Skip to main content
SpringerLink
Log in

Selective hyposmia and nigrostriatal dopaminergic denervation in Parkinson’s disease

  • ORIGINAL COMMUNICATION
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Olfactory dysfunction is a frequent and early feature of Parkinson’s disease (PD), often preceding the motor symptoms by several years. Assessment of olfactory deficits may be used in the diagnostic assessment of PD. In this study we investigated the relationship between selective deficits in smell identification and nigrostriatal dopaminergic denervation in patients with PD. Twenty-seven PD patients (Hoehn and Yahr stages I-III) and 27 healthy controls matched for gender and age underwent olfactory testing using the 40-odor University of Pennsylvania Smell Identification Test (UPSIT). PD patients underwent 11C-β-CFT dopamine transporter (DAT) positron emission tomography (PET) imaging and clinical motor examination. We found that total UPSIT scores were significantly lower in the PD than in the control subjects (z = 4.7, p < 0.0001). Analysis of the individual smell scores identified 3 odors with an accuracy of >0.75 for the diagnosis of PD. These odors were banana, licorice, and dill pickle. A PD-specific smell identification score (UPSIT-3) was calculated for these 3 odors. Analysis of the patient PET data demonstrated significant correlations between dorsal striatal DAT activity and the UPSIT-3 (RS = 0.53, p = 0.0027) and total UPSIT (RS = 0.44, p = 0.023) scores. UPSIT-3 (RS = 0.43, p = 0.027) but not total UPSIT (RS = 0.20, ns) correlated with nigral DAT activity. We conclude that patients with PD have selective hyposmia. A simplified UPSIT smell identification test consisting of 3 PD-selective odors had more robust correlation with nigral and dorsal striatial dopaminergic activity compared with the full UPSIT scores in patients with PD. Assessment of selective olfactory deficits may be used as a simplified olfactory screening test in the evaluation of subjects with possible 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. Berendse HW, Booij J, Francot CM, Bergmans PL, Hijman R, Stoof JC, Wolters EC (2001) Subclinical dopaminergic dysfunction in asymptomatic Parkinson’s disease patients’ relatives with a decreased sense of smell. Ann Neurol 50: 34–41

    Article  PubMed  CAS  Google Scholar 

  2. Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F (1973) Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci 20: 415–455

    Article  PubMed  CAS  Google Scholar 

  3. 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: 197–211

    Article  PubMed  Google Scholar 

  4. Braak H, Ghebremedhin E, Rub U, Bratzke H, Del Tredici K (2004) Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 318: 121–134

    Article  PubMed  Google Scholar 

  5. Brooks D (1998) The early diagnosis of Parkinson’s disease. Ann Neurol 44(Suppl. 1): S10–S18

    PubMed  CAS  Google Scholar 

  6. Chaudhuri KR, Yates L, Martinez-Martin P (2005) The non-motor symptom complex of Parkinson’s disease: a comprehensive assessment is essential. Curr Neurol Neurosci Rep 5: 275–283

    PubMed  Google Scholar 

  7. Daum RF, Sekinger B, Kobal G, Lang CJG (2000) Riechprüfung mit “sniffin’ sticks” zur klinischen Diagnostic des Morbus Parkinson. Nervenarzt 71: 643–650

    Article  PubMed  CAS  Google Scholar 

  8. Davila NG, Blakemore LJ, Trombley PQ (2003) Dopamine modulates synaptic transmission between rat olfactory bulb neurons in culture. J Neurophysiol 90: 395–404

    Article  PubMed  CAS  Google Scholar 

  9. 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

    PubMed  CAS  Google Scholar 

  10. Doty RL, Shaman P, Dann M (1984) Development of the University of Pennsylvania Smell Identification Test: a standardized microencapsulated test of olfactory function. Physiol Behav 32: 489–502

    Article  PubMed  CAS  Google Scholar 

  11. 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: 176–178

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  13. 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: 138–142

    PubMed  CAS  Google Scholar 

  14. Double KL, Rowe DB, Hayes M, Chan DK, Blackie J, Corbett A, Joffe R, Fung VS, Morris J, Halliday GM (2003) Identifying the pattern of olfactory deficits in Parkinson disease using the brief smell identification test. Arch Neurol 60: 545–549

    Article  PubMed  Google Scholar 

  15. Fahn S, Elton R (1987) Members of the UPDRS development committee. Unified Parkinson’s disease rating scale. In: Fahn S, Marsden C, Calne D, Goldstein M (eds) Recent developments in Parkinson’s disease. Macmillan Healthcare Information, Florham Park, NJ, pp 153–164

