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Table of Contents
Vol. 16, No. 1, 2008
Issue release date: December 2007
Section title: Paper
Neurosignals 2008;16:35–40
(DOI:10.1159/000109757)

Olfactory Dysfunction in Parkinson’s Disease

Kranick S.M.a · Duda J.E.a, b
aDepartment of Neurology, University of Pennsylvania School of Medicine, and bParkinson’s Disease Research, Education and Clinical Center (PADRECC), Philadelphia Veterans Affairs Medical Center, Philadelphia, Pa., USA
email Corresponding Author

Abstract

Prior to the onset of the cardinal motor features of idiopathic Parkinson‘s disease (PD), other manifestations of neurodegeneration such as olfactory dysfunction are often apparent. Characterizing these potential biomarkers of preclinical PD is particularly important in identifying individuals who will go on to develop disabling symptoms, and thus be good candidates for new neuroprotective strategies. As shown by the Braak neuropathologic staging of PD, the olfactory system is among the first neuronal populations to display Lewy body pathology. Clinically, loss of smell can be easily tested in the office using several validated techniques and is often helpful to the physician in distinguishing idiopathic PD from other forms of parkinsonism. Recent findings have indicated that a decline in olfaction may be observed in selected at-risk patients, which has significant implications for identifying potential study populations. Ongoing studies of olfactory dysfunction may also reveal potential for use as a medication-independent biomarker of disease progression in addition to use as a biomarker for the diagnosis of PD.

© 2008 S. Karger AG, Basel


  

Key Words

  • Olfaction
  • Parkinson’s disease
  • Neuropathology
  • Smell
  • Olfactory bulb
  • Parkinsonian disorders
  • Dopaminergic functional imaging

References

  1. Ansari KA, Johnson A: Olfactory function in patients with Parkinson’s disease. J Chronic Dis 1975;28:493–497.
  2. 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.
  3. Double KL, Rowe DB, Hayes M, Chan DK, Blackie J, Corbett A, Joffe R, Fung VS, Morris J, Halliday GM: Identifying the pattern of olfactory deficits in Parkinson disease using the brief smell identification test. Arch Neurol 2003;60:545–549.
  4. Hawkes CH, Shephard BC, Daniel SE: Olfactory dysfunction in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1997;62:436–446.
  5. Mesholam RI, Moberg PJ, Mahr RN, Doty RL: Olfaction in neurodegenerative disease: a meta-analysis of olfactory functioning in Alzheimer’s and Parkinson’s diseases. Arch Neurol 1998;55:84–90.
  6. Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E: Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 2003;24:197–211.
  7. Pearce RK, Hawkes CH, Daniel SE: The anterior olfactory nucleus in Parkinson’s disease. Mov Disord 1995;10:283–287.
  8. Duda JE: Pathology and neurotransmitter abnormalities of dementia with Lewy bodies. Dement Geriatr Cogn Disord 2004;17(suppl 1):3–14.
  9. Del Tredici K, Rub U, De Vos RA, Bohl JR, Braak H: Where does Parkinson disease pathology begin in the brain? J Neuropathol Exp Neurol 2002;61:413–426.
  10. Duda JE, Shah U, Arnold SE, Lee VM, Trojanowski JQ: The expression of α-, β-, and γ-synucleins in olfactory mucosa from patients with and without neurodegenerative diseases. Exp Neurol 1999;160:515–522.
  11. Braak H, Rub U, Gai WP, Del Tredici K: Idiopathic Parkinson’s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm 2003;110:517–536.
  12. Silveira-Moriyama L, Holton J, Kingsbury A, Ayling H. Petrie A, Sterlacci W, Poewe W, Maier H, Lees AJ, Revesz T: The primary olfactory cortex in idiopathic Parkinson’s disease (IPD) and incidental Lewy body disease (ILBD). Mov Disord 2007;22:S91.

