schapira AH (2006) Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol 5:235–245CrossRefPubMedGoogle Scholar
  4. 4.
    de Lau LM, Giesbergen PC, de Rijk MC, Hofman A, Koudstaal PJ, Breteler MM (2004) Incidence of parkinsonism and Parkinson disease in a general population: the Rotterdam study. Neurology 63:1240–1244CrossRefPubMedGoogle Scholar
  5. 5.
    Driver JA, Logroscino G, Gaziano JM, Kurth T (2009) Incidence and remaining lifetime risk of Parkinson disease in advanced age. Neurology 72:432–438CrossRefPubMedCentralPubMedGoogle Scholar
  6. 6.
    Schenck CH, Bundlie SR, Mahowald MW (1996) Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology 46:388–393CrossRefPubMedGoogle Scholar
  7. 7.
    Chase MH (2013) Motor control during sleep and wakefulness: clarifying controversies and resolving paradoxes. Sleep Med Rev 17:299–312CrossRefPubMedGoogle Scholar
  8. 8.
    Iranzo A, Aparicio J (2009) A lesson from anatomy: focal brain lesions causing REM sleep behavior disorder. Sleep Med 10:9–12CrossRefPubMedGoogle Scholar
  9. 9.
    Schenck CH, Mahowald MW (2002) REM sleep behavior disorder: clinical, developmental, and neuroscience perspectives 16 years after its formal identification in sleep. Sleep 25:120–138PubMedGoogle Scholar
  10. 10.
    Postuma RB, Gagnon JF, Montplaisir JY (2012) REM sleep behavior disorder: from dreams to neurodegeneration. Neurobiol Dis 46:553–558CrossRefPubMedGoogle Scholar
  11. 11.
    Fantini ML, Farini E, Ortelli P, Zucconi M, Manconi M, Cappa S, Ferini-Strambi L (2011) Longitudinal study of cognitive function in idiopathic REM sleep behavior disorder. Sleep 34:619–625PubMedCentralPubMedGoogle Scholar
  12. 12.
    Postuma RB, Gagnon JF, Vendette M, Montplaisir JY (2009) Idiopathic REM sleep behavior disorder in the transition to degenerative disease. Mov Disord 24:2225–2232CrossRefPubMedGoogle Scholar
  13. 13.
    Schenck CH, Bundlie SR, Mahowald MW (2003) 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 and maximum tonic and/or phasic electromyographic abnormalities found during REM sleep. Sleep 26:A316Google Scholar
  14. 14.
    Tippmann-Peikert M, Olson EJ, Boeve BF, Silber MH (2006) Idiopathic REM sleep behavior disorder: a follow-up of 39 patients. Sleep 29:A272Google Scholar
  15. 15.
    Sixel-Doring F, Trautmann E, Mollenhauer B, Trenkwalder C (2014) Rapid eye movement sleep behavioral events: a new marker for neurodegeneration in early Parkinson disease? Sleep 37:431–438PubMedCentralPubMedGoogle Scholar
  16. 16.
    Pal PK, Calne S, Samii A, Fleming JA (1999) A review of normal sleep and its disturbances in Parkinson’s disease. Parkinsonism Relat Disord 5:1–17CrossRefPubMedGoogle Scholar
  17. 17.
    Arnulf I, Leu S, Oudiette D (2008) Abnormal sleep and sleepiness in Parkinson’s disease. Curr Opin Neurol 21:472–477CrossRefPubMedGoogle Scholar
  18. 18.
    Brito dos Santos A, Campos S, Ribeiro S, Morales L, Gonzalez J, Trindade J, Barreto G (2013) Relação entre qualidade do sono e funções cognitivas em pacientes com doença de Parkinson. Univ Sci 18:269–281Google Scholar
  19. 19.
    Menza MA, Rosen RC (1995) Sleep in Parkinson’s disease. The role of depression and anxiety. Psychosomatics 36:262–266CrossRefPubMedGoogle Scholar
  20. 20.
