Skip to main content
Log in

Olfactory dysfunction and cardiovascular dysautonomia in Parkinson’s disease

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Several studies have reported that olfactory dysfunction is an early neuropathological manifestation of Parkinson’s disease (PD). Reduced cardiac meta-iodobenzylguanidine (123I-MIBG) uptake may be one of the earliest signs of PD. We studied the relation of olfactory dysfunction to cardiovascular dysautonomia in patients with PD. The study group comprised 66 patients with PD (70.5 years) and 26 controls (70.3 years) for olfactory assessment, 21 controls (72.1 years) for cardiac 123I-MIBG scintigraphy and heart rate variability (HRV), assessed using the coefficient of variation for RR intervals (HRV), and 23 controls (69.2 years) for orthostatic blood pressure response. Olfactory function was assessed by the odor stick identification test Japan (OSIT-J), and cardiovascular autonomic function was evaluated by 123I-MIBG scintigraphy of the heart, the fall in orthostatic blood pressure, and HRV. Patients with PD had a significantly lower OSIT-J score than did the controls (4.1 ± 3.0 vs. 9.9 ± 1.7, p = 0.001). The OSIT-J score was unrelated to variables other than gender, including age, disease duration, motor score on the unified Parkinson’s disease rating scale, score on the mini-mental state examination, motor phenotype, visual hallucinations, and dopaminergic medication on multiple regression and logistic regression analyses. The OSIT-J score was related to the heart/mediastinum ratio of cardiac 123I-MIBG uptake, the fall in orthostatic blood pressure, and HRV, after adjustment for other clinical variables. Olfactory dysfunction in PD was, thus, significantly related to both cardiac sympathetic and parasympathetic dysfunction, as well as vascular sympathetic dysfunction. As non-motor symptoms of PD, olfactory dysfunction and autonomic network failure appear to be closely related in PD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Benarroch EE, Schmeichel AM, Parisi JE (2003) Preservation of brachiomotor neurons of the nucleus ambiguus in multiple system atrophy. Neurology 60:115–117

    PubMed  Google Scholar 

  2. Benarroch EE, Schmeichel AM, Sandroni P, Low PA, Parisi JE (2006) Involvement of vagal autonomic nuclei in multiple system atrophy and Lewy body diseases. Neurology 66:378–383

    Article  CAS  PubMed  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. Chaudhuri KR, Healy DG, Schapira AH (2006) Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol 5:235–245

    Article  PubMed  Google Scholar 

  5. Cheng Z, Powley TL (2000) Nucleus ambiguus projections to cardiac ganglia of rat atria: an antegrade tracing study. J Comp Neurol 424:588–606

    Article  CAS  PubMed  Google Scholar 

  6. Churchyard A, Mathias CJ, Phil D, Lees AJ (1999) Selegiline-induced postural hypotension in Parkinson’s disease: a longitudinal study on the effects of drug withdrawal. Mov Disord 14:246–251

    Article  CAS  PubMed  Google Scholar 

  7. Deep Brain Stimulation for Parkinson’s Disease Study Group (2001) Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson’s disease. N Engl J Med 345:956–963

    Article  Google Scholar 

  8. Devos D, Kroumova M, Bordet H, Vodougnon JD, Guieu JD, Libersa C et al (2003) Heart rate variability and Parkinson’s disease severity. J Neural Transm 110:997–1011

    Article  CAS  PubMed  Google Scholar 

  9. Doty RL, Shaman P, Applebaum SL, Giberson R, Siksorski L, Rosenberg L (1984) Smell identification ability: changes with age. Science 226:1441–1443

    Article  CAS  PubMed  Google Scholar 

  10. 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

    CAS  PubMed  Google Scholar 

  11. Doty RL, Riklan M, Deems DA, Reynolds C, Stellar S (1989) The olfactory and cognitive deficits of Parkinson’s disease: evidence for independence. Ann Neurol 25:166–171