    External Resources

  13. Hurtig HI, Trojanowski JQ, Galvin J, Ewbank D, Schmidt ML, Lee VM, Clark CM, Glosser G, Stern MB, Gollomp SM, Arnold SE: α-Synuclein cortical Lewy bodies correlate with dementia in Parkinson’s disease. Neurology 2000;54:1916–1921.
  14. 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.
  15. Doty RL, Stern MB, Pfeiffer C, Gollomp SM, Hurtig HI: Bilateral olfactory dysfunction in early stage treated and untreated idiopathic Parkinson’s disease. J Neurol Neurosurg Psychiatry 1992;55:138–142.
  16. 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.
  17. Hsia AY, Vincent JD, Lledo PM: Dopamine depresses synaptic inputs into the olfactory bulb. J Neurophysiol 1999;82:1082–1085.
  18. Duchamp-Viret P, Coronas V, Delaleu JC, Moyse E, Duchamp A: Dopaminergic modulation of mitral cell activity in the frog olfactory bulb: a combined radioligand binding-electrophysiological study. Neuroscience 1997;79:203–216.
  19. Koller WC, Langston JW, Hubble JP, Irwin I, Zack M, Golbe L, Forno L, Ellenberg J, Kurland L, Ruttenber AJ, et al: Does a long preclinical period occur in Parkinson’s disease? Geriatrics 1991;46(suppl 1):8–15.

    External Resources

  20. Wolters EC, Francot C, Bergmans P, Winogrodzka A, Booij J, Berendse HW, Stoof JC: Preclinical (premotor) Parkinson’s disease. J Neurol 2000;247(suppl 2):II103–II109.
  21. Horstink MW, Morrish PK: Preclinical diagnosis of Parkinson’s disease. Adv Neurol 1999;80:327–333.
  22. Doty RL, Shaman P, Kimmelman CP, Dann MS: University of Pennsylvania Smell Identification Test: a rapid quantitative olfactory function test for the clinic. Laryngoscope 1984;94:176–178.
  23. Bohnen NI, Gedela S, Kuwabara H, Constantine GM, Mathis CA, Studenski SA, Moore RY: Selective hyposmia and nigrostriatal dopaminergic denervation in Parkinson’s disease. J Neurol 2007;254:84–90.
  24. 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.
  25. Potagas C, Dellatolas G, Ziegler M, Leveteau J, Bathien N, Mac Leod P, Rondot P: Clinical assessment of olfactory dysfunction in Parkinson’s disease. Mov Disord 1998;13:394–399.
  26. Tissingh G, Berendse HW, Bergmans P, DeWaard R, Drukarch B, Stoof JC, Wolters EC: Loss of olfaction in de novo and treated Parkinson’s disease: possible implications for early diagnosis. Mov Disord 2001;16:41–46.
  27. Muller 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.
  28. Sobel N, Thomason ME, Stappen I, Tanner CM, Tetrud JW, Bower JM, Sullivan EV, Gabrieli JD: An impairment in sniffing contributes to the olfactory impairment in Parkinson’s disease. Proc Natl Acad Sci USA 2001;98:4154–4159.
  29. Thesen T, Murphy C: Reliability analysis of event-related brain potentials to olfactory stimuli. Psychophysiology 2002;39:733–738.
  30. 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.
  31. Lotsch J, Hummel T: The clinical significance of electrophysiological measures of olfactory function. Behav Brain Res 2006;170:78–83.
