Skip to main content

Advertisement

SpringerLink
Log in

Premotor Diagnosis of Parkinson’s Disease

  • Review
  • Published:
Neuroscience Bulletin Aims and scope Submit manuscript

Abstract

Typical Parkinsonian symptoms consist of bradykinesia plus rigidity and/or resting tremor. Some time later postural instability occurs. Pre-motor symptoms such as hyposmia, constipation, REM sleep behavior disorder and depression may antecede these motor symptoms for years. It would be ideal, if we had a biomarker which would allow to predict who with one or two of these pre-motor symptoms will develop the movement disorder Parkinson’s disease (PD). Thus, it is interesting to learn that biopsies of the submandibular gland or colon biopsies may be a means to predict PD, if there is a high amout of abnormally folded alpha-synuclein and phosphorylated alpha-synuclein. This would be of relevance if we would have available means to stop the propagation of abnormal alpha-synuclein which is otherwise one of the reasons of this spreading disease PD.

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

  1. Jellinger K A. Formation and development of Lewy pathology: a critical update. J Neurol 2009, 256: 270–279.

    Article  PubMed  Google Scholar 

  2. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 1997, 276: 2045–2047.

    Article  CAS  PubMed  Google Scholar 

  3. West A, Brummel BE, Braun AR, Rhoades E, Sachs JN. Membrane remodeling and mechanics: Experiments and simulations of a-synuclein. Biochim Biophys Acta 2016, 1858: 1594–1609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Jellinger KA. Post mortem studies in Parkinson’s disease-is it possible to detect brain areas for specific symptoms? J Neural Transm 1999, 56: 1–29.

    Article  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  6. Pan-Montojo F, Anichtchik O, Dening Y, Knels L, Pursche S, Jung R, et al. Progression of Parkinson’s disease pathology is reproduced by intragastric administration of rotenone in mice. PLoS One 2010, 5: e8762.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Pan-Montojo F, Schwarz M, Winkler C, Arnhold M, O’Sullivan GA, Pal A, et al. Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice. Sci Rep 2012, 2: 898–904.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Svensson E, Horváth-Puhó E, Thomsen RW, Djurhuus JC, Pedersen L, Borghammer P, et al. Vagotomy and subsequent risk of Parkinson’s disease. Ann Neurol 2015, 78: 522–529.

    Article  PubMed  Google Scholar 

  9. Tysnes OB, Kenborg L, Herlofson K, Steding-Jessen M, Horn A, Olsen JH, et al. Does vagotomy reduce the risk of Parkinson’s disease? Ann Neurol 2015, 78: 1011–1012.

    Article  PubMed  Google Scholar 

  10. Haehner A, Boesveldt S, Berendse HW, Mackay-Sim A, Fleischmann J, Silburn PA, et al. Prevalence of smell loss in Parkinson’s disease-A multicenter study. Parkinsonism Relat Disord 2009, 15: 490–494.

    Article  CAS  PubMed  Google Scholar 

  11. Berg D, Postuma RB, Bloem B, Chan P, Dubois B, Gasser T, et al. Time to redefine PD? Introductory statement of the MDS task force on the definition of Parkinson’s disease. Mov Disord 2014, 29: 454–462.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Ross GW, Petrovitch H, Abbott RD, Tanner CM, Popper J, Masaki K, et al. Association of olfactory dysfunction with risk for future Parkinson’s disease. Ann Neurol 2008, 63: 167–173.

    Article  PubMed  Google Scholar 

  13. Ansari KA, Johnson A. Olfactory function in patients with Parkinson’s disease. J Chronic Dis 1975, 28: 493–497.

    Article  CAS  PubMed  Google Scholar 

  14. Stern MB, Doty RL, Dotti M, Corcoran P, Crawford D, McKeown DA, et al. Olfactory function in Parkinson’s disease subtypes. Neurology 1994, 44: 266–268.

    Article  CAS  PubMed  Google Scholar 

  15. Hawkes CH, Shephard BC, Daniel SE. Olfactory dysfunction in Parkinson’s disease. J Neurol Neurosurg Psych 1997, 62: 436–446.

    Article  CAS  Google Scholar 

  16. Daum RF, Sekinger B, Kobal G, Lang C. Olfactory testing with “sniffin’ sticks” for clinical diagnosis of Parkinson disease. Nervenarzt 2000, 71: 643–650.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  18. Hummel T, Sekinger B, Wolf SR, Pauli E, Kobal G. “Sniffin’ sticks”: olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chem Senses 1997, 22: 39–52.

