Journal of Neurology

, Volume 258, Issue 7, pp 1254–1260 | Cite as

Diffusion tensor imaging and olfactory identification testing in early-stage Parkinson's disease

  • Tyler M. Rolheiser
  • Heather G. Fulton
  • Kimberley P. Good
  • John D. Fisk
  • J. Roger McKelvey
  • Christophe Scherfler
  • Naeem M. Khan
  • Ronald A. Leslie
  • Harold A. Robertson
Original Communication


Evidence from imaging, clinical studies, and pathology suggests that Parkinson’s disease is preceded by a prodromal stage that predates clinical diagnosis by several years but there is no established method for detecting this stage. Olfactory impairment, which is common in Parkinson’s disease and often predates clinical diagnosis, may be a useful biomarker for early Parkinson’s. Evidence is emerging that diffusion imaging parameters might be altered in olfactory tract and substantia nigra in the early stages of clinical Parkinson’s disease, possibly reflecting pathological changes. However, no study has examined olfaction and diffusion imaging in olfactory tract and substantia nigra in the same group of patients. The present study compared newly diagnosed Parkinson’s disease patients with a matched control group using both olfactory testing and diffusion tensor imaging of the substantia nigra and anterior olfactory structures. Fourteen patients with stage 1–2 Hoehn & Yahr Parkinson’s disease were matched to a control group by age and sex. All subjects then completed the University of Pennsylvania Smell Identification Test, as well as a series of MRI scans designed to examine diffusion characteristics of the olfactory tract and the substantia nigra. Olfactory testing revealed significant impairment in the patient group. Diffusion tensor imaging revealed significant group differences in both the substantia nigra and anterior olfactory region, with fractional anisotropy of the olfactory region clearly distinguishing the Parkinson’s subjects from controls. This study suggests that there may be value in combining behavioral (olfaction) and MRI testing to identify early Parkinson’s disease. Since loss of olfaction often precedes the motor symptoms in Parkinson’s disease, the important question raised is “will the combination of olfactory testing and MRI (DTI) testing identify pre-motor Parkinson’s disease?”


Parkinson’s disease Diffusion tensor imaging Olfactory testing Substantia nigra 



TR is grateful to the Faculty of Medicine at Dalhousie University (RAL) for the postdoctoral support grant. We are grateful to Carl Helmick and the staff of the MRI suite, IWK Health Sciences Centre for assistance. Supported by the Dalhousie University Department of Psychiatry Research Fund, Canadian Institutes of Health Research and the Parkinson Society Canada.


