Document Type : Review Article

Authors

1 Isfahan Neurosciences Research Center, Isfahan University of medical sciences, Isfahan, Iran.

2 Anesthesiology department, School of medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

3 Multiple Sclerosis Research Center, Neuroscience institute, Tehran University of Medical Sciences, Tehran, Iran. Universal Council of Epidemiology (UCE), Universal Scientific Education and Research Network (USERN), Tehran University

4 Functional Neurosurgery Research Center, Shohada Tajrish Neurosurgical Comprehensive Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran

5 Department of Neurology, School of medicine, Isfahan University of medical sciences, Isfahan, Iran

Abstract

Background: Parkinson’s disease (PD) is a progressive neuro-degenerative disease and olfactory dysfunction is considered as an important issue in these patients. The prevalence of olfactory dysfunction in patients with PD was reported variously in previous studies. Therefore, we designed this systematic review and meta-analysis to estimate the pooled prevalence of olfactory dysfunction in patients with PD.
Methods: Two expert researchers systematically searched PubMed, Scopus, EMBASE, Web of Science, Google Scholar, references of the papers, and conference abstracts. The titles and abstracts of the potential studies were evaluated after deleting the duplicates. We extracted data regarding the total number of participants, first author, publication year, the country of origin, mean age, mean disease duration, female/male, number with olfactory dysfunction, and name of the test. We evaluated the risk of potential bias by the Newcastle-Ottawa Quality Assessment Scale (adapted for cross-sectional studies). All statistical analyses were done using Stata software. To determine heterogeneity between the findings of included studies, inconsistency (I2) was calculated. We applied random effect model when I2 was more than 50%. P-value less than 0.05 was considered significant. 
Results: The literature search revealed 1546 studies; after deleting duplicates, 894 remained. Finally, twelve studies remained for meta-analysis. Studies were published between years of 2009 to 2021, the sample size of studies ranged between 30 and 2097, and the mean age ranged between 61 and 70 years. The pooled prevalence of olfactory dysfunction in patients with PD was estimated as 64% [95% confidence interval (CI): 44-84, I2 = 99.7%, P < 0.001]. The pooled prevalence of olfactory dysfunction using Sniffin's test was 67% (95% CI: 51-83) and using other tests was 60% (95% CI: 28-92).
Conclusion: The results of this systematic review and meta-analysis showed that the pooled prevalence of olfactory dysfunction in patients with PD was 64% which should be considered by physicians.