    Article  CAS  PubMed  Google Scholar 

  19. Hummel T, Kobal G, Gudziol H, Mackay-Sim A. Normative data for the “Sniffin`Sticks” including tests of odor identification, odor discrimination, and olfactory thresholds: an upgrade based on a group of more than 3,000 subjects. Eur Arch Otorhinolaryngol 2007, 264: 237–243.

    Article  CAS  PubMed  Google Scholar 

  20. Loetsch J, Reichmann H, Hummel T. Different odor tests contribute differently to the evaluation of olfactory loss. Chem Senses 2008, 33: 17–21.

    Article  Google Scholar 

  21. Barz S, Hummel T, Pauli E, Majer M, Lang CJ, Kobal G. Chemosensory event-related potentials in response to trigeminal and olfactory stimulation in idiopathic Parkinson’s disease. Neurology 1997, 49: 1424–1431.

    Article  CAS  PubMed  Google Scholar 

  22. Hummel T. Olfactory evoked potentials as a tool to measure progression of Parkinson’s disease. Focus Med 1999, 14: 47–53.

    Google Scholar 

  23. Herting B, Schulze S, Reichmann H, Haehner A, Hummel T. A longitudinal study of olfactory function in patients with idiopathic Parkinson’s disease. J Neurol 2008, 255: 367–370.

    Article  PubMed  Google Scholar 

  24. Huisman E, Uylings HB, Hoogland PV. A 100% increase of dopaminergic cells in the olfactory bulb may explain hyposmia in Parkinson’s disease. Mov Disord 2004, 19: 687–692.

    Article  PubMed  Google Scholar 

  25. Winner B, Geyer M, Couillard-Despres S, Aigner R, Bogdahn U, Aigner L, et al. Striatal deafferentation increases dopaminergic neurogenesis in the adult olfactory bulb. Exp Neurol 2006, 197: 113–121.

    Article  CAS  PubMed  Google Scholar 

  26. Roth J, Radil T, Ruzickas E, Jech R, Tichý J. Apomorphine does not influence olfactory thresholds in Parkinson’s disease. Funct Neurol 1998, 13: 99–103.

    CAS  PubMed  Google Scholar 

  27. Haehner A, Hummel T, Wolz M, Klingelhöfer L, Fauser M, Storch A, et al. Effects of rasagiline on olfactory function in patients with Parkinson’s disease. Mov Disord 2013, 28: 2023–2027.

    Article  CAS  PubMed  Google Scholar 

  28. Haehner A, Habersack A, Wienecke M, Storch A, Reichmann H, Hummel T. Early Parkinson’s disease patients on rasagiline present with better odor discrimination. J Neural Transm 2015, 122: 1541–1546.

    Article  CAS  PubMed  Google Scholar 

  29. Pearce RKB, Hawkes CH, Daniel SE. The anterior olfactory nucleus in Parkinson’s disease. Mov Disord 1995, 10: 283–287.

    Article  CAS  PubMed  Google Scholar 

  30. 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: 121–134.

    Article  PubMed  Google Scholar 

  31. Müller A, Abolmaali N, Hakimi AR, Gloeckler T, Herting B, Reichmann H, et al. Olfactory bulb volumes in patients with idiopathic Parkinson’s disease-a pilot study. J Neural Transm 2005, 112: 1363–1370.

    Article  Google Scholar 

  32. Harding AJ, Stimson E, Henderson JM, Halliday GM. Clinical correlates of selective pathology in the amygdala of patients with Parkinson’s disease. Brain 2002, 125: 2431–2445.

    Article  PubMed  Google Scholar 

  33. Hudry J, Thobois S, Broussolle E, Adeleine P, Royet JP. Evidence for deficiencies in perceptual and semantic olfactory processes in Parkinson’s disease. Chem Senses 2003, 28: 537–543.

    Article  PubMed  Google Scholar 

  34. Hummel T, Jahnke U, Sommer U, Reichmann H, Müller A. Olfactory function in patients with idiopathic Parkinson’s disease: effects of deep brain stimulation in the subthalamic nucleus. J Neural Transm 2005, 112: 669–676.

    Article  CAS  PubMed  Google Scholar 

  35. Wenning GK, Shephard B, Hawkes C, Petruckevitch A, Lees A, Quinn N. Olfactory function in atypical parkinsonian syndromes. Acta Neurol Scand 1995, 91: 247–250.

    Article  CAS  PubMed  Google Scholar 

  36. Müller A, Reichmann H, Livermore A, Hummel T. Olfactory function in idiopathic Parkinson’s disease (IPD): results from cross-sectional studies in IPD patients and long-term follow-up of de-novo IPD patients. J Neural Transm 2002, 109: 805–811.

    Article  PubMed  Google Scholar 

  37. Müller A, Müngersdorf M, Reichmann H, Strehle G, Hummel T. Olfactory function in Parkinsonian syndromes. J Clin Neurosci 2002, 9: 521–524.

    Article  PubMed  Google Scholar 

  38. Ottaviano G, Frasson G, Nardello E, Martini A. Olfaction deterioration in cognitive disorders in the elderly. Aging Clin Exp Res 2016, 28: 37–45.

    Article  PubMed  Google Scholar 

  39. Müller A, Abolmaali N, Hummel T, Reichmann H. Cardinal symptoms of idiopathic Parkinson disease. Akt Neurol 2003, 30: 239–343.

    Article  Google Scholar 

  40. Sommer U, Hummel T, Cormann K, Mueller A, Frasnelli J, Kropp J, et al. Detection of presymptomatic Parkinson’s disease: combination of olfactory tests, transcranial sonography, and 123-I-FP-CIT-SPECT. Mov Disord 2004, 19: 1196–1202.

    Article  PubMed  Google Scholar 

  41. Becker G, Seufert J, Bogdahn U, Reichmann H, Reiners K. Degeneration of substantia nigra in chronic Parkinson’s disease visualized by transcranial color-coded real-time sonography. Neurology 1995, 45: 182–184.

    Article  CAS  PubMed  Google Scholar 

  42. Berg D, Roggendorf W, Schröder U, Klein R, Tatschner T, Benz P, et al. Echogenicity of the substantia nigra: association with increased iron content and marker for susceptibility to nigrostriatal injury. Arch Neurol 2002, 59: 999–1005.

    Article  PubMed  Google Scholar 

  43. Haehner A, Hummel T, Hummel C, Sommer U, Junghanns S, Reichmann H. Olfactory loss may be a first sign of idiopathic Parkinson’s disease. Mov Disord 2007, 22: 839–842.

    Article  PubMed  Google Scholar 

  44. Berendse HW, Booij J, Francot CM, Bergmans PL, Hijman R, Stoof, JC, et al. Subclinical dopaminergic dysfunction in asymptomatic Parkinson’s disease patients’ relatives with decreased sense of smell. Ann Neurol 2001, 50: 34–41.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  48. Chaudhuri KR, Odin P. The challenge of non-motor symptoms in Parkinson’s disease. Prog Brain Res 2010, 184: 325–341.

    Article  PubMed  Google Scholar 

  49. Cersosimo MG, Raina GB, Pecci C, Pellene A, Calandra CR, Gutiérrez C, et al. Gastrointestinal manifestations in Parkinson’s disease: prevalence and occurrence before motor symptoms. J Neurol 2013, 260: 1332–1338.

    Article  CAS  PubMed  Google Scholar 

  50. Braak H, de Vos RA, Bohl J, Del Tredici K. Gastric alpha-synuclein immunoreactive inclusions in Meissner’s and Auerbach’s plexuses in cases staged for Parkinson’s disease-related brain pathology. Neurosci Lett 2006, 396: 67–72.

    Article  CAS  PubMed  Google Scholar 

  51. Wakabayashi K, Takahashi H, Takeda S, Ohama E, Ikuta F. Parkinson’s disease: the presence of Lewy bodies in Auerbach’s and Meissner’s plexuses. Acta Neuropathol 1988, 76: 217–221.

    Article  CAS  PubMed  Google Scholar 

  52. Shannon KM, Keshavarzian A, Mutlu E, Dodiya HB, Daian D, Jaglin JA, et al. Alpha-synuclein in colonic submucosa in early untreated Parkinson’s disease. Mov Disord 2012, 27: 709–715.

    Article  PubMed  Google Scholar 

  53. 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: 716–719.