    Trenkwalder C (1998) Sleep dysfunction in Parkinson’s disease. Clin Neurosci 5:107–114PubMedGoogle Scholar
  21. 21.
    Wong JC, Li Y, Schwarzschild MA, Ascherio A, Gao X (2014) Restless legs syndrome: an early clinical feature of Parkinson disease in men. Sleep 37:369–372PubMedCentralPubMedGoogle Scholar
  22. 22.
    Willison LD, Kudo T, Loh DH, Kuljis D, Colwell CS (2013) Circadian dysfunction may be a key component of the non-motor symptoms of Parkinson’s disease: insights from a transgenic mouse model. Exp Neurol 243:57–66CrossRefPubMedCentralPubMedGoogle Scholar
  23. 23.
    Breen DP, Vuono R, Nawarathna U, Fisher K, Shneerson JM, Reddy AB, Barker RA (2014) Sleep and circadian rhythm regulation in early Parkinson disease. JAMA Neurol 71:589–595CrossRefPubMedCentralPubMedGoogle Scholar
  24. 24.
    Kallio M, Haapaniemi T, Turkka J, Suominen K, Tolonen U, Sotaniemi K, Heikkila VP, Myllyla V (2000) Heart rate variability in patients with untreated Parkinson’s disease. Eur J Neurol 7:667–672CrossRefPubMedGoogle Scholar
  25. 25.
    Bray MS, Shaw CA, Moore MW, Garcia RA, Zanquetta MM, Durgan DJ, Jeong WJ, Tsai JY, Bugger H, Zhang D, Rohrwasser A, Rennison JH, Dyck JR, Litwin SE, Hardin PE, Chow CW, Chandler MP, Abel ED, Young ME (2008) Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression. Am J Physiol Heart Circ Physiol 294:H1036–H1047CrossRefPubMedGoogle Scholar
  26. 26.
    Gerstner JR, Yin JC (2010) Circadian rhythms and memory formation. Nat Rev Neurosci 11:577–588CrossRefPubMedGoogle Scholar
  27. 27.
    Videnovic A, Golombek D (2013) Circadian and sleep disorders in Parkinson’s disease. Exp Neurol 243:45–56CrossRefPubMedCentralPubMedGoogle Scholar
  28. 28.
    Videnovic A, Lazar AS, Barker RA, Overeem S (2014) ‘The clocks that time us’-circadian rhythms in neurodegenerative disorders. Nat Rev Neurol. doi: 10.1038/nrneurol.2014.206
  29. 29.
    Postuma RB, Aarsland D, Barone P, Burn DJ, Hawkes CH, Oertel W, Ziemssen T (2012) Identifying prodromal Parkinson’s disease: pre-motor disorders in Parkinson’s disease. Mov Disord 27:617–626CrossRefPubMedGoogle Scholar
  30. 30.
    Pace-Schott EF, Spencer RM (2014) Sleep-dependent memory consolidation in healthy aging and mild cognitive impairment. Curr Top Behav Neurosci. doi: 10.1007/7854_2014_300
  31. 31.
    de la Riva P, Smith K, Xie SX, Weintraub D (2014) Course of psychiatric symptoms and global cognition in early Parkinson disease. Neurology 83:1096–1103CrossRefPubMedGoogle Scholar
  32. 32.
    Abbott RD, Ross GW, White LR, Tanner CM, Masaki KH, Nelson JS, Curb JD, Petrovitch H (2005) Excessive daytime sleepiness and subsequent development of Parkinson disease. Neurology 65:1442–1446CrossRefPubMedGoogle Scholar
  33. 33.
    Verhave PS, Jongsma MJ, Van den Berg RM, Vis JC, Vanwersch RA, Smit AB, Van Someren EJ, Philippens IH (2011) REM sleep behavior disorder in the marmoset MPTP model of early Parkinson disease. Sleep 34:1119–1125PubMedCentralPubMedGoogle Scholar
  34. 34.