  32. Montgomery EB Jr, Lyons K, Koller WC: Early detection of probable idiopathic Parkinson’s disease. II. A prospective application of a diagnostic test battery. Mov Disord 2000;15:474–478.
  33. Lee PH, Yeo SH, Kim HJ, Youm HY: Correlation between cardiac 123I-MIBG and odor identification in patients with Parkinson’s disease and multiple system atrophy. Mov Disord 2006;21:1975–1977.
  34. Braune S, Reinhardt M, Bathmann J, Krause T, Lehmann M, Lucking CH: Impaired cardiac uptake of meta-[123I]iodobenzylguanidine in Parkinson’s disease with autonomic failure. Acta Neurol Scand 1998;97:307–314.
  35. Yoshita M: Differentiation of idiopathic Parkinson’s disease from striatonigral degeneration and progressive supranuclear palsy using iodine-123 meta-iodobenzylguanidine myocardial scintigraphy. J Neurol Sci 1998;155:60–67.
  36. 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: [99mTc]TRODAT-1 SPECT imaging correlates with odor identification in early Parkinson disease. Neurology 2005;64:1716–1720.
  37. Ponsen MM, Stoffers D, Booij J, van Eck-Smit BL, Wolters E, Berendse HW: Idiopathic hyposmia as a preclinical sign of Parkinson’s disease. Ann Neurol 2004;56:173–181.
  38. 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.
  39. Sommer U, Hummel T, Cormann K, Mueller A, Frasnelli J, Kropp J, Reichmann H: Detection of presymptomatic Parkinson’s disease: combining smell tests, transcranial sonography, and SPECT. Mov Disord 2004;19:1196–1202.
  40. 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.
  41. Suchowersky O, Reich S, Perlmutter J, Zesiewicz T, Gronseth G, Weiner WJ: Practice parameter: diagnosis and prognosis of new onset Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006;66:968–975.
  42. McShane RH, Nagy Z, Esiri MM, King E, Joachim C, Sullivan N, Smith AD: Anosmia in dementia is associated with Lewy bodies rather than Alzheimer’s pathology. J Neurol Neurosurg Psychiatry 2001;70:739–743.
  43. Olichney JM, Murphy C, Hofstetter CR, Foster K, Hansen LA, Thal LJ, Katzman R: Anosmia is very common in the Lewy body variant of Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2005;76:1342–1347.
  44. Hawkes C: Olfaction in neurodegenerative disorder. Mov Disord 2003;18:364–372.
  45. Katzenschlager R, Lees AJ: Olfaction and Parkinson’s syndromes: its role in differential diagnosis. Curr Opin Neurol 2004;17:417–423.
  46. Doty RL, Singh A, Tetrud J, Langston JW: Lack of major olfactory dysfunction in MPTP-induced parkinsonism. Ann Neurol 1992;32:97–100.
  47. Khan NL, Katzenschlager R, Watt H, Bhatia KP, Wood NW, Quinn N, Lees AJ: Olfaction differentiates parkin disease from early-onset parkinsonism and Parkinson disease. Neurology 2004;62:1224–1226.
  48. Hensiek AE, Bhatia K, Hawkes CH: Olfactory function in drug induced parkinsonism. J Neurol 2000;247:P303.