    Article  PubMed  Google Scholar 

  54. Beach TG, Adler CH, Serrano G, Sue LI, Walker DG, Dugger BN, et al. Prevalence of submandibular gland synucleinopathy in Parkinson’s disease, dementia with Lewy bodies and other Lewy body disorders. J Parkinsons Dis 2016, 6: 153–163.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Pouclet H, Lebouvier T, Coron E, Varannes SB, Rouaud T, Roy M, et al. A comparison between rectal and colonic biopsies to detect Lewy pathology in Parkinson’s disease. Neurobiol Dis 2012, 45: 305–309.

    Article  PubMed  Google Scholar 

  56. Ruffmann C, Parkkinen L. Gut feelings about a-synuclein in gastrointestinal biopsies: Biomarker in the making? Mov Disord 2016, 31: 193–202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Reichmann H. View point: etiology in Parkinson’s disease. Dual hit or spreading intoxication. J Neurol Sci 2011, 310: 9–11.

    Article  PubMed  Google Scholar 

  58. Gatto NM, Cockburn M, Bornstein J, Manthripragada AD, Ritz B. Well-water consumption and Parkinson’s disease in rural California. Environ Health Perspect 2009, 117: 1912–1918.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Langston JW, Langston EB, Irwin I. MPTP-induced parkinsonism in human and non-human primates-clinical and experimental aspects. Acta Neurol Scand Suppl 1984, 100: 49–54.

    CAS  PubMed  Google Scholar 

  60. Scheperjans F, Aho V, Pereira PA, Koskinen K, Paulin L, Pekkonen E, et al. Gut microbiota are related to Parkinson’s disease and clinical phenotype. Mov Disord 2015, 30: 350–358.

    Article  PubMed  Google Scholar 

  61. Derkinderen P, Shannon KM, Brundin P. Gut feelings about smoking and coffee in Parkinson’s disease. Mov Disord 2014, 29: 976–979.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Howell MJ, Schenck CH. Rapid eye movement sleep behavior disorder and neurodegenerative disease. JAMA Neurol 2015, 72: 707–712.

    Article  PubMed  Google Scholar 

  63. Elbaz A. Prodromal symptoms of Parkinson’s disease: Implications for epidemiological studies of disease etiology. Rev Neurol (Paris) 2016, 172: 503–511.

    Article  CAS  Google Scholar 

  64. Iranzo A, Molinuevo JL, Santamaria J, Serradell M, Martí MJ, Valldeoriola F, et al. Rapid-eye-movement sleep behavior disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol 2006, 5: 572–577.

    Article  PubMed  Google Scholar 

  65. Postuma RB. Prodromal Parkinson’s disease-using REM sleep behavior disorder as a window. Parkinsonism Relat Disord 2014, 20: S1–S4.

    Article  PubMed  Google Scholar 

  66. Stiasny-Kolster K, Doerr Y, Möller JC, Höffken H, Behr TM, Oertel WH, et al. Combination of “idiopathic” REM sleep behavior disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT. Brain 2005, 128: 126–137.

    Article  CAS  PubMed  Google Scholar 

  67. Mahlknecht P, Iranzo A, Högl B, Frauscher B, Müller C, Santamaría J, et al. Olfactory dysfunction predicts early transition to a Lewy body disease in idiopathic RBD. Neurology 2015, 84: 654–658.

    Article  PubMed  Google Scholar 

  68. Iranzo A, Stockner H, Serradell M, Seppi K, Valldeoriola F, Frauscher B, et al. Five-year follow-up of substantia nigra echogenicity in idiopathic REM sleep behavior disorder. Mov Disord 2014, 29: 1774–1780.

    Article  PubMed  Google Scholar 

  69. Aquirre-Mardones C, Iranzo A, Vilas D, Serradell M, Gaig C, Santamaría J, et al. Prevalence and timeline of nonmotor symptoms in idiopathic rapid eye movement sleep behavior disorder. J Neurol 2015, 262: 1568–1578.

    Article  Google Scholar 

  70. 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.

  71. Sprenger FS, Stefanova N, Gelpi E, Seppi K, Navarro-Otano J, Offner F, et al. Enteric nervous system a-synuclein immunoreactivity in idiopathic REM sleep behavior disorder. Neurology 2015, 85: 1761–1768.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Schrempf W, Katona I, Dogan I, Felbert VV, Wienecke M, Heller J, et al. Reduced intraepidermal nerve fiber density in patients with REM sleep behavior disorder. Parkinsonism Relat Disord 2016, 29: 10–16.

