AccScience Publishing / AN / Online First / DOI: 10.36922/AN025110024
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ORIGINAL RESEARCH ARTICLE

The most significant brain regions implicated in olfactory dysfunction in Parkinson’s disease

Naser Moradi1 ,  Siamak Shahidi2* ,  Bahareh Zaker Harofteh3* ,  Mohammad Ahmadpanah4 ,  Sajjad Farashi2 ,  Ghodratollah Roshanaei5
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1 Department of Neuroscience, School of Science and Advanced Technologies in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
2 Neurophysiology Research Center, Institute of Neuroscience and Mental Health, Avicenna Health Research Institute, Hamadan University of Medical Sciences, Hamadan, Iran
3 Department of Neurological Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4 Behavioral Disorders and Substance Abuse Research Center, Institute of Neuroscience and Mental Health, Avicenna Health Research Institute, Hamadan University of Medical Sciences, Hamadan
5 Department of Biostatistics, School of Medicine, Arak University of Medical Sciences, Arak, Iran
Advanced Neurology, 025110024 https://doi.org/10.36922/AN025110024
Received: 16 March 2025 | Revised: 12 April 2025 | Accepted: 17 April 2025 | Published online: 20 May 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Olfactory dysfunction is observed in over 95% of patients with Parkinson’s disease (PD). This study examines the relationship between gray matter volume (GMV) and olfactory impairment in a cohort of 182 subjects, including PD patients and healthy controls (HCs). Using the Iran Smell Identification Test, which is a standardized 24-item olfactory identification assessment, to evaluate the olfactory performance, PD patients were divided into two groups (scores ranging from 0 to 18 indicate olfactory dysfunction, while scores from 19 to 24 indicate normal olfaction): those with normal smell (PD-NS, n = 23) and those with smell disorders (PD-SD, n = 69). Differences in GMV were analyzed using voxel-based morphometry. Statistical analysis was conducted using SPSS 26. The results revealed that the PD-NS group exhibited reduced GMV in the right thalamus and the left parahippocampal gyrus compared to the HCs. Furthermore, the HC group demonstrated no statistically significant olfactory dysfunction. In contrast, the PD-SD group showed significant decreases in GMV in the right entorhinal cortex and both the right and left hippocampus compared to both the HC and PD-NS groups. These findings indicate that PD patients experience more severe olfactory dysfunction in hippocampal regions than the HC group, likely attributed to the initial pathological loss of gray matter in both the right and left hippocampus.

Keywords
Parkinson’s disease
Smell
Gray matter
MRI
Brain volumetry
Funding
The authors are grateful for the technical assistance and financial support of Hamadan University of Medical Sciences (project code: 140203091653) and would like to thank the Clinical Research Development Unit of Hamadan University of Medical Sciences, Hamadan, Iran.
Conflict of interest
The authors declared that they have no competing interests.
References
  1. 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):1237-1244. doi: 10.1212/WNL.38.8.1237

 

  1. Hawkes CH, Shephard BC, Daniel SE. Is Parkinson’s disease a primary olfactory disorder? Qjm Int J Med. 1999;92(8):473-480. doi: 10.1093/qjmed/92.8.473

 

  1. Pont‐Sunyer C, Hotter A, Gaig C, et al. The onset of nonmotor symptoms in Parkinson’s disease (The ONSET PD Study). Mov Disord. 2015;30(2):229-237. doi: 10.1002/mds.26077

 

  1. Hummel T, Nordin S. Olfactory disorders and their consequences for quality of life. Acta Otolaryngol. 2005;125(2):116-121. doi: 10.1080/00016480410022787

 

  1. Politis M, Wu K, Molloy S, Bain PG, Chaudhuri KR, Piccini P. Parkinson’s disease symptoms: The patient’s perspective. Mov Disord. 2010;25(11):1646-1651. doi: 10.1002/mds.23135

 

  1. Munhoz RP, Moro A, Silveira-Moriyama L, Teive HA. Non-motor signs in Parkinson’s disease: A review. Arq Neuropsiquiatr. 2015;73:454-462. doi: 10.1590/0004-282X20150029

 

  1. Tissingh G, Berendse HW, Bergmans P, et al. Loss of olfaction in de novo and treated Parkinson’s disease: Possible implications for early diagnosis. Move Disord. 2001;16(1):41-46. doi: 10.1002/1531-8257(200101)16:1<41:AID-MDS1017> 3.0.CO;2-M

 

  1. Barresi M, Ciurleo R, Giacoppo S, et al. Evaluation of olfactory dysfunction in neurodegenerative diseases. J Neurol Sci. 2012;323(1-2):16-24. doi: 10.1016/j.jns.2012.08.028

 

  1. Gottfried JA. Central mechanisms of odour object perception. Nat Rev Neurosci. 2010;11(9):628-641. doi: 10.1038/nrn2883

 

  1. Kadohisa M, Wilson DA. Separate encoding of identity and similarity of complex familiar odors in piriform cortex. Proc Natl Acad Sci U S A. 2006;103(41):15206-15211. doi: 10.1073/pnas.0604313103

 

  1. Staubli U, Fraser D, Kessler M, Lynch G. Studies on retrograde and anterograde amnesia of olfactory memory after denervation of the hippocampus by entorhinal cortex lesions. Behav Neural Biol. 1986;46(3):432-444. doi: 10.1016/S0163-1047(86)90464-4

 

  1. Wilson DA, Xu W, Sadrian B, Courtiol E, Cohen Y, Barnes DC. Cortical odor processing in health and disease. Prog Brain Res. 2014;208:275-305. doi: 10.1016/B978-0-444-63350-7.00011-5

 

  1. Jones-Gotman M, Zatorre RJ. Odor recognition memory in humans: Role of right temporal and orbitofrontal regions. Brain Cogn. 1993;22(2):182-198. doi: 10.1006/brcg.1993.1033

 

  1. Zatorre RJ, Jones-Gotman M, Evans AC, Meyer E. Functional localization and lateralization of human olfactory cortex. Nature. 1992;360(6402):339-340. doi: 10.1038/360339a0

 

  1. Plailly J, Howard JD, Gitelman DR, Gottfried JA. Attention to odor modulates thalamocortical connectivity in the human brain. J Neurosci. 2008;28(20):5257-5267. doi: 10.1523/JNEUROSCI.5607-07.2008

 

  1. Gao Y, Nie K, Huang B, et al. Changes of brain structure in Parkinson’s disease patients with mild cognitive impairment analyzed via VBM technology. Neurosci Lett. 2017;658:121-132. doi: 10.1016/j.neulet.2017.08.028

 

  1. Tessitore A, Santangelo G, De Micco R, et al. Cortical thickness changes in patients with Parkinson’s disease and impulse control disorders. Parkinsonism Relat Disord. 2016;24:119-125. doi: 10.1016/j.parkreldis.2015.10.013

 

  1. Möller C, Hafkemeijer A, Pijnenburg YA, et al. Different patterns of cortical gray matter loss over time in behavioral variant frontotemporal dementia and Alzheimer’s disease. Neurobiol Aging. 2016;38:21-31. doi: 10.1016/j.neurobiolaging.2015.10.020

 

  1. Ashburner J, Friston KJ. Voxel-based morphometry--the methods. Neuroimage. 2000;11(6):805-821. doi: 10.1006/nimg.2000.0582

 

  1. Chapleau M, Aldebert J, Montembeault M, Brambati SM. Atrophy in Alzheimer’s disease and semantic dementia: An ALE meta-analysis of voxel-based morphometry studies. J Alzheimers Dis. 2016;54(3):941-955. doi: 10.3233/JAD-160382

 

  1. Matsuda H. MRI morphometry in Alzheimer’s disease. Ageing Res Rev. 2016;30:17-24. doi: 10.1016/j.arr.2016.01.003

 

  1. Serra L, Cercignani M, Lenzi D, et al. Grey and white matter changes at different stages of Alzheimer’s disease. J Alzheimers Dis. 2010;19(1):147-159. doi: 10.3233/JAD-2010-1223

 

  1. Moradi N, Shahidi S, Ahmadpanah M, Farashi S, Roshanaei G. Cortical and subcortical gray matter volume and cognitive impairment in Parkinson’s disease. Appl Neuropsychol Adult. 2024;31:1-14. doi: 10.1080/23279095.2024.2443591

 

  1. Taherkhani S, Moztarzadeh F, Seraj J, et al. Iran smell identification test (Iran-SIT): A modified version of the university of pennsylvania smell identification test (UPSIT) for iranian population. Chem Percept. 2015;8(4):183-191. doi: 10.1007/s12078-015-9192-9

 

  1. Gaser C, Dahnke R, Thompson PM, Kurth F, Luders E, The Alzheimer’s Disease Neuroimaging Initiative. CAT: A computational anatomy toolbox for the analysis of structural MRI data. Gigascience. 2024;13:giae049. doi: 10.1093/gigascience/giae049

 

  1. Ashburner J, Friston KJ. Unified segmentation. Neuroimage. 2005;26(3):839-851. doi: 10.1016/j.neuroimage.2005.02.018

 

  1. Ashburner J. A fast diffeomorphic image registration algorithm. Neuroimage. 2007;38(1):95-113. doi: 10.1016/j.neuroimage.2007.07.007

 

  1. Lee S, Kim SS, Tae WS, et al. Regional volume analysis of the Parkinson disease brain in early disease stage: Gray matter, white matter, striatum, and thalamus. AJNR Am J Neuroradiol. 2011;32(4):682-687. doi: 10.3174/ajnr.A2372

 

  1. Halliday GM. Thalamic changes in Parkinson’s disease. Parkinsonism Relat Dis. 2009;15:S152-S155. doi: 10.1016/S1353-8020(09)70804-1

 

  1. Xia J, Wang J, Tian W, et al. Magnetic resonance morphometry of the loss of gray matter volume in Parkinson’s disease patients. Neural Regen Res. 2013;8(27):2557-2565. doi: 10.3969/j.issn.1673-5374.2013.27.007

 

  1. Gottfried JA, Zald DH. On the scent of human olfactory orbitofrontal cortex: Meta-analysis and comparison to non-human primates. Brain Res Brain Res Rev. 2005;50(2):287-304. doi: 10.1016/j.brainresrev.2005.08.004

 

  1. Braak H, Del Tredici K, Rüb U, De Vos RA, Steur ENJ, Braak E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging. 2003;24(2):197-211. doi: 10.1016/s0197-4580(02)00065-9

 

  1. Braak H, Bohl JR, Müller CM, Rüb U, De Vos RA, Del Tredici K. Stanley fahn lecture 2005: The staging procedure for the inclusion body pathology associated with sporadic Parkinson’s disease reconsidered. Move Disord. 2006;21(12):2042-2051. doi: 10.1002/mds.21065

 

  1. Silveira-Moriyama L, Holton JL, Kingsbury A, et al. Regional differences in the severity of Lewy body pathology across the olfactory cortex. Neurosci Lett. 2009;453(2):77-80. doi: 10.1016/j.neulet.2009.02.006

 

  1. Li Y, Xu J, Liu Y, et al. A distinct entorhinal cortex to hippocampal CA1 direct circuit for olfactory associative learning. Nat Neurosci. 2017;20(4):559-570. doi: 10.1038/nn.4517

 

  1. Bohnen NI, Gedela S, Herath P, Constantine GM, Moore RY. Selective hyposmia in Parkinson disease: Association with hippocampal dopamine activity. Neurosci Lett. 2008;447(1):12-16. doi: 10.1016/j.neulet.2008.09.070

 

  1. Roh H, Kang J, Koh SB, Kim JH. Hippocampal volume is related to olfactory impairment in Parkinson’s disease. J Neuroimaging. 2021;31(6):1176-1183. doi: 10.1111/jon.12911

 

  1. Barrett MJ, Murphy JM, Zhang J, et al. Olfaction, cholinergic basal forebrain degeneration, and cognition in early Parkinson disease. Parkinsonism Relat Disord. 2021;90:27-32. doi: 10.1016/j.parkreldis.2021.07.024

 

  1. Patel R, Stebbins G, Bernard B, Goldman J. Hippocampal and entorhinal cortex atrophy across the Parkinson’s disease cognitive impairment spectrum (S39.004). Neurology. 2017;88(16-Suppl):S39. doi: 10.1212/WNL.88.16-supplement.S39.004

 

  1. Frisoni GB, Laakso MP, Beltramello A, et al. Hippocampal and entorhinal cortex atrophy in frontotemporal dementia and Alzheimer’s disease. Neurology. 1999;52(1):91-91. doi: 10.1212/wnl.52.1.91

 

  1. Iizuka N, Masaoka Y, Kubota S, et al. Entorhinal cortex and parahippocampus volume reductions impact olfactory decline in aged subjects. Brain Behav. 2021;11(5):e02115. doi: 10.1002/brb3.2115

 

  1. Kubota S, Masaoka Y, Sugiyama H, et al. Hippocampus and parahippocampus volume reduction associated with impaired olfactory abilities in subjects without evidence of cognitive decline. Front Human Neurosci. 2020;14:556519. doi: 10.3389/fnhum.2020.556519

 

  1. Bitzenhofer SH, Westeinde EA, Zhang HXB, Isaacson JS. Rapid odor processing by layer 2 subcircuits in lateral entorhinal cortex. Elife. 2022;11:e75065. doi: 10.7554/eLife.75065

 

  1. Sun Y, Jin S, Lin X, et al. CA1-projecting subiculum neurons facilitate object-place learning. Nat Neurosci. 2019;22(11):1857-1870. doi: 10.1038/s41593-019-0496-y

 

  1. Chen YN, Kostka JK, Bitzenhofer SH, Hanganu-Opatz IL. Olfactory bulb activity shapes the development of entorhinal-hippocampal coupling and associated cognitive abilities. Curr Biol. 2023;33(20):4353-4366.e5. doi: 10.1016/j.cub.2023.08.072

 

  1. Donzuso G, Sciacca G, Rascunà C, et al. Structural MRI substrate of long-duration response to levodopa in Parkinson’s disease: An exploratory study. J Neurol. 2021;268:4258-4264. doi: 10.1007/s00415-021-10550-5

 

  1. Kaur K, Gill JS, Bansal PK, Deