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Lateralized microstructural changes in early-stage Parkinson’s disease in anterior olfactory structures, but not in substantia nigra

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Abstract

Parkinson’s disease (PD) is a progressive neurological disorder characterized by motor symptoms as well as severe deficits in olfactory function and microstructural changes in olfactory brain regions. Because of the evidence of asymmetric neuropathological features in early-stage PD, we examined whether lateralized microstructural changes occur in olfactory brain regions and the substantia nigra in a group of early-stage PD patients. Using diffusion tensor imaging (DTI) and the University of Pennsylvania Smell Identification Test (UPSIT), we assessed 24 early-stage PD patients (Hoehn and Yahr stage 1 or 2) and 26 healthy controls (HC). We used DTI and a region of interest (ROI) approach to study the microstructure of the left and right anterior olfactory structures (AOS; comprising the olfactory bulbs and anterior end of the olfactory tracts) and the substantia nigra (SN). PD patients had reduced UPSIT scores relative to HC and showed increased mean diffusivity (MD) in the SN, with no lateralized differences. Significant group differences in fractional anisotropy (FA) and MD were seen in the AOS, but these differences were restricted to the right side and were not associated with the primary side of motor symptoms amongst PD patients. No associations were observed between lateralized motor impairment and lateralized microstructural changes in AOS. Impaired olfaction and microstructural changes in AOS are useful for early identification of PD but asymmetries in AOS microstructure seem unrelated to the laterality of PD motor symptoms.

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References

  1. Altinayar S, Oner S, Can S, Kizilay A, Kamisli S, Sarac K (2014) Olfactory dysfunction and its relation olfactory bulb volume in Parkinson’s disease. Eur Rev Med Pharmacol Sci 18(23):3659–3664

    CAS  PubMed  Google Scholar 

  2. Atik A, Stewart T, Zhang Z (2016) Alpha-synuclein as a biomarker for Parkinson’s disease. Brain Pathol 26(3):410–418

    Article  CAS  PubMed  Google Scholar 

  3. Bahar-Fuchs A, Chételat G, Villemagne VL, Moss S, Pike K, Masters CL, Rowe C, Savage G (2010) Olfactory deficits and amyloid-β burden in Alzheimer’s disease, mild cognitive impairment, and healthy aging: a PiB PET study. J Alzheimers Dis 22(4):1081–1087

    Article  PubMed  Google Scholar 

  4. Benedetti B, Charil A, Rovaris M, Judica E, Valsasina P, Sormani MP, Filippi M (2006) Influence of aging on gray and white matter changes assessed by conventional, MT, and DT MRI. Neurology 66(4):535–539

    Article  CAS  PubMed  Google Scholar 

  5. Berg D, Postuma RB, Adler CH, Bloem BR, Chan P, Dubois B, Gasser T, Goetz CG, Halliday G, Joseph L, Lang AE, Liepelt-Scarfone I, Litvan I, Marek K, Obeso J, Oertel W, Olanow CW, Poewe W, Stern M, Deuschl G (2015) MDS research criteria for prodromal Parkinson’s disease. Mov Disord 30(12):1600–1611

    Article  PubMed  Google Scholar 

  6. Berg D, Postuma RB, Bloem B, Chan P, Dubois B, Gasser T, Goetz CG, Halliday GM, Hardy J, Lang AE, Litvan I, Marek K, Obeso J, Oertel W, Olanow CW, Poewe W, Stern M, Deuschi G (2014) Time to redefine PD? Introductory statement of the MDS task force on the definition of Parkinson’s disease. Mov Disord 29(4):454–462

    Article  PubMed  PubMed Central  Google Scholar 

  7. Braak H, Braak E, Bohl J, Reintjes R (1996) Age, neurofibrillary changes, A beta-amyloid and the onset of Alzheimer’s disease. Neurosci Lett 210(2):87–90

    Article  CAS  PubMed  Google Scholar 

  8. 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 21:2042–2051

    Article  PubMed  Google Scholar 

  9. Braak H, Del Tredici K, Rüb 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 

  10. Braak H, Ghebremedhin E, Rüb U, Bratzke H, Del Tredici K (2004) Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 318(1):121–134

    Article  PubMed  Google Scholar 

  11. Brodoehl S, Klingner C, Volk GF, Bitter T, Witte OW, Redecker C (2012) Decreased olfactory bulb volume in idiopathic Parkinson’s disease detected by 3.0-Tesla magnetic resonance imaging. Mov Disord 27(8):1019–1025