    Google Scholar 

  16. Farley IJ, Price KS, Hornykiewicz O (1977) Dopamine in the limbic regions of the human brain: normal and abnormal. Adv Biochem Psychopharmacol 16: 57–64

    PubMed  CAS  Google Scholar 

  17. Gelb DJ, Oliver E, Gilman S (1999) Diagnostic criteria for Parkinson disease. Arch Neurol 56: 33–39

    Article  PubMed  CAS  Google Scholar 

  18. Hack MA, Saghatelyan A, de Chevigny A, Pfeifer A, Ashery-Padan R, Lledo PM, Gotz M (2005) Neuronal fate determinants of adult olfactory bulb neurogenesis. Nat Neurosci 8: 865–867

    PubMed  CAS  Google Scholar 

  19. Hawkes CH, Shephard BC (1993) Selective anosmia in Parkinson’s disease? Lancet 341: 435–436

    Article  PubMed  CAS  Google Scholar 

  20. Henderson JM, Lu Y, Wang S, Cartwright H, Halliday GM (2003) Olfactory deficits and sleep disturbances in Parkinson’s disease: a case-control survey. J Neurol Neurosurg Psychiatry 74: 956–958

    Article  PubMed  CAS  Google Scholar 

  21. Hoehn M, Yahr M (1967) Parkinsonism: onset, progression, and mortality. Neurology 17: 427–442

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  24. Ichise M, Liow JS, Lu JQ, Takano A, Model K, Toyama H, Suhara T, Suzuki K, Innis RB, Carson RE (2003) Linearized reference tissue parametric imaging methods: application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain. J Cereb Blood Flow Metab 23: 1096–1112

    Article  PubMed  Google Scholar 

  25. Katzenschlager R, Lees AJ (2004) Olfaction and Parkinson’s syndromes: its role in differential diagnosis. Curr Opin Neurol 17: 417–423

    Article  PubMed  Google Scholar 

  26. Kish SJ, Shannak K, Hornykiewicz O (1988) Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson’s disease. N Eng J Med 318: 876–880

    Article  CAS  Google Scholar 

  27. Koeppe RA, Holthoff VA, Frey KA, Kilbourn MR, Kuhl DE (1991) Compartmental analysis of [11C]flumazenil kinetics for the estimation of ligand transport rate and receptor distribution using positron emission tomography. J Cereb Blood Flow Metab 11: 735–744

    PubMed  CAS  Google Scholar 

  28. Korten JJ, Meulstee J (1980) Olfactory disturbances in parkinsonism. Clin Neurol Neurosurg 82: 113–118

    Article  PubMed  CAS  Google Scholar 

  29. Lammertsma AA, Hume SP (1996) Simplified reference tissue model for PET receptor studies. Neuroimage 4: 153–158

    Article  PubMed  CAS  Google Scholar 

  30. Lehrner J, Brucke T, Kryspin-Exner I, Asenbaum S, Podreka I (1995) Impaired olfactory function in Parkinson’s disease. Lancet 345: 1054–1055

    Article  PubMed  CAS  Google Scholar 

  31. Mackinnon A (2000) A spreadsheet for the calculation of comprehensive statistics for the assessment of diagnostic tests and inter-rater agreement. Comput Biol Med 30: 127–134

    Article  PubMed  CAS  Google Scholar 

  32. McLean JH, Shipley MT (1988) Postmitotic, postmigrational expression of tyrosine hydroxylase in olfactory bulb dopaminergic neurons. J Neurosci 8: 3658–3669

    PubMed  CAS  Google Scholar 

  33. Montgomery EBJ, Koller WC, LaMantia TJ, Newman MC, Swanson-Hyland E, Kaszniak AW, Lyons K (2000) Early detection of probable idiopathic Parkinson’s disease: I. Development of a diagnostic test battery. Mov Disord 15: 467–473

    Article  PubMed  Google Scholar 

  34. Montgomery EBJ, Lyons K, Koller WC (2000) Early detection of probable idiopathic Parkinson’s disease: II. A prospective application of a diagnostic test battery. Mov Disord 15: 474–478

    Article  PubMed  Google Scholar 

  35. Moore RY, Whone AL, McGowan S, Brooks DJ (2003) Monoamine neuron innervation of the normal human brain: an 18F-DOPA PET study. Brain Res 982: 137–145

    Article  PubMed  CAS  Google Scholar 

  36. Nagren K, Halldin C, Muller L, Swahn CG, Lehikoinen P (1995) Comparison of [11C]methyl triflate and [11C]methyl iodide in the synthesis of PET radioligands such as [11C]beta-CIT and [11C]beta-CFT. Nucl Med Biol 22: 965–979