Keywords

  1. Kanavou S, Pitz V, Lawton MA, Malek N, Grosset KA, Morris HR, et al. Comparison between four published definitions of hyposmia in Parkinson's disease. Brain Behav 2021; 11(8): e2258.
  2. Khoshnood RJ, Zali A, Tafreshinejad A, Ghajarzadeh M, Ebrahimi N, Safari S,
    et al. Parkinson's disease and COVID-19: A systematic review and meta-analysis. Neurol Sci 2022; 43(2): 775-83.
  3. Chaudhuri KR, Healy DG, Schapira AH. Non-motor symptoms of Parkinson's disease: Diagnosis and management. Lancet Neurol 2006; 5(3): 235-45.
  4. Magerkurth C, Schnitzer R, Braune S. Symptoms of autonomic failure in Parkinson's disease: Prevalence and impact on daily life. Clin Auton Res 2005; 15(2): 76-82.
  5. Martinez-Martin P, Schapira AH, Stocchi F, Sethi K, Odin P, MacPhee G, et al. Prevalence of nonmotor symptoms in Parkinson's disease in an international setting; study using nonmotor symptoms questionnaire in 545 patients. Mov Disord 2007; 22(11): 1623-9.
  6. Kalf JG, de Swart BJ, Borm GF, Bloem BR, Munneke M. Prevalence and definition of drooling in Parkinson's disease: A systematic review. J Neurol 2009; 256(9): 1391-6.
  7. 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(8): 1237-44.
  8. Tinazzi M, Del VC, Fincati E, Ottaviani S, Smania N, Moretto G, et al. Pain and motor complications in Parkinson's disease. J Neurol Neurosurg Psychiatry 2006; 77(7): 822-5.
  9. Ansari KA, Johnson A. Olfactory function in patients with Parkinson's disease. J Chronic Dis 1975; 28(9): 493-7.
  10. Ward CD, Hess WA, Calne DB. Olfactory impairment in Parkinson's disease. Neurology 1983; 33(7): 943-6.
  11. Korten JJ, Meulstee J. Olfactory disturbances in Parkinsonism. Clin Neurol Neurosurg 1980; 82(2): 113-8.
  12. Ross GW, Petrovitch H, Abbott RD, Tanner CM, Popper J, Masaki K, et al. Association of olfactory dysfunction with risk for future Parkinson's disease. Ann Neurol 2008; 63(2): 167-73.
  13. Domellof ME, Lundin KF, Edstrom M, Forsgren L. Olfactory dysfunction and dementia in newly diagnosed patients with Parkinson's disease. Parkinsonism Relat Disord 2017; 38: 41-7.
  14. Wattendorf E, Welge-Lussen A, Fiedler K, Bilecen D, Wolfensberger M, Fuhr P, et al. Olfactory impairment predicts brain atrophy in Parkinson's disease. J Neurosci 2009; 29(49): 15410-3.
  15. Modesti PA, Reboldi G, Cappuccio FP, Agyemang C, Remuzzi G, Rapi S, et al. Panethnic differences in blood pressure in Europe: A systematic review and meta-analysis. PLoS One 2016; 11(1): e0147601.
  16. Camargo CHF, Jobbins VA, Serpa RA, Berbetz FA, Sabatini JS, Teive HAG. Association between olfactory loss and cognitive deficits in Parkinson's disease. Clin Neurol Neurosurg 2018; 173: 120-3.
  17. Haehner A, Boesveldt S, Berendse HW, Mackay-Sim A, Fleischmann J, Silburn PA, et al. Prevalence of smell loss in Parkinson's disease--a multicenter study. Parkinsonism Relat Disord 2009; 15(7): 490-4.
  18. Casjens S, Eckert A, Woitalla D, Ellrichmann G, Turewicz M, Stephan C, et al. Diagnostic value of the impairment of olfaction in Parkinson's disease. PLoS One 2013; 8(5): e64735.
  19. Haugen J, Muller ML, Kotagal V, Albin RL, Koeppe RA, Scott PJ, et al. Prevalence of impaired odor identification in Parkinson disease with imaging evidence of nigrostriatal denervation. J Neural Transm (Vienna) 2016; 123(4): 421-4.
  20. Roos DS, Twisk JWR, Raijmakers PGHM, Doty RL, Berendse HW. Hyposmia as a marker of (non-)motor disease severity in Parkinson's disease. J Neural Transm (Vienna) 2019; 126(11): 1471-8.
  21. Kulick CV, Montgomery KM, Nirenberg MJ. Comprehensive identification of delusions and olfactory, tactile, gustatory, and minor hallucinations in Parkinson's disease psychosis. Parkinsonism Relat Disord 2018; 54: 40-5.
  22. Krismer F, Pinter B, Mueller C, Mahlknecht P, Nocker M, Reiter E, et al. Sniffing the diagnosis: Olfactory testing in neurodegenerative parkinsonism. Parkinsonism Relat Disord 2017; 35: 36-41.
  23. Zhang TM, Yu SY, Guo P, Du Y, Hu Y, Piao YS, et al. Nonmotor symptoms in patients with Parkinson disease: A cross-sectional observational study. Medicine (Baltimore) 2016; 95(50): e5400.
  24. Lopez HN, Garcia EA, Shalabi BM. Diagnostic value of combined assessment of olfaction and sustantia nigra hyperechogenicity for Parkinson's disease. Neurologia 2015; 30(8): 496-501.
  25. Muller B, Larsen JP, Wentzel-Larsen T, Skeie GO, Tysnes OB. Autonomic and sensory symptoms and signs in incident, untreated Parkinson's disease: Frequent but mild. Mov Disord 2011; 26(1): 65-72.
  26. Rumeau C, Nguyen DT, Jankowski R. How to assess olfactory performance with the Sniffin' Sticks test (®). Eur Ann Otorhinolaryngol Head Neck Dis 2016; 133(3): 203-6.
  27. Seubert J, Laukka EJ, Rizzuto D, Hummel T, Fratiglioni L, Backman L, et al. Prevalence and correlates of olfactory dysfunction in old age: A population-based study. J Gerontol A Biol Sci Med Sci 2017; 72(8): 1072-9.
  28. Stern MB, Doty RL, Dotti M, Corcoran P, Crawford D, McKeown DA, et al. Olfactory function in Parkinson's disease subtypes. Neurology 1994; 44(2): 266-8.
  29. Hummel T. Olfactory evoked potentials as a tool to measure progression of Parkinson's disease. Focus on medicine 1999; 14: 47-53.
  30. Boesveldt S, Verbaan D, Knol DL, Visser M, van Rooden SM, van Hilten JJ, et al. A comparative study of odor identification and odor discrimination deficits in Parkinson's disease. Mov Disord 2008; 23(14): 1984-90.
  31. Bohnen NI, Gedela S, Kuwabara H, Constantine GM, Mathis CA, Studenski SA, et al. Selective hyposmia and nigrostriatal dopaminergic denervation in Parkinson's disease. J Neurol 2007; 254(1): 84-90.
  32. Hanganu A, Monchi O. Structural neuroimaging markers of cognitive decline in Parkinson's disease. Parkinsons Dis 2016; 2016: 3217960.
  33. Damholdt MF, Borghammer P, Larsen L, Ostergaard K. Odor identification deficits identify Parkinson's disease patients with poor cognitive performance. Mov Disord 2011; 26(11): 2045-50.
  34. Fullard ME, Tran B, Xie SX, Toledo JB, Scordia C, Linder C, et al. Olfactory impairment predicts cognitive decline in early Parkinson's disease. Parkinsonism Relat Disord 2016; 25: 45-51.