    External Resources

  49. Berendse HW, Booij J, Francot CM, Bergmans PL, Hijman R, Stoof JC, Wolters EC: Subclinical dopaminergic dysfunction in asymptomatic Parkinson’s disease patients’ relatives with a decreased sense of smell. Ann Neurol 2001;50:34–41.
  50. Marras C, Goldman S, Smith A, Barney P, Aston D, Comyns K, Korell M, Langston JW, Ross GW, Tanner CM: Smell identification ability in twin pairs discordant for Parkinson’s disease. Mov Disord 2005;20:687–693.
  51. Stern MB, Doty RL, Dotti M, Corcoran P, Crawford D, McKeown DA, Adler C, Gollomp S, Hurtig H: Olfactory function in Parkinson’s disease subtypes. Neurology 1994;44:266–268.
  52. Hummel T: Olfactory evoked potentials as a tool to measure progression of Parkinson’s Disease; in Chase T, Bedard B (eds): Focus on Medicine: New Developments in the Drug Therapy of Parkinson’s Disease. Oxford, Blackwell Science, 1999, vol 14, pp 47–53.
  53. Siderowf A, Stern MB: Preclinical diagnosis of Parkinson’s disease: are we there yet? Curr Neurol Neurosci Rep 2006;6:295–301.

  

Author Contacts

John Duda, MD
Parkinson’s Disease Research, Education and Clinical Center
Mail Stop No. 127, Philadelphia VAMC, 3900 Woodland Avenue
Philadelphia, PA 19104 (USA)
Tel. +1 215 823 5934, Fax +1 215 823 4603, E-Mail john.duda@va.gov

  

Article Information

Published online: December 5, 2007
Number of Print Pages : 6
Number of Figures : 1, Number of Tables : 0, Number of References : 53

  

Publication Details

Neurosignals

Vol. 16, No. 1, Year 2008 (Cover Date: December 2007)

Journal Editor: Ip, N.Y. (Hong Kong)
ISSN: 1424–862X (print), 1424–8638 (Online)

For additional information: http://www.karger.com/NSG


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Prior to the onset of the cardinal motor features of idiopathic Parkinson‘s disease (PD), other manifestations of neurodegeneration such as olfactory dysfunction are often apparent. Characterizing these potential biomarkers of preclinical PD is particularly important in identifying individuals who will go on to develop disabling symptoms, and thus be good candidates for new neuroprotective strategies. As shown by the Braak neuropathologic staging of PD, the olfactory system is among the first neuronal populations to display Lewy body pathology. Clinically, loss of smell can be easily tested in the office using several validated techniques and is often helpful to the physician in distinguishing idiopathic PD from other forms of parkinsonism. Recent findings have indicated that a decline in olfaction may be observed in selected at-risk patients, which has significant implications for identifying potential study populations. Ongoing studies of olfactory dysfunction may also reveal potential for use as a medication-independent biomarker of disease progression in addition to use as a biomarker for the diagnosis of PD.

© 2008 S. Karger AG, Basel


  

Author Contacts

John Duda, MD
Parkinson’s Disease Research, Education and Clinical Center
Mail Stop No. 127, Philadelphia VAMC, 3900 Woodland Avenue
Philadelphia, PA 19104 (USA)
Tel. +1 215 823 5934, Fax +1 215 823 4603, E-Mail john.duda@va.gov

  

Article Information

Published online: December 5, 2007
Number of Print Pages : 6
Number of Figures : 1, Number of Tables : 0, Number of References : 53

  

Publication Details

Neurosignals

Vol. 16, No. 1, Year 2008 (Cover Date: December 2007)

Journal Editor: Ip, N.Y. (Hong Kong)
ISSN: 1424–862X (print), 1424–8638 (Online)

For additional information: http://www.karger.com/NSG


Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: 12/5/2007
Issue release date: December 2007

Number of Print Pages: 6
Number of Figures: 1
Number of Tables: 0

ISSN: 1424-862X (Print)
eISSN: 1424-8638 (Online)

For additional information: http://www.karger.com/NSG


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Ansari KA, Johnson A: Olfactory function in patients with Parkinson’s disease. J Chronic Dis 1975;28:493–497.
  2. 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.
  3. Double KL, Rowe DB, Hayes M, Chan DK, Blackie J, Corbett A, Joffe R, Fung VS, Morris J, Halliday GM: Identifying the pattern of olfactory deficits in Parkinson disease using the brief smell identification test. Arch Neurol 2003;60:545–549.
  4. Hawkes CH, Shephard BC, Daniel SE: Olfactory dysfunction in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1997;62:436–446.
  5. Mesholam RI, Moberg PJ, Mahr RN, Doty RL: Olfaction in neurodegenerative disease: a meta-analysis of olfactory functioning in Alzheimer’s and Parkinson’s diseases. Arch Neurol 1998;55:84–90.
  6. Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E: Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 2003;24:197–211.
  7. Pearce RK, Hawkes CH, Daniel SE: The anterior olfactory nucleus in Parkinson’s disease. Mov Disord 1995;10:283–287.
  8. Duda JE: Pathology and neurotransmitter abnormalities of dementia with Lewy bodies. Dement Geriatr Cogn Disord 2004;17(suppl 1):3–14.
  9. Del Tredici K, Rub U, De Vos RA, Bohl JR, Braak H: Where does Parkinson disease pathology begin in the brain? J Neuropathol Exp Neurol 2002;61:413–426.
  10. Duda JE, Shah U, Arnold SE, Lee VM, Trojanowski JQ: The expression of α-, β-, and γ-synucleins in olfactory mucosa from patients with and without neurodegenerative diseases. Exp Neurol 1999;160:515–522.
  11. Braak H, Rub U, Gai WP, Del Tredici K: Idiopathic Parkinson’s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm 2003;110:517–536.
  12. Silveira-Moriyama L, Holton J, Kingsbury A, Ayling H. Petrie A, Sterlacci W, Poewe W, Maier H, Lees AJ, Revesz T: The primary olfactory cortex in idiopathic Parkinson’s disease (IPD) and incidental Lewy body disease (ILBD). Mov Disord 2007;22:S91.