    Article  PubMed  Google Scholar 

  12. Brooks DJ, Pavese N (2011) Imaging biomarkers in Parkinson’s disease. Prog Neurobiol 95(4):614–628

    Article  CAS  PubMed  Google Scholar 

  13. Chan LL, Rumpel H, Yap K, Lee E, Loo HV, Ho GL, Fook-Chong S, Yuen Y, Tan EK (2007) Case control study of diffusion tensor imaging in Parkinson’s disease. J Neurol Neurosurg Psychiatry 78(12):1383–1386

    Article  PubMed  PubMed Central  Google Scholar 

  14. Chen S, Tan HY, Wu ZH, Sun CP, He JX, Li XC, Shao M (2014) Imaging of olfactory bulb and gray matter volumes in brain areas associated with olfactory function in patients with Parkinson’s disease and multiple system atrophy. Eur J Radiol 83(3):564–570

    Article  PubMed  Google Scholar 

  15. Del Tredici K, Braak H (2016) Sporadic Parkinson’s disease: development and distribution of α-synuclein pathology. Neuropathol Appl Neurobiol 42(1):33–50

    Article  PubMed  Google Scholar 

  16. Doty RL (2012) Olfaction in Parkinson’s disease and related disorders. Neurobiol Dis 46(3):527–552

    Article  PubMed  Google Scholar 

  17. 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

    Article  CAS  PubMed  Google Scholar 

  18. 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  CAS  PubMed  PubMed Central  Google Scholar 

  19. Djaldetti R, Ziv I, Melamed E (2006) The mystery of motor asymmetry in Parkinson’s disease. Lancet Neurol 5(9):796–802

    Article  PubMed  Google Scholar 

  20. Fahn S, Elton RL (1987) UPDRS program members. Unified Parkinson’s disease rating scale. In: Fahn S, Marsden CD, Goldstein M, Calne DB (eds) Recent developments in Parkinson’s disease, vol 2. Florham Park, Macmillan Healthcare Information, pp 153–163 (293–304)

    Google Scholar 

  21. Gelb DJ, Oliver E, Gilman S (1999) Diagnostic criteria for Parkinson disease. Arch Neurol 56(1):33–39

    Article  CAS  PubMed  Google Scholar 

  22. Good KP, Martzke JS, Milliken HI, Honer WG, Kopala LC (2002) Unirhinal olfactory identification deficits in young male patients with schizophrenia and related disorders: association with impaired memory function. Schizophr Res 56(3):211–223

    Article  PubMed  Google Scholar 

  23. Hakyemez HA, Veyseller B, Ozer F, Ozben S, Bayraktar GI, Gurbuz D, Cetin S, Yildirim YS (2013) Relationship of olfactory function with olfactory bulbus volume, disease duration and Unified Parkinson’s disease rating scale scores in patients with early stage of idiopathic Parkinson’s disease. J Clin Neurosci 20(10):1469–1470

    Article  PubMed  Google Scholar 

  24. Haehner A, Hummel T, Hummel C, Sommer U, Junghanns S, Reichmann H (2007) Olfactory loss may be a first sign of idiopathic Parkinson’s disease. Mov Disord 30 22(6):839–842

    Article  Google Scholar 

  25. Hirata FC, Sato JR, Vieira G, Lucato LT, Leite CC, Bor-Seng-Shu E, Pastorello BF, Otaduy MC, Chaim KT, Campanholo KR, Novaes NP, Melo LM, Gonçalves MR, do Nascimento FB, Teixeira MJ, Barbosa ER, Amaro Jr E, Cardoso EF (2016) Substantia nigra fractional anisotropy is not a diagnostic biomarker of Parkinson’s disease: a diagnostic performance study and meta-analysis. Eur Radiol (epub ahead of print)

  26. Hoehn M, Yahr M (1967) Parkinsonism: onset, progression and mortality. Neurology 17(5):427–442

    Article  CAS  PubMed  Google Scholar 

  27. Kim HJ, Kim SJ, Kim HS, Choi CG, Kim N, Han S, Jang EH, Chung SJ, Lee CS (2013) Alterations of mean diffusivity in brain white matter and deep gray matter in Parkinson’s disease. Neurosci Lett 550:64–68

    Article  CAS  PubMed  Google Scholar 

  28. Kim JY, Lee WY, Chung EJ, Dhong HJ (2007) Analysis of olfactory function and the depth of olfactory sulcus in patients with Parkinson’s disease. Mov Disord 22(11):1563–1566

    Article  PubMed  Google Scholar 

  29. 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 

  30. Kempster PA, Gibb WR, Stern GM, Lees AJ (1989) Asymmetry of substantia nigra neuronal loss in Parkinson’s disease and its relevance to the mechanism of levodopa related motor fluctuations. J Neurol Neurosurg Psychiatry 52(1):72–76

