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Olfactory loss as a supporting feature in the diagnosis of Parkinson’s disease: a pragmatic approach

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Abstract

There is ample evidence from a large number of clinical and pathological studies of an early involvement of olfactory bulbs and cortex in the Lewy body pathology in idiopathic Parkinson’s disease (iPD), the olfactory system being one of the first targets of degeneration in this condition. The olfactory dysfunction may be measurably present at the time of initial presentation and progresses in a proportion of patients as the disease advances. Patients with iPD have a more severe olfactory loss as compared to multisystem atrophy whereas the syndromes of corticobasal degeneration and progressive supranuclear palsy have no olfactory loss. A proportion of drug induced parkinsonism may have olfactory loss indicative of primary pathology of dopaminergic degeneration in these patients. Unlike single photon emission tomography, formal measurement of olfaction would provide a supportive role in diagnosing or excluding iPD depending on the duration of an individual patient’s parkinsonian symptoms. Whilst olfaction may be only minimally impaired in early stages and may thus not help to differentiate from other syndromes, an intact olfaction in patients with parkinsonism of few years’ duration would indicate a non-iPD pathology. Olfactory measurement is easy, cheap and now easily available in a number of tests, and olfactory assessment at different stages of parkinsonism should be used as a diagnostic aid for idiopathic PD and would enhance the diagnostic accuracy of iPD when used in conjunction with the UK Parkinson’s disease society Brain Bank supportive criteria for diagnosis of idiopathic Parkinson’s disease.

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References

  1. Gaig C, Tolosa E (2009) When does Parkinson’s disease begin? Mov Disord 24(Suppl 2):S656–S664

    Article  PubMed  Google Scholar 

  2. Politis M, Wu K, Molloy S, GB P, Chaudhuri KR, Piccini P (2010) Parkinson’s disease symptoms: the patient’s perspective. Mov Disord 25(11):1646–1651

    Google Scholar 

  3. Ansari KA, Johnson A (1975) Olfactory function in patients with Parkinson’s disease. J Chronic Dis 28(9):493–497

    Article  PubMed  CAS  Google Scholar 

  4. Murphy C, Schubert CR, Cruickshanks KJ, Klein BE, Klein R, Nondahl DM (2002) Prevalence of olfactory impairment in older adults. JAMA 288(18):2307–2312

    Article  PubMed  Google Scholar 

  5. 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(8):1237–1244

    Article  PubMed  CAS  Google Scholar 

  6. Haehner A, Boesveldt S, Berendse HW, Mackay-Sim A, Fleischmann J, Silburn PA et al (2009) Prevalence of smell loss in Parkinson’s disease–a multicenter study. Parkinsonism Relat Disord 15(7):490–494

    Article  PubMed  CAS  Google Scholar 

  7. Hawkes CH (2008) Parkinson’s disease and aging: same or different process? Mov Disord 23(1):47–53

    Article  PubMed  Google Scholar 

  8. Louis ED, Marder K, Tabert MH, Devanand DP (2008) Mild parkinsonian signs are associated with lower olfactory test score in the community-dwelling elderly. Mov Disord 15:524–530

    Article  Google Scholar 

  9. Sharma JC, Turton J (2012) Olfaction, dyskinesia and profile of weight change in Parkinson’s disease: identifying neurodegenerative phenotypes. Parkinsonism Relat Disord 18:946–970

    Google Scholar 

  10. Berendse HW, Roos DS, Raijmakers P, Doty RL (2011) Motor and non-motor correlates of olfactory dysfunction in Parkinson’s disease. J Neurol Sci 310:21–24

    Article  PubMed  Google Scholar 

  11. Doty RL, Stern MB, Pfeiffer C, Gollomp SM, Hurtig HI (1992) Bilateral olfactory dysfunction in early stage treated and untreated idiopathic Parkinson’s disease. J Neurol Neurosurg Psychiatry 55(2):138–142

    Article  PubMed  CAS  Google Scholar 

  12. Hawkes CH, Shephard BC, Daniel SE (1997) Olfactory dysfunction in Parkinson’s disease. J Neurol Neurosurg Psychiatry 62(5):436–446