    Barraud Q, Lambrecq V, Forni C, McGuire S, Hill M, Bioulac B, Balzamo E, Bezard E, Tison F, Ghorayeb I (2009) Sleep disorders in Parkinson’s disease: the contribution of the MPTP non-human primate model. Exp Neurol 219:574–582CrossRefPubMedGoogle Scholar
  35. 35.
    Almirall H, Pigarev I, de la Calzada MD, Pigareva M, Herrero MT, Sagales T (1999) Nocturnal sleep structure and temperature slope in MPTP treated monkeys. J Neural Transm 106:1125–1134CrossRefPubMedGoogle Scholar
  36. 36.
    Muller ML, Bohnen NI (2013) Cholinergic dysfunction in Parkinson’s disease. Curr Neurol Neurosci Rep 13:377CrossRefPubMedCentralPubMedGoogle Scholar
  37. 37.
    Datta S, Maclean RR (2007) Neurobiological mechanisms for the regulation of mammalian sleep-wake behavior: reinterpretation of historical evidence and inclusion of contemporary cellular and molecular evidence. Neurosci Biobehav Rev 31:775–824CrossRefPubMedCentralPubMedGoogle Scholar
  38. 38.
    Boucetta S, Cisse Y, Mainville L, Morales M, Jones BE (2014) Discharge profiles across the sleep-waking cycle of identified cholinergic, GABAergic, and glutamatergic neurons in the pontomesencephalic tegmentum of the rat. J Neurosci 34:4708–4727CrossRefPubMedCentralPubMedGoogle Scholar
  39. 39.
    Hirsch EC, Graybiel AM, Duyckaerts C, Javoy-Agid F (1987) Neuronal loss in the pedunculopontine tegmental nucleus in Parkinson disease and in progressive supranuclear palsy. Proc Natl Acad Sci USA 84:5976–5980CrossRefPubMedCentralPubMedGoogle Scholar
  40. 40.
    Jellinger K (1988) The pedunculopontine nucleus in Parkinson’s disease, progressive supranuclear palsy and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 51:540–543CrossRefPubMedCentralPubMedGoogle Scholar
  41. 41.
    Zweig RM, Jankel WR, Hedreen JC, Mayeux R, Price DL (1989) The pedunculopontine nucleus in Parkinson’s disease. Ann Neurol 26:41–46CrossRefPubMedGoogle Scholar
  42. 42.
    Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211CrossRefPubMedGoogle Scholar
  43. 43.
    Boeve BF (2013) Idiopathic REM sleep behaviour disorder in the development of Parkinson’s disease. Lancet Neurol 12:469–482CrossRefPubMedGoogle Scholar
  44. 44.
    Burke RE, Dauer WT, Vonsattel JP (2008) A critical evaluation of the Braak staging scheme for Parkinson’s disease. Ann Neurol 64:485–491CrossRefPubMedCentralPubMedGoogle Scholar
  45. 45.
    Arnulf I, Bonnet AM, Damier P, Bejjani BP, Seilhean D, Derenne JP, Agid Y (2000) Hallucinations, REM sleep, and Parkinson’s disease: a medical hypothesis. Neurology 55:281–288CrossRefPubMedGoogle Scholar
  46. 46.
    Boeve BF, Silber MH, Saper CB, Ferman TJ, Dickson DW, Parisi JE, Benarroch EE, Ahlskog JE, Smith GE, Caselli RC, Tippman-Peikert M, Olson EJ, Lin SC, Young T, Wszolek Z, Schenck CH, Mahowald MW, Castillo PR, Del Tredici K, Braak H (2007) Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. Brain 130:2770–2788CrossRefPubMedGoogle Scholar
  47. 47.
    Garcia-Lorenzo D, Longo-Dos Santos C, Ewenczyk C, Leu-Semenescu S, Gallea C, Quattrocchi G, Pita Lobo P, Poupon C, Benali H, Arnulf I, Vidailhet M, Lehericy S (2013) The coeruleus/subcoeruleus complex in rapid eye movement sleep behaviour disorders in Parkinson’s disease. Brain 136:2120–2129CrossRefPubMedCentralPubMedGoogle Scholar
  48. 48.