    External Resources

  13. Hurtig HI, Trojanowski JQ, Galvin J, Ewbank D, Schmidt ML, Lee VM, Clark CM, Glosser G, Stern MB, Gollomp SM, Arnold SE: α-Synuclein cortical Lewy bodies correlate with dementia in Parkinson’s disease. Neurology 2000;54:1916–1921.
  14. 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.
  15. Doty RL, Stern MB, Pfeiffer C, Gollomp SM, Hurtig HI: Bilateral olfactory dysfunction in early stage treated and untreated idiopathic Parkinson’s disease. J Neurol Neurosurg Psychiatry 1992;55:138–142.
  16. 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.
  17. Hsia AY, Vincent JD, Lledo PM: Dopamine depresses synaptic inputs into the olfactory bulb. J Neurophysiol 1999;82:1082–1085.
  18. Duchamp-Viret P, Coronas V, Delaleu JC, Moyse E, Duchamp A: Dopaminergic modulation of mitral cell activity in the frog olfactory bulb: a combined radioligand binding-electrophysiological study. Neuroscience 1997;79:203–216.
  19. Koller WC, Langston JW, Hubble JP, Irwin I, Zack M, Golbe L, Forno L, Ellenberg J, Kurland L, Ruttenber AJ, et al: Does a long preclinical period occur in Parkinson’s disease? Geriatrics 1991;46(suppl 1):8–15.

    External Resources

  20. Wolters EC, Francot C, Bergmans P, Winogrodzka A, Booij J, Berendse HW, Stoof JC: Preclinical (premotor) Parkinson’s disease. J Neurol 2000;247(suppl 2):II103–II109.
  21. Horstink MW, Morrish PK: Preclinical diagnosis of Parkinson’s disease. Adv Neurol 1999;80:327–333.
  22. Doty RL, Shaman P, Kimmelman CP, Dann MS: University of Pennsylvania Smell Identification Test: a rapid quantitative olfactory function test for the clinic. Laryngoscope 1984;94:176–178.
  23. Bohnen NI, Gedela S, Kuwabara H, Constantine GM, Mathis CA, Studenski SA, Moore RY: Selective hyposmia and nigrostriatal dopaminergic denervation in Parkinson’s disease. J Neurol 2007;254:84–90.
  24. 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.
  25. Potagas C, Dellatolas G, Ziegler M, Leveteau J, Bathien N, Mac Leod P, Rondot P: Clinical assessment of olfactory dysfunction in Parkinson’s disease. Mov Disord 1998;13:394–399.
  26. Tissingh G, Berendse HW, Bergmans P, DeWaard R, Drukarch B, Stoof JC, Wolters EC: Loss of olfaction in de novo and treated Parkinson’s disease: possible implications for early diagnosis. Mov Disord 2001;16:41–46.
  27. Muller 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.
  28. Sobel N, Thomason ME, Stappen I, Tanner CM, Tetrud JW, Bower JM, Sullivan EV, Gabrieli JD: An impairment in sniffing contributes to the olfactory impairment in Parkinson’s disease. Proc Natl Acad Sci USA 2001;98:4154–4159.
  29. Thesen T, Murphy C: Reliability analysis of event-related brain potentials to olfactory stimuli. Psychophysiology 2002;39:733–738.
  30. 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.
  31. Lotsch J, Hummel T: The clinical significance of electrophysiological measures of olfactory function. Behav Brain Res 2006;170:78–83.
  32. Montgomery EB Jr, Lyons K, Koller WC: Early detection of probable idiopathic Parkinson’s disease. II. A prospective application of a diagnostic test battery. Mov Disord 2000;15:474–478.
  33. Lee PH, Yeo SH, Kim HJ, Youm HY: Correlation between cardiac 123I-MIBG and odor identification in patients with Parkinson’s disease and multiple system atrophy. Mov Disord 2006;21:1975–1977.
  34. Braune S, Reinhardt M, Bathmann J, Krause T, Lehmann M, Lucking CH: Impaired cardiac uptake of meta-[123I]iodobenzylguanidine in Parkinson’s disease with autonomic failure. Acta Neurol Scand 1998;97:307–314.
  35. Yoshita M: Differentiation of idiopathic Parkinson’s disease from striatonigral degeneration and progressive supranuclear palsy using iodine-123 meta-iodobenzylguanidine myocardial scintigraphy. J Neurol Sci 1998;155:60–67.
  36. 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: [99mTc]TRODAT-1 SPECT imaging correlates with odor identification in early Parkinson disease. Neurology 2005;64:1716–1720.
  37. Ponsen MM, Stoffers D, Booij J, van Eck-Smit BL, Wolters E, Berendse HW: Idiopathic hyposmia as a preclinical sign of Parkinson’s disease. Ann Neurol 2004;56:173–181.
  38. 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.
  39. Sommer U, Hummel T, Cormann K, Mueller A, Frasnelli J, Kropp J, Reichmann H: Detection of presymptomatic Parkinson’s disease: combining smell tests, transcranial sonography, and SPECT. Mov Disord 2004;19:1196–1202.
  40. 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.
  41. Suchowersky O, Reich S, Perlmutter J, Zesiewicz T, Gronseth G, Weiner WJ: Practice parameter: diagnosis and prognosis of new onset Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006;66:968–975.
  42. McShane RH, Nagy Z, Esiri MM, King E, Joachim C, Sullivan N, Smith AD: Anosmia in dementia is associated with Lewy bodies rather than Alzheimer’s pathology. J Neurol Neurosurg Psychiatry 2001;70:739–743.
  43. Olichney JM, Murphy C, Hofstetter CR, Foster K, Hansen LA, Thal LJ, Katzman R: Anosmia is very common in the Lewy body variant of Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2005;76:1342–1347.
  44. Hawkes C: Olfaction in neurodegenerative disorder. Mov Disord 2003;18:364–372.
  45. Katzenschlager R, Lees AJ: Olfaction and Parkinson’s syndromes: its role in differential diagnosis. Curr Opin Neurol 2004;17:417–423.
  46. Doty RL, Singh A, Tetrud J, Langston JW: Lack of major olfactory dysfunction in MPTP-induced parkinsonism. Ann Neurol 1992;32:97–100.
  47. Khan NL, Katzenschlager R, Watt H, Bhatia KP, Wood NW, Quinn N, Lees AJ: Olfaction differentiates parkin disease from early-onset parkinsonism and Parkinson disease. Neurology 2004;62:1224–1226.
  48. Hensiek AE, Bhatia K, Hawkes CH: Olfactory function in drug induced parkinsonism. J Neurol 2000;247:P303.

    External Resources

  49. Berendse HW, Booij J, Francot CM, Bergmans PL, Hijman R, Stoof JC, Wolters EC: Subclinical dopaminergic dysfunction in asymptomatic Parkinson’s disease patients’ relatives with a decreased sense of smell. Ann Neurol 2001;50:34–41.
  50. Marras C, Goldman S, Smith A, Barney P, Aston D, Comyns K, Korell M, Langston JW, Ross GW, Tanner CM: Smell identification ability in twin pairs discordant for Parkinson’s disease. Mov Disord 2005;20:687–693.
  51. Stern MB, Doty RL, Dotti M, Corcoran P, Crawford D, McKeown DA, Adler C, Gollomp S, Hurtig H: Olfactory function in Parkinson’s disease subtypes. Neurology 1994;44:266–268.
  52. Hummel T: Olfactory evoked potentials as a tool to measure progression of Parkinson’s Disease; in Chase T, Bedard B (eds): Focus on Medicine: New Developments in the Drug Therapy of Parkinson’s Disease. Oxford, Blackwell Science, 1999, vol 14, pp 47–53.
  53. Siderowf A, Stern MB: Preclinical diagnosis of Parkinson’s disease: are we there yet? Curr Neurol Neurosci Rep 2006;6:295–301.