    Article  PubMed  CAS  Google Scholar 

  13. Meusel T, Westermann B, Fuhr P, Hummel T, Welge-Lussen A (2010) The course of olfactory deficits in patients with Parkinson’s disease–a study based on psychophysical and electrophysiological measures. Neurosci Lett 486(3):166–170

    Article  PubMed  CAS  Google Scholar 

  14. Herting B, Schulze S, Reichmann H, Haehner A, Hummel T (2008) A longitudinal study of olfactory function in patients with idiopathic Parkinson’s disease. J Neurol 255(3):367–370

    Article  PubMed  Google Scholar 

  15. Morley JF, Duda JE (2010) Olfaction as a biomarker in Parkinson’s disease. Biomark Med 4(5):661–670

    Article  PubMed  CAS  Google Scholar 

  16. Pearce RK, Hawkes CH, Daniel SE (1995) The anterior olfactory nucleus in Parkinson’s disease. Mov Disord 10(3):283–287

    Article  PubMed  CAS  Google Scholar 

  17. Ross GW, Abbott RD, Petrovitch H, Tanner CM, White LR (2012) Pre-motor features of Parkinson’s disease: the Honolulu-Asia aging study experience. Parkinsonism Relat Disord 18(Suppl 1):S199–S202

    Article  PubMed  Google Scholar 

  18. Stern MB, Doty RL, Dotti M, Corcoran P, Crawford D, McKeown DA et al (1994) Olfactory function in Parkinson’s disease subtypes. Neurology 44(2):266–268

    Article  PubMed  CAS  Google Scholar 

  19. Ponsen MM, Stoffers D, Booij J, van Eck-Smit BL, Wolters E, Berendse HW (2004) Idiopathic hyposmia as a preclinical sign of Parkinson’s disease. Ann Neurol 56(2):173–181

    Article  PubMed  Google Scholar 

  20. Ponsen MM, Stoffers D, Twisk JW, Wolters E, Berendse HW (2009) Hyposmia and executive dysfunction as predictors of future Parkinson’s disease: a prospective study. Mov Disord 24(7):1060–1065

    Article  PubMed  Google Scholar 

  21. Ponsen MM, Stoffers D, Wolters E, Booij J, Berendse HW (2010) Olfactory testing combined with dopamine transporter imaging as a method to detect prodromal Parkinson’s disease. J Neurol Neurosurg Psychiatry 81(4):396–399

    Article  PubMed  Google Scholar 

  22. Sherwood L (2007) Human physiology from cells to systems, 6th edn. Thomson Brooks/Cole, Belmont

    Google Scholar 

  23. Braak H, Del Tredici K, Bratzke H, Hamm-Clement J, Sandmann-Keil D, Rub U (2002) Staging of the intracerebral inclusion body pathology associated with idiopathic Parkinson’s disease (preclinical and clinical stages). J Neurol 249 (Suppl 3): III/1–5

    Google Scholar 

  24. 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(2):197–211

    Article  PubMed  Google Scholar 

  25. Silveira-Moriyama L, Holton JL, Kingsbury A, Ayling H, Petrie A, Sterlacci W et al (2009) Regional differences in the severity of Lewy body pathology across the olfactory cortex. Neurosci Lett 453(2):77–80

    Article  PubMed  CAS  Google Scholar 

  26. Mundinano IC, Caballero MC, Ordonez C, Hernandez M, DiCaudo C, Marcilla I et al (2011) Increased dopaminergic cells and protein aggregates in the olfactory bulb of patients with neurodegenerative disorders. Acta Neuropathol 122(1):61–74

    Article  PubMed  CAS  Google Scholar 

  27. Sharma JC, Butcher C (2012) Asymmetry of Olfactory sulcus depth and relationship with olfaction in Parkinson’s disease. European Federation of Neurological Societies, Stockholm

    Google Scholar 

  28. Witt M, Bormann K, Gudziol V, Pehlke K, Barth K, Minovi A et al (2009) Biopsies of olfactory epithelium in patients with Parkinson’s disease. Mov Disord 24(6):906–914