    Article  PubMed  Google Scholar 

  73. Sixel-Döring F, Zimmermann J, Wegener A, Mollenhauer B, Trenkwalder C. The evolution of REM sleep behavior disorder in early Parkinson disease. Sleep 2016, 39: 1737–1742.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Mollenhauer B, Zimmermann J, Sixel-Döring F, Focke NK, Wicke T, Ebentheuer J, et al. Monitoring of 30 marker candidates in early Parkinson disease as progression markers. Neurology 2016, 87: 168–177.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Kang SH, Lee HM, Seo WK, Kim JH, Koh SB. The combined effect of REM sleep behavior disorder and hyposmia on cognition and motor phenotype in Parkinson’s disease. J Neurol Sci 368: 374–378.

  76. Huang SF, Chen K, Wu JJ, Liu FT, Zhao J, Lin W, et al. Odor identification test in idiopathic REM-behavior disorder and Parkinson’s disease in China. PLoS One 2016, 11: e0160199.

    Article  PubMed  PubMed Central  Google Scholar 

  77. 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: 114–120.

    Article  PubMed  Google Scholar 

  78. Wang Y, Yang Y, Wu H, Lan D, Chen Y, Zhao Z. Effects of rotigotine on REM sleep behavior disorder in Parkinson disease. J Clin Sleep Med 2016, 12:1403–1409.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Arnaldi D, Antelmi E, St. Louis EK, Postuma RB, Arnulf I. Idiopathic REM sleep behavior disorder and neurodegenerative risk: To tell or not to tell to the patient? How to minimize the risk? Sleep Med Rev 2016, pii: S1087-0792(16)30131-9.

  80. Riedel O, Lotsche J, Spottke A, Deuschl G, Förstl H, Henn F, et al. Frequency of dementia, depression, and other neuropsychiatric symptoms in 1,449 outpatients with Parkinson’s disease. J Neurol 2010, 257: 1073–1082.

    Article  PubMed  Google Scholar 

  81. Schuurman AG, Van den Akker M, Ensinck KT, Metsemakers JF, Knottnerus JA, Leentjens AF, et al. Increased risk of Parkinson’s disease after depression: a retrospective cohort study. Neurology 2002, 58: 1501–1504.

    Article  CAS  PubMed  Google Scholar 

  82. Beavan M, McNeill A, Proukakis C, Hughes DA, Mehta A, Schapira AH. Evolution of prodromal clinical markers of Parkinson disease in a GBA mutation-positive cohort. JAMA Neurol 2015, 72: 201–208.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Gaig C, Vilas D, Infante J, Sierra M, García-Gorostiaga I, Buongiorno M, et al. Nonmotor symptoms in LRRK2 G20195 associated Parkinson’s disease. PLoS One 2014, 9: e108982.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Leentjens AF, Van den Akker M, Metsemakers JF, Lousberg R, Verhey FR. Higher incidence of depression preceding the onset of Parkinson’s disease: a register study. Mov Disord 2003, 18: 414–418.

    Article  PubMed  Google Scholar 

  85. Jacob EI, Gatto NM, Thompson A, Bordelon Y, Ritz B. Occurrence of depression and anxiety prior to Parkinson’s disease. Park Relat Disord 2010, 16: 576–581.

    Article  CAS  Google Scholar 

  86. Schrag A, Horsfall L, Walters K, Noyce A, Petersen I. Prediagnostic presentations of Parkinson’s disease in primary care: a case-control study. Lancet Neurol 2015, 14: 57–64.

    Article  PubMed  Google Scholar 

  87. Ehrt U, Bronnick K, Leentjens AF, Larsen JP, Aarsland D. Depressive symptom profile in Parkinson’s disease: a comparison with depression in elderly patients without Parkinson’s disease. Int J Geriatr Psychiatry 2006, 21: 252–258.

    Article  PubMed  Google Scholar 

  88. Brown RG, Landau S, Hindle JV, Playfer J, Samuel M, Wilson KC, et al. Depression and anxiety related subtypes in Parkinson’s disease. J Neurol Neurosurg Psychiatry 2011, 82: 803–809.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Dresden University of Technology, Fetscherstraße 74, 01307, Dresden, Germany

    Heinz Reichmann

Authors
  1. Heinz Reichmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Heinz Reichmann.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Reichmann, H. Premotor Diagnosis of Parkinson’s Disease. Neurosci. Bull. 33, 526–534 (2017). https://doi.org/10.1007/s12264-017-0159-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12264-017-0159-5

Keywords

Search

Navigation