    Article  CAS  PubMed  Google Scholar 

  12. Emilien G, Maloteaux JM, Geurts M, Hoogenberg K, Cragg S (1999) Dopamine receptors––physiological understanding to therapeutic intervention potential. Pharmacol Ther 84:133–156

    Article  CAS  PubMed  Google Scholar 

  13. Fahn S, Elton RL, Members of the UPDRS committee (1987) Unified Parkinson’s disease rating scale. In: Fahn S, Marsden CD, Calne DB, Goldstein M (eds) Recent developments in Parkinson’s disease. Macmillan Healthcare information, Florham Park, pp 153–163

    Google Scholar 

  14. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state” A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198

    Article  CAS  PubMed  Google Scholar 

  15. Frye RE, Schwartz BS, Doty RL (1990) Dose-related effects of cigarette smoking on olfactory function. JAMA 263:1233–1236

    Article  CAS  PubMed  Google Scholar 

  16. Goldberg LI (1964) Monoamine oxidase inhibitors: adverse reactions and possible mechanisms. JAMA 190:456–462

    CAS  PubMed  Google Scholar 

  17. Goldstein DS, Eldadah BA, Holmes C, Pechnik S, Moak J, Saleem A et al (2005) Neurocirculatory abnormalities in Parkinson disease with orthostatic hypotension: independence from levodopa treatment. Hypertension 46:1333–1339

    Article  CAS  PubMed  Google Scholar 

  18. Goldstein DS (2003) Dysautonomia in Parkinson’s disease: neurocardiological abnormalities. Lancet Neurol 2:669–676

    Article  PubMed  Google Scholar 

  19. Goldstein DS, Sewell L (2009) Olfactory dysfunction in pure autonomic failure: implications for the pathogenesis of Lewy body diseases. Parkinsonism Relat Disord 15:516–520

    Article  PubMed  Google Scholar 

  20. Grosset K, Needleman F, Macphee G, Grosset D (2004) Switching from ergot to nonergot dopamine agonists in Parkinson’s disease: a clinical series and five-drug dose conversion table. Mov Disord 19:1370–1374

    Article  PubMed  Google Scholar 

  21. 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 22:839–842

    Article  PubMed  Google Scholar 

  22. Haensch CA, Lerch H, Jörg J, Isenmann S (2009) Cardiac denervation occurs independent of orthostatic hypotension and impaired heart rate variability in Parkinson’s disease. Parkinsonism Relat Disord 15:134–137

    Article  PubMed  Google Scholar 

  23. Hashimoto Y, Fukazawa K, Fujii M, Takayasu S, Muto T, Saito S et al (2004) Usefulness of the odor stick identification test for Japanese patients with olfactory dysfunction. Chem Senses 29:565–571

    Article  PubMed  Google Scholar 

  24. Hawkes CH (2008) Parkinson’s disease and aging: same or different process? Mov Disord 23:47–52

    Article  PubMed  Google Scholar 

  25. Hobson DE, Pourcher E, Martin WR (1999) Ropinirole and pramipexole, the new agonists. Can J Neurol Sci 26(Suppl 2):S27–S33

    PubMed  Google Scholar 

  26. Holroyd S, Keller AS (1995) A study of visual hallucinations in Alzheimer’s disease. Am J Geriatr Psychiatry 3:198–205

    Article  Google Scholar 

  27. 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 Psychiatr 55:181–184

    Article  CAS  PubMed  Google Scholar 

  28. Iijima M, Kobayakawa T, Saito S, Osawa M, Tsutsumi Y, Hashimoto S, Iwata M (2008) Smell identification in Japanese Parkinson’s disease patients: using the odor stick identification test for Japanese subjects. Intern Med 47:1887–1892

    Article  PubMed  Google Scholar 

  29. Iwanaga K, Wakabayashi K, Yoshimoto M, Tomita I, Satoh H, Takashima H et al (1999) Lewy body-type degeneration in cardiac plexus in Parkinson’s and incidental Lewy body diseases. Neurology 52:1269–1271

    CAS  PubMed  Google Scholar 

  30. Jones BE, Yang TZ (1985) The efferent projections from the reticular formation and the locus coeruleus studied by anterograde and retrograde axonal transport in the rat. J Comp Neurol 242:56–92

    Article  CAS  PubMed  Google Scholar 

  31. Kaufmann H (1996) Consensus statement on the definition of orthostatic hypotension, pure autonomic failure and multiple system atrophy. Clin Auton Res 6:125–126

    Article  CAS  PubMed  Google Scholar 

  32. Kawamura H, Gunn CG, Frohlich ED (1978) Cardiovascular alterations by nucleus locus coeruleus in the spontaneously hypertensive rat. Brain Res 140:137–147

    Article  CAS  PubMed  Google Scholar 

  33. Kobal G, Hummel T, Sekinger B, Barz S, Roscher S, Wolf S (1996) “Sniffin Sticks”: screening of olfactory performance. Rhinology 34:222–226

    CAS  PubMed  Google Scholar 

  34. Lee PH, Yeo SH, Kim HJ, Youm HY (2006) Correlation between cardiac 123I-MIBG and odor identification in patients with Parkinson’s disease and multiple system atrophy. Mov Disord 21:1975–1977

    Article  PubMed  Google Scholar 

  35. Lode HN, Bruchelt G, Seitz G, Gebhardt S, Gekeler V, Niethammer D et al (1995) Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of monoamine transporters in neuroblastoma cell lines: correlations to meta-iodobenzylguanidine (MIBG) uptake and tyrosine hydroxylase gene expression. Eur J Cancer 31A:586–590

    Article  CAS  PubMed  Google Scholar 

  36. Mathias CJ, Bannister RS (1999) Autonomic failure: a textbook of clinical disorders of the autonomic nervous system, 4th edn. Oxford University Press, New York

    Google Scholar 

  37. Miyamoto T, Miyamoto M, Iwanami M, Suzuki K, Inoue Y, Hirata K (2009) Odor identification test as an indicator of idiopathic REM sleep behavior disorder. Mov Disord 24:268–273

    Article  PubMed  Google Scholar 

  38. Oishi N, Udaka F, Kameyama M, Sawamoto N, Hashikawa K, Fukuyama H (2005) Regional cerebral blood flow in Parkinson disease with nonpsychotic visual hallucinations. Neurology 65:1708–1715

    Article  CAS  PubMed  Google Scholar 

  39. Oka H, Mochio S, Sato H, Katayama K (1997) Prolongation of QTc interval in patients with Parkinson’s disease. Eur Neurol 37:186–189

    Article  CAS  PubMed  Google Scholar 

  40. Oka H, Mochio S, Yoshioka M, Morita M, Inoue K (2003) Evaluation of baroreflex sensitivity by the sequence method using blood pressure oscillations and R–R interval changes during deep respiration. Eur Neurol 50:230–243

    Article  PubMed  Google Scholar 

  41. Okada Y, Ito Y, Aida J, Yasuhara M, Ohkawa S, Hirokawa K (2004) Lewy bodies in the sinoatrial nodal ganglion: clinicopathological studies. Pathol Int 54:682–687

    Article  PubMed  Google Scholar 

  42. Orimo S, Ozawa E, Nakade S, Sugimoto T, Mizusawa H (1999) [123] I-metaiodobenzylguanidine myocardial scintigraphy in Parkinson’s disease. J Neurol Neurosurg Psychiatry 67:189–194

    Article  CAS  PubMed  Google Scholar 

  43. Orimo S, Amino T, Itoh Y, Takahashi A, Kojo T, Uchihara T et al (2005) Cardiac sympathetic denervation precedes neuronal loss in the sympathetic ganglia in Lewy body disease. Acta Neuropathol 109:583–588

    Article  PubMed  Google Scholar 

  44. Orimo S, Takahashi A, Uchihara T, Mori F, Kakita A, Wakabayashi K et al (2007) Degeneration of cardiac sympathetic nerve begins in the early disease process of Parkinson’s disease. Brain Pathol 17:24–30

    Article  CAS  PubMed  Google Scholar 

  45. Orimo S, Uchihara T, Nakamura A, Mori F, Kakita A, Wakabayashi K et al (2008) Axonal alpha-synuclein aggregates herald centripetal degeneration of cardiac sympathetic nerve in Parkinson’s disease. Brain 131:642–650

    Article  PubMed  Google Scholar 

  46. Rajput AH, Rozdilsky B (1976) Dysautonomia in Parkinsonism: a clinicopathological study. J Neurol Neurosurg Psychiatry 39:1092–1100

    Article  CAS  PubMed  Google Scholar 

  47. Robertson D, Hollister AS, Biaggioni I, Netterville JL, Mosqueda-Garcia R, Robertson RM (1993) The diagnosis and treatment of baroreflex failure. N Engl J Med 329:1449–1455

    Article  CAS  PubMed  Google Scholar 

  48. Saito S, Ayabe-Kanamura S, Takashima Y, Gotow N, Naito N, Nozawa T et al (2006) Development of a smell identification test using a novel stick-type odor presentation kit. Chem Sense 31:379–391

    Article  Google Scholar 

  49. Senard JM, Raï S, Lapeyre-Mestre M, Brefel C, Rascol O, Rascol A et al (1997) Prevalence of orthostatic hypotension in Parkinson’s disease. J Neurol Neurosurg Psychiatry 63:584–589

    Article  CAS  PubMed  Google Scholar 

  50. Shibata M, Morita Y, Shimizu T, Takahashi K, Suzuki N (2009) Cardiac parasympathetic dysfunction concurrent with cardiac sympathetic denervation in Parkinson’s disease. J Neurol Sci 276:79–83

    Article  PubMed  Google Scholar 

  51. Solanki KK, Bomanji J, Moyes J, Mather SJ, Trainer PJ, Britton KE (1992) A pharmacological guide to medicines which interfere with the biodistribution of radiolabelled meta-iodobenzylguanidine (MIBG). Nucl Med Commun 13:513–521

    Article  CAS  PubMed  Google Scholar 

  52. Spiegel J, Mollers MO, Jost WH, Fuss G, Samnick S, Dillmann U et al (2005) FP-CIT and MIBG scintigraphy in early Parkinson’s disease. Mov Disord 20:552–561

    Article  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  54. Task Force of the European Society of Cardiology, the North American Society of Pacing, Electrophysiology (1996) Heart rate variability: standards of measurement, physiological interpretation, and clinical use. Eur Heart J 17:354–381

    Google Scholar 

  55. Tateno F, Sakakibara R, Saiki A, Miyashita Y, Shirai K (2008) Levodopa might affect metaiodobenzylguanidine myocardial accumulation. Mov Disord 23:2097–2098

    PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  57. Thuerauf N, Reulbach U, Lunkenheimer J, Lunkenheimer B, Spannenberger R, Gossler A et al (2009) Emotional reactivity to odors: olfactory sensitivity and the span of emotional evaluation separate the genders. Neurosci Lett 456:74–79

    Article  CAS  PubMed  Google Scholar 

  58. Ward DG, Gunn CG (1976) Locus coeruleus complex: different modulation of depressor mechanism. Brain Res 107:407–411

    Article  CAS  PubMed  Google Scholar 

  59. Wheeler T, Watkins PJ (1973) Cardiac denervation in diabetes. Br Med J 4:584–586

    Article  CAS  PubMed  Google Scholar 

  60. Williams SS, J Williams J, Combrinck M, Christie S, Smith AD, McShane R (2009) Olfactory impairment is more marked in patients with mild dementia with Lewy bodies than those with mild Alzheimer disease. J Neurol Neurosurg Psychiatry 80:667–670

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hisayoshi Oka.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oka, H., Toyoda, C., Yogo, M. et al. Olfactory dysfunction and cardiovascular dysautonomia in Parkinson’s disease. J Neurol 257, 969–976 (2010). https://doi.org/10.1007/s00415-009-5447-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-009-5447-1

Keywords

Navigation