    Boissard R, Gervasoni D, Schmidt MH, Barbagli B, Fort P, Luppi PH (2002) The rat ponto-medullary network responsible for paradoxical sleep onset and maintenance: a combined microinjection and functional neuroanatomical study. Eur J Neurosci 16:1959–1973CrossRefPubMedGoogle Scholar
  49. 49.
    Lu J, Sherman D, Devor M, Saper CB (2006) A putative flip-flop switch for control of REM sleep. Nature 441:589–594CrossRefPubMedGoogle Scholar
  50. 50.
    Ellmore TM, Castriotta RJ, Hendley KL, Aalbers BM, Furr-Stimming E, Hood AJ, Suescun J, Beurlot MR, Hendley RT, Schiess MC (2013) Altered nigrostriatal and nigrocortical functional connectivity in rapid eye movement sleep behavior disorder. Sleep 36:1885–1892PubMedCentralPubMedGoogle Scholar
  51. 51.
    Thannickal TC, Lai YY, Siegel JM (2007) Hypocretin (orexin) cell loss in Parkinson’s disease. Brain 130:1586–1595CrossRefPubMedGoogle Scholar
  52. 52.
    Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, Richardson JA, Williams SC, Xiong Y, Kisanuki Y, Fitch TE, Nakazato M, Hammer RE, Saper CB, Yanagisawa M (1999) Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98:437–451CrossRefPubMedGoogle Scholar
  53. 53.
    de Lecea L, Sutcliffe JG (1999) The hypocretins/orexins: novel hypothalamic neuropeptides involved in different physiological systems. Cell Mol Life Sci 56:473–480CrossRefPubMedGoogle Scholar
  54. 54.
    Adamantidis A, de Lecea L (2008) Physiological arousal: a role for hypothalamic systems. Cell Mol Life Sci 65:1475–1488CrossRefPubMedGoogle Scholar
  55. 55.
    Fronczek R, Overeem S, Lee SY, Hegeman IM, van Pelt J, van Duinen SG, Lammers GJ, Swaab DF (2007) Hypocretin (orexin) loss in Parkinson’s disease. Brain 130:1577–1585CrossRefPubMedGoogle Scholar
  56. 56.
    Drouot X, Moutereau S, Nguyen JP, Lefaucheur JP, Creange A, Remy P, Goldenberg F, d’Ortho MP (2003) Low levels of ventricular CSF orexin/hypocretin in advanced PD. Neurology 61:540–543CrossRefPubMedGoogle Scholar
  57. 57.
    Burlet S, Tyler CJ, Leonard CS (2002) Direct and indirect excitation of laterodorsal tegmental neurons by hypocretin/orexin peptides: implications for wakefulness and narcolepsy. J Neurosci 22:2862–2872PubMedGoogle Scholar
  58. 58.
    Gao J, Huang X, Park Y, Hollenbeck A, Blair A, Schatzkin A, Chen H (2011) Daytime napping, nighttime sleeping, and Parkinson disease. Am J Epidemiol 173:1032–1038CrossRefPubMedCentralPubMedGoogle Scholar
  59. 59.
    Zoccolella S, Savarese M, Lamberti P, Manni R, Pacchetti C, Logroscino G (2011) Sleep disorders and the natural history of Parkinson’s disease: the contribution of epidemiological studies. Sleep Med Rev 15:41–50CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Altair B. dos Santos
    • 1
  • Kristi A. Kohlmeier
    • 2
  • George E. Barreto
    • 3
    Email author
  1. 1.Department of Biological SciencesUniversidade Estadual do Sudoeste da BahiaVitória Da ConquistaBrazil
  2. 2.Department of Drug Design and Pharmacology, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
  3. 3.Departmento de Nutrición y Bioquímica, Facultad de CienciasPontificia Universidad JaverianaBogotá DCColombia

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