    Article  PubMed  Google Scholar 

  29. Wang J, You H, Liu JF, Ni DF, Zhang ZX, Guan J (2011) Association of olfactory bulb volume and olfactory sulcus depth with olfactory function in patients with Parkinson disease. AJNR Am J Neuroradiol 32(4):677–681

    Article  PubMed  CAS  Google Scholar 

  30. Wattendorf E, Welge-Lussen A, Fiedler K, Bilecen D, Wolfensberger M, Fuhr P et al (2009) Olfactory impairment predicts brain atrophy in Parkinson’s disease. J Neurosci 29(49):15410–15413

    Article  PubMed  CAS  Google Scholar 

  31. Muller A, Reichmann H, Livermore A, Hummel T (2002) 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 Trans 109(5–6):805–811

    CAS  Google Scholar 

  32. Roth J, Radil T, Ruzicka E, Jech R, Tichy J (1998) Apomorphine does not influence olfactory thresholds in Parkinson’s disease. Funct Neurol 13(2):99–103

    PubMed  CAS  Google Scholar 

  33. Bohnen NI, Muller ML, Kotagal V, Koeppe RA, Kilbourn MA, Albin RL et al (2010) Olfactory dysfunction, central cholinergic integrity and cognitive impairment in Parkinson’s disease. Brain 133(Pt 6):1747–1754

    Article  PubMed  Google Scholar 

  34. Wilson RS, Yu L, Schneider JA, Arnold SE, Buchman AS, Bennett DA (2011) Lewy bodies and olfactory dysfunction in old age. Chem Senses 36(4):367–373

    Article  PubMed  Google Scholar 

  35. Hawkes CH, Del Tredici K, Braak H (2009) Parkinson’s disease: the dual hit theory revisited. Ann N Y Acad Sci 1170:615–622

    Article  PubMed  Google Scholar 

  36. Doty RL, Shaman P, Kimmelman CP, Dann MS (1984) University of Pennsylvania Smell identification test: a rapid quantitative olfactory function test for the clinic. Laryngoscope 94(2 Pt 1):176–178

    Article  PubMed  CAS  Google Scholar 

  37. Hummel T, Sekinger B, Wolf SR, Pauli E, Kobal G (1997) ‘Sniffin’ sticks’: olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chem Senses 22(1):39–52

    Article  PubMed  CAS  Google Scholar 

  38. Daum RF, Sekinger B, Kobal G, Lang CJ (2000) Olfactory testing with “sniffin’ sticks” for clinical diagnosis of Parkinson disease. Nervenarzt 71(8):643–650

    Article  PubMed  CAS  Google Scholar 

  39. Welge-Lussen A, Wattendorf E, Schwerdtfeger U, Fuhr P, Bilecen D, Hummel T et al (2009) Olfactory-induced brain activity in Parkinson’s disease relates to the expression of event-related potentials: a functional magnetic resonance imaging study. Neuroscience 162(2):537–543

    Article  PubMed  CAS  Google Scholar 

  40. Silveira-Moriyama L, Schwingenschuh P, O’Donnell A, Schneider SA, Mir P, Carrillo F et al (2009) Olfaction in patients with suspected parkinsonism and scans without evidence of dopaminergic deficit (SWEDDs). J Neurol Neurosurg Psychiatry 80(7):744–748

    Article  PubMed  CAS  Google Scholar 

  41. Stiasny-Kolster K, Doerr Y, Moller JC, Hoffken H, Behr TM, Oertel WH 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(Pt 1):126–137

    PubMed  CAS  Google Scholar 

  42. Rolheiser TM, Fulton HG, Good KP, Fisk JD, McKelvey JR, Scherfler C et al (2011) Diffusion tensor imaging and olfactory identification testing in early-stage Parkinson’s disease. J Neurol 258(7):1254–1260