    Article  PubMed  CAS  Google Scholar 

  37. Nagren K, Muller L, Halldin C, Swahn CG, Lehikoinen P (1995) Improved synthesis of some commonly used PET radioligands by the use of [11C]methyl triflate. Nucl Med Biol 22: 235–239

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  39. Siderowf A, Newberg A, Chou KL, Lloyd M, Colcher A, Hurtig HI, Stern MB, Doty RL, Mozley PD, Wintering N, Duda JE, Weintraub D, Moberg PJ (2005) [99mTc]TRODAT-1 SPECT imaging correlates with odor identification in early Parkinson disease. Neurology 64: 1716–1720

    Article  PubMed  CAS  Google Scholar 

  40. Stern MB (2004) The preclinical detection of Parkinson’s disease: ready for prime time? Ann Neurol 56: 169–171

    Article  PubMed  Google Scholar 

  41. Tissingh G, Berendse HW, Bergmans P, DeWaard R, Drukarch B, Stoof JC, Wolters EC (2001) Loss of olfaction in de novo and treated Parkinson’s disease: possible implications for early diagnosis. Mov Dis 16: 41–46

    Article  CAS  Google Scholar 

  42. Wang J, Eslinger PJ, Smith MB, Yang QX (2005) Functional magnetic resonance imaging study of human olfaction and normal aging. J Gerontol A Biol Sci Med Sci 60: 510–514

    PubMed  Google Scholar 

  43. Weinhard K (1998) Applications of 3D PET. In: Bendriem B, Townsend DW (eds) The theory and practice of 3D PET. Kluwer Academic Publishers, Boston, pp 133–167

    Google Scholar 

  44. Winner B, Geyer M, Couillard-Despres S, Aigner R, Bogdahn U, Aigner L, Kuhn G, Winkler J (2006) Striatal deafferentation increases dopaminergic neurogenesis in the adult olfactory bulb. Exp Neurol 197: 113–121

    Article  PubMed  CAS  Google Scholar 

  45. Wiseman MB, Nichols TE, Woods RP, Sweeney JA, Mintun MA (1995) Stereotaxic techniques comparing foci intensity and location of activation areas in the brain as obtained using positron emission tomography (PET). J Nucl Med 36(suppl): 93p

    Google Scholar 

  46. Wolters EC, Francot C, Bergmans P, Winogrodzka A, Booij J, Berendse HW, Stoof JC (2000) Preclinical (premotor) Parkinson’s disease. J Neurol 247(Suppl2:II): 103–109

    Google Scholar 

  47. Woods RP, Mazziota JC, Cherry SR (1993) MRI-PET registration with automated algorithm. J Comput Assist Tomogr 17: 536–546

    Article  PubMed  CAS  Google Scholar 

  48. Wu Y, Carson RE (2002) Noise reduction in the simplified reference tissue model for neuroreceptor functional imaging. J Cereb Blood Flow Metab 22: 1440–1452

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank our PET technologists for their skillful performance in data acquisition, cyclotron operators and chemists for their production of [11C]-β-CFT, and research assistants Larry Ivanco, Dana Ivanco, and Kurt Schimmel for assistance.

Author information

Authors and Affiliations

  1. Dept. of Neurology, University of Pittsburgh, Pittsburgh, PA, USA

    Nicolaas I. Bohnen MD, PhD, Satyanarayana Gedela MD, MRCP & Robert Y. Moore MD, PhD

  2. Dept. of Radiology, University of Pittsburgh, Pittsburgh, PA, USA

    Nicolaas I. Bohnen MD, PhD & Chester A. Mathis PhD

  3. Dept. of Veterans Affairs Medical Center, Neurology Service, Pittsburgh, PA, USA

    Nicolaas I. Bohnen MD, PhD

  4. Dept. of Radiology, John Hopkins University, Baltimore, MD, USA

    Hiroto Kuwabara MD, PhD

  5. Dept. of Mathematics and Statistics, University of Pittsburgh, Pittsburgh, PA, USA

    Gregory M. Constantine PhD

  6. Geriatric Research Education Center, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA

    Stephanie A. Studenski MD, MPH

Authors
  1. Nicolaas I. Bohnen MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Satyanarayana Gedela MD, MRCP
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hiroto Kuwabara MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gregory M. Constantine PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chester A. Mathis PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Stephanie A. Studenski MD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Robert Y. Moore MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nicolaas I. Bohnen MD, PhD.

Additional information

Study supported by NIH NS-019608.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bohnen, N.I., Gedela, S., Kuwabara, H. et al. Selective hyposmia and nigrostriatal dopaminergic denervation in Parkinson’s disease. J Neurol 254, 84–90 (2007). https://doi.org/10.1007/s00415-006-0284-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-006-0284-y

Keywords

Search

Navigation