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Klingelhoefer L, Reichmann H (2015) Pathogenesis of Parkinson disease—the gut-brain axis and environmental factors. Nat Rev Neurol 11(11):625–636

    Article  CAS  PubMed  Google Scholar 

  32. Lenfeldt N, Hansson W, Larsson A, Nyberg L, Birgander R, Forsgren L (2013) Diffusion tensor imaging and correlations to Parkinson rating scales. J Neurol 260(11):2823–2830

    Article  PubMed  Google Scholar 

  33. Lenfeldt N, Larsson A, Nyberg L, Birgander R, Forsgren L (2015) Fractional anisotropy in the substantia nigra in Parkinson’s disease: a complex picture. Eur J Neurol 22(10):1408–1414

    Article  CAS  PubMed  Google Scholar 

  34. Li J, Gu C, Zhu L, Zhou Y, Huang H (2016) Changes in olfactory bulb volume in Parkinson’s disease: a systematic review and meta analysis. PLoS One 11(2):e0149286

    Article  PubMed  PubMed Central  Google Scholar 

  35. Metzler-Baddeley C, O’Sullivan MJ, Bells S, Pasternak O, Jones DK (2012) How and how not to correct for CSF-contamination in diffusion MRI. Neuroimage 59(2):1394–1403

    Article  PubMed  Google Scholar 

  36. Mori S, Zhang J (2006) Principles of diffusion tensor imaging and its applications to basic neuroscience research. Neuron 51(5):527–539

    Article  CAS  PubMed  Google Scholar 

  37. Mori F, Tanji K, Zhang H, Kakita A, Takahashi H, Wakabayashi K (2008) Alpha-synuclein pathology in the neostriatum in Parkinson’s disease. Acta Neuropathol 115(4):453–459

    Article  CAS  PubMed  Google Scholar 

  38. Mueller A, Abolmaali ND, Hakimi AR, Gloeckler T, Herting B, Reichmann H, Hummel T (2005) Olfactory bulb volumes in patients with idiopathic Parkinson’s disease a pilot study. J Neural Transm (Vienna) 112(10):1363–1370

    Article  CAS  Google Scholar 

  39. Ofori E, Pasternak O, Planetta PJ, Burciu R, Snyder A, Febo M, Golde TE, Okun MS, Vaillancourt DE (2015) Increased free water in the substantia nigra of Parkinson’s disease: a single-site and multi-site study. Neurobiol Aging 36(2):1097–1104

    Article  CAS  PubMed  Google Scholar 

  40. Olanow CW, Brundin P (2013) Parkinson’s disease and alpha synuclein: is Parkinson’s disease a prion-like disorder? Mov Disord 28(1):31–40

    Article  CAS  PubMed  Google Scholar 

  41. Paschen L, Schmidt N, Wolff S, Cnyrim C, van Eimeren T, Zeuner KE, Deuschl G, Witt K (2015) The olfactory bulb volume in patients with idiopathic Parkinson’s disease. Eur J Neurol 22(7):1068–1073

    Article  CAS  PubMed  Google Scholar 

  42. Péran P, Cherubini A, Assogna F, Piras F, Quattrocchi C, Peppe A, Celsis P, Rascol O, Démonet JF, Stefani A, Pierantozzi M, Pontieri FE, Caltagirone C, Spalletta G, Sabatini U (2010) Magnetic resonance imaging markers of Parkinson’s disease nigrostriatal signature. Brain 133(11):3423–3433

    Article  PubMed  Google Scholar 

  43. Perneger TV (1998) What’s wrong with Bonferroni adjustments. BMJ 316:1236–1238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Planetta PJ, Ofori E, Pasternak O, Burciu RG, Shukla P, DeSimone JC, Okun MS, McFarland NR, Vaillancourt DE (2016) Free-water imaging in Parkinson’s disease and atypical parkinsonism. Brain 139(Pt 2):495–508

    Article  PubMed  Google Scholar 

  45. Postuma RB, Berg D (2016) Advances in markers of prodromal Parkinson disease. Nat Rev Neurol 12(11):622–634

    Article  CAS  PubMed  Google Scholar 

  46. Roalf DR, Turetsky BI, Ozwar K, Balderston CC, Johnson SC, Brensinger CM, Gur RE, Siegel SJ, Moberg PJ (2006) Unirhinal olfactory function in schizophrenia patients and first-degree relatives. J Neuropsychiatr Clin Neurosci 18:389–396