    Article  PubMed  Google Scholar 

  43. Winkler J, Ehret R, Buttner T, Dillmann U, Fogel W, Sabolek M et al (2011) Parkinson’s disease risk score: moving to a premotor diagnosis. J Neurol 258(Suppl 2):S311–S315

    Article  PubMed  Google Scholar 

  44. Berendse HW, Booij J, Stoffers D, Ponsen MM, Hijman R, Wolters E (2002) Presymptomatic detection of Parkinson’s disease. Tijdschr Gerontol Geriatr 33(2):70–77

    PubMed  CAS  Google Scholar 

  45. Siderowf A, Jennings D, Eberly S, Oakes D, Hawkins KA, Ascherio A, et al (2012) Impaired olfaction and other prodromal features in the Parkinson At-Risk Syndrome study. Mov Disord 27:406–412

    Google Scholar 

  46. Iijima M, Osawa M, Momose M, Kobayakawa T, Saito S, Iwata M et al (2010) Cardiac sympathetic degeneration correlates with olfactory function in Parkinson’s disease. Mov Disord 25(9):1143–1149

    Article  PubMed  Google Scholar 

  47. Oka H, Toyoda C, Yogo M, Mochio S (2010) Olfactory dysfunction and cardiovascular dysautonomia in Parkinson’s disease. J Neurol 257(6):969–976

    Article  PubMed  Google Scholar 

  48. Stephenson R, Houghton D, Sundarararjan S, Doty RL, Stern M, Xie SX et al (2010) Odor identification deficits are associated with increased risk of neuropsychiatric complications in patients with Parkinson’s disease. Mov Disord 25(13):2099–2104

    Article  PubMed  Google Scholar 

  49. Cramer CK, Friedman JH, Amick MM (2010) Olfaction and apathy in Parkinson’s disease. Parkinsonism Relat Disord 16(2):124–126

    Article  PubMed  Google Scholar 

  50. Imamura K, Matumoto S, Mabuchi N, Kobayashi Y, Okayasu N, Watanabe K (2011) Relationship between the regional cerebral blood flow and the cognitive function and anosmia in patients with Parkinson disease and Alzheimer disease. Brain Nerve 61(6):683–690

    Google Scholar 

  51. Baba T, Takeda A, Kikuchi A, Nishio Y, Hosokai Y, Hirayama K et al (2011) Association of olfactory dysfunction and brain. Metabolism in Parkinson’s disease. Mov Disord 26(4):621–628

    Article  PubMed  Google Scholar 

  52. Morley JF, Weintraub D, Mamikonyan E, Moberg PJ, Siderowf AD, Duda JE (2011) Olfactory dysfunction is associated with neuropsychiatric manifestations in Parkinson’s disease. Mov Disord 26(11):2051–2057

    Article  PubMed  Google Scholar 

  53. Deeb J, Shah M, Muhammed N, Gunasekera R, Gannon K, Findley LJ, Hawkes CH (2012) A basic smell test is as sensitive as a dopamine transporter scan: comparison of olfaction, taste and DaTSCAN in the diagnosis of Parkinson’s disease. QJM 103:941–952

    Article  Google Scholar 

  54. Gray AJ, Staples V, Murren K, Dhariwal A, Bentham P (2001) Olfactory identification is impaired in clinic-based patients with vascular dementia and senile dementia of Alzheimer’s type. Int J Geriatr Psychiatry 16:513–517

    Article  PubMed  CAS  Google Scholar 

  55. Olichney JM, Murphy C, Hofstetter CR, Foster K, Hansen LA, Thal LJ, Katzman R (2005) Anosmia id very commom in Lewy body variant of Alzheimer’s disease. J Neurol Neurosurg Psychiatry 76:1342–1347

    Article  PubMed  CAS  Google Scholar 

  56. Liberini P, Parola S, Spano PF, Antonini L (2000) Olfaction in Parkinson’s disease: methods of assessment and clinical relevance. J Neurol 247(2):88–96

    Article  PubMed  CAS  Google Scholar 

  57. Doty RL, Golbe LI, McKeown DA, Stern MB, Lehrach CM, Crawford D (1993) Olfactory testing differentiates between progressive supranuclear palsy and idiopathic Parkinson’s disease. Neurology 43(5):962–965