  1. 1.
    Fearnley JM, Lees AJ (1991) Ageing and Parkinson’s disease: substantia nigra regional selectivity. Brain 114(Pt 5):2283–2301PubMedCrossRefGoogle Scholar
  2. 2.
    Morrish PK, Rakshi JS, Bailey DL, Sawle GV, Brooks DJ (1998) Measuring the rate of progression and estimating the preclinical period of Parkinson’s disease with [18F] dopa PET. J Neurol Neurosurg Psychiatry 64:314–319PubMedCrossRefGoogle Scholar
  3. 3.
    Marek K, Innis R, van Dyck C, Fussell B, Early M, Eberly S, Oakes D, Seibyl J (2001) [123I]beta-CIT SPECT imaging assessment of the rate of Parkinson’s disease progression. Neurology 57:2089–2094PubMedGoogle Scholar
  4. 4.
    Braak H, Bohl JR, Muller CM, Rub U, de Vos RA, Del Tredici K (2006) Stanley Fahn lecture 2005: the staging procedure for the inclusion body pathology associated with sporadic Parkinson’s disease reconsidered. Mov Disord 21:2042–2051PubMedCrossRefGoogle Scholar
  5. 5.
    Doty RL, Bromley SM, Stern MB (1995) Olfactory testing as an aid in the diagnosis of Parkinson’s disease: development of optimal discrimination criteria. Neurodegeneration 4:93–97PubMedCrossRefGoogle Scholar
  6. 6.
    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 Disord 16:41–46PubMedCrossRefGoogle Scholar
  7. 7.
    Doty RL (2009) The olfactory system and its disorders. Semin Neurol 29:74–81PubMedCrossRefGoogle Scholar
  8. 8.
    Haehner A, Boesveldt S, Berendse HW, Mackay-Sim A, Fleischmann J, Silburn PA, Johnston AN, Mellick GD, Herting B, Reichmann H, Hummel T (2009) Prevalence of smell loss in Parkinson’s disease—a multicenter study. Parkinsonism Relat Disord 15:490–494PubMedCrossRefGoogle Scholar
  9. 9.
    Hawkes CH (2008) The prodromal phase of sporadic Parkinson’s disease: does it exist and if so how long is it? Mov Disord 23:1799–1807PubMedCrossRefGoogle Scholar
  10. 10.
    Hawkes CH (2003) Olfaction in neurodegenerative disorders. Mov Disord 18:364–372PubMedCrossRefGoogle Scholar
  11. 11.
    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 50:34–41PubMedCrossRefGoogle Scholar
  12. 12.
    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 56:173–181PubMedCrossRefGoogle Scholar
  13. 13.
    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):396–399PubMedCrossRefGoogle Scholar
  14. 14.
    Scherfler C, Schocke MF, Seppi K, Esterhammer R, Brenneis C, Jaschke W, Wenning GK, Poewe W (2006) Voxel-wise analysis of diffusion weighted imaging reveals disruption of the olfactory tract in Parkinson’s disease. Brain 129:538–542PubMedCrossRefGoogle Scholar
  15. 15.
    Chan L, Rumpel H, Yap K, Lee E, Loo H-V, Ho G-L, Fook-Chong S, Yuen Y, Tan E-K (2007) Case control study of diffusion tensor imaging in Parkinson’s disease. J Neurol Neurosurg Psychiatry 78:1383–1386PubMedCrossRefGoogle Scholar
  16. 16.
    Menke RA, Scholz J, Miller KL, Deoni S, Jbabdi S, Matthews PM, Zarei M (2009) MRI characteristics of the substantia nigra in Parkinson’s disease: a combined quantitative T1 and DTI study. Neuroimage 47:435–441PubMedCrossRefGoogle Scholar
  17. 17.
    Vaillancourt DE, Spraker MB, Prodoehl J, Abraham I, Corcos DM, Zhou XJ, Comella CL, Little DM (2009) High-resolution diffusion tensor imaging in the substantia nigra of de novo Parkinson disease. Neurology 72:1378–1384PubMedCrossRefGoogle Scholar
  18. 18.
    Skorpil M, Rolheiser T, Robertson H, Sundin A, Svenningsson P (2010) Diffusion tensor fiber tractography of the olfactory track. Magn Reson Imaging. doi: 10.1016/j.mri.2010.07.004
  19. 19.
    Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinicopathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184PubMedCrossRefGoogle Scholar
  20. 20.
    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(3):489–502PubMedCrossRefGoogle Scholar
  21. 21.
    Doty RL, McKeown DA, Lee WW, Shaman P (1995) A study of the test-retest reliability of ten olfactory tests. Chem Senses 20:645–656PubMedCrossRefGoogle Scholar
  22. 22.
    Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE, Watkins KE, Ciccarelli O, Cader MZ, Matthews PM, Behrens TEJ (2006) Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. NeuroImage 31:1487–1505PubMedCrossRefGoogle Scholar
  23. 23.
    Andersson JLR, Jenkinson M, Smith S Non-linear optimization. In: FMRIB technical report TR07JA1 Accessed 18 May 18 2010
  24. 24.
    Andersson JLR, Jenkinson M, Smith S Non-linear registration, aka Spatial normalization. In: FMRIB technical report TR07JA2 Accessed 18 May 2010
  25. 25.
    Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17:427–442PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Tyler M. Rolheiser
    • 1
  • Heather G. Fulton
    • 2
  • Kimberley P. Good
    • 3
  • John D. Fisk
    • 3
  • J. Roger McKelvey
    • 5
  • Christophe Scherfler
    • 7
  • Naeem M. Khan
    • 6
  • Ronald A. Leslie
    • 4
  • Harold A. Robertson
    • 1
    • 8
  1. 1.Department of PharmacologyDalhousie UniversityHalifaxCanada
  2. 2.Department of PsychologyDalhousie UniversityHalifaxCanada
  3. 3.Department of PsychiatryDalhousie UniversityHalifaxCanada
  4. 4.Department of Anatomy and NeurobiologyDalhousie UniversityHalifaxCanada
  5. 5.Department of Medicine/NeurologyDalhousie UniversityHalifaxCanada
  6. 6.Department of Diagnostic ImagingDalhousie UniversityHalifaxCanada
  7. 7.Department of NeurologyInnsbruck Medical UniversityInnsbruckAustria
  8. 8.Brain Repair Centre and Department of Pharmacology, Faculty of MedicineDalhousie UniversityHalifaxCanada

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