    Article  Google Scholar 

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

    Article  PubMed  Google Scholar 

  48. Rothman KJ (1990) No adjustments are needed for multiple comparisons. Epidemiology 1:43–46

    Article  CAS  PubMed  Google Scholar 

  49. Scherfler C, Esterhammer R, Nocker M, Mahlknecht P, Stockner H, Warwitz B, Spielberger S, Pinter B, Donnemiller E, Decristoforo C, Virgolini I, Schocke M, Poewe W, Seppi K (2013) Correlation of dopaminergic terminal dysfunction and microstructural abnormalities of the basal ganglia and the olfactory tract in Parkinson’s disease. Brain 136(10):3028–3037

    Article  PubMed  Google Scholar 

  50. 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(Pt 2):538–542

    PubMed  Google Scholar 

  51. Schwarz ST, Abaei M, Gontu V, Morgan PS, Bajaj N, Auer DP (2013) Diffusion tensor imaging of nigral degeneration in Parkinson’s disease: a region-of-interest and voxel-based study at 3 T and systematic review of meta-analysis. NeuroImage Clin 3:481–488

    Article  PubMed  PubMed Central  Google Scholar 

  52. Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TEJ, Johansen-Berg H, Bannister PR, De Luca M, Drobnjak I, Flitney DE, Niazy R, Saunders J, Vickers J, Zhang Y, De Stefano N, Brady JM, Matthews PM (2004) Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage 23(S1):208–219

    Article  Google Scholar 

  53. 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(16):1378–1384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Valle-Leija P, Drucker-Colín R (2014) Unilateral olfactory deficit in a hemiparkinson’s disease mouse model. NeuroReport 25(12):948–953

    Article  CAS  PubMed  Google Scholar 

  55. Wang J, Yang QX, Sun X, Vesek J, Mosher Z, Vasavada M, Chu J, Kanekar S, Shivkumar V, Venkiteswaran K, Subramanian T (2015) MRI evaluation of asymmetry of nigrostriatal damage in the early stage of early-onset Parkinson’s disease. Parkinsonsim Relat Disord 21:590–596

    Article  Google Scholar 

  56. Zatorre RJ, Jones-Gotman M (1991) Human olfactory discrimination after unilateral frontal or temporal lobectomy. Brain 114:71–84

    Article  PubMed  Google Scholar 

  57. Zucco GM, Rovatti F, Stevenson RJ (2015) Olfactory asymmetric dysfunction in early Parkinson patients affected by unilateral disorder. Front Psychol 6:1020

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Our sincere appreciation is extended to Mr. Carl Helmick. As well, Denise Lewis, Ceire Storey, Dana Song, Rebecca Hastings, and Rose Gan were instrumental in this project. This study was funded by Canadian Institutes of Health Research MOP-112645, Parkinson Society Canada, Dalhousie Department of Psychiatry Research Fund.

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Authors and Affiliations

  1. Department of Psychiatry, IWK Hospital, Halifax, NS, Canada

    N. Joshi

  2. Department of Psychiatry, Dalhousie University, 4064 AJLB, 5909 Veterans Memorial Lane, Halifax, NS, Canada

    T. M. Rolheiser, B. Rusak, H. A. Robertson & K. P. Good

  3. Department of Psychology, Nova Scotia Health Authority, Central Zone, Halifax, NS, Canada

    J. D. Fisk

  4. Division of Neurology, Department of Medicine, Nova Scotia Health Authority, Halifax, NS, Canada

    J. R. McKelvey, K. Schoffer & H. A. Robertson

  5. Division of Respirology, Department of Medicine, Nova Scotia Health Authority, Halifax, NS, Canada

    G. Phillips

  6. Faculty of Medicine, Dalhousie University, Halifax, NS, Canada

    M. Armstrong

  7. Department of Radiology, IWK Hospital, Halifax, NS, Canada

    M. N. Khan

  8. Department of Medical Neurosciences, Dalhousie University, Halifax, NS, Canada

    R. A. Leslie

  9. Department of Psychology and Neuroscience, Dalhousie University, Halifax, NS, Canada

    B. Rusak & K. P. Good

  10. Department of Pharmacology, Dalhousie University, Halifax, NS, Canada

    H. A. Robertson

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  1. N. Joshi
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  9. R. A. Leslie
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Correspondence to K. P. Good.

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Dr. Harry Robertson is the Director of Clinical Development, Neurodyn Inc.

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Joshi, N., Rolheiser, T.M., Fisk, J.D. et al. Lateralized microstructural changes in early-stage Parkinson’s disease in anterior olfactory structures, but not in substantia nigra. J Neurol 264, 1497–1505 (2017). https://doi.org/10.1007/s00415-017-8555-3

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  • DOI: https://doi.org/10.1007/s00415-017-8555-3

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