    Article  PubMed  CAS  Google Scholar 

  58. Muller A, Mungersdorf M, Reichmann H, Strehle G, Hummel T (2002) Olfactory function in Parkinsonian syndromes. J Clin Neurosci 9(5):521–524

    Article  PubMed  CAS  Google Scholar 

  59. Tsuboi Y, Wszolek ZK, Graff-Radford NR, Cookson N, Dickson DW (2003) Tau pathology in the olfactory bulb correlates with Braak stage, Lewy body pathology and apolipoprotein epsilon4. Neuropathol Appl Neurobiol 29(5):503–510

    Article  PubMed  CAS  Google Scholar 

  60. Katzenschlager R, Zijlmans J, Evans A, Watt H, Lees AJ (2004) Olfactory function distinguishes vascular parkinsonism from Parkinson’s disease. J Neurol Neurosurg Psychiatry 75(12):1749–1752

    Article  PubMed  CAS  Google Scholar 

  61. Shah M, Muhammed N, Findley LJ, Hawkes CH (2008) Olfactory tests in the diagnosis of essential tremor. Parkinsonism Relat Disord 14(7):563–568

    Article  PubMed  Google Scholar 

  62. Bovi T, Antonini A, Ottaviani S, Antonioli A, Cecchini MP, Di Francesco V et al (2010) The status of olfactory function and the striatal dopaminergic system in drug-induced parkinsonism. J Neurol 257(11):1882–1889

    Article  PubMed  Google Scholar 

  63. Hensiek A, Bhatia K, Hawkes C (2000) Olfactory function in drug-induced parkinsonism. J Neurol 247(82):303

    Google Scholar 

  64. Doty RL, Singh A, Tetrud J, Langston JW (1992) Lack of major olfactory dysfunction in MPTP-induced parkinsonism. Ann Neurol 32(1):97–100

    Article  PubMed  CAS  Google Scholar 

  65. Iijima M, Kobayakawa T, Saito S, Osawa M, Tsutsumi Y, Hashimoto S et al (2010) Differences in odor identification among clinical subtypes of Parkinson’s disease. Eur J Neurol 18(3):425–429

    Article  Google Scholar 

  66. Suchowersky O et al (2006) Practice patameter: diagnosis and prognosis of new onset Parkinson’s disease (an evidence based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 66:968–975

    Article  PubMed  CAS  Google Scholar 

  67. Wenning GK, Shephard B, Hawkes C, Petruckevitch A, Lees A, Quinn N (1995) Olfactory function in atypical parkinsonian syndromes. Acta Neurol Scand 91(4):247–250

    Article  PubMed  CAS  Google Scholar 

  68. Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55(3):181–184

    Article  PubMed  CAS  Google Scholar 

  69. Varrone A, Marek KL, Jennings D, Innis RB, Seibyl JP (2001) [123I]ß-CIT SPECT imaging demonstrates reduced density of striatal dopamine transporters in Parkinson’s disease and multiple system atrophy. Mov Disord 16:1023–1032

    Article  PubMed  CAS  Google Scholar 

  70. Schreckenberger M, Hägele S, Siessmeier T et al (2004) The dopamine D2 receptor ligand 18F-desmethoxyfallypride: an appropriate fluorinated PET tracer for the differential diagnosis of parkinsonism. Eur J Nucl Med Mol Imaging 31:1128–1135

    Article  PubMed  CAS  Google Scholar 

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  1. Lincoln County Hospital, Lincoln, LN2 5QY, UK

    Katie Hoyles & Jagdish C. Sharma

  2. Nottingham University, Nottingham, UK

    Jagdish C. Sharma

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  1. Katie Hoyles
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Correspondence to Jagdish C. Sharma.

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Hoyles, K., Sharma, J.C. Olfactory loss as a supporting feature in the diagnosis of Parkinson’s disease: a pragmatic approach. J Neurol 260, 2951–2958 (2013). https://doi.org/10.1007/s00415-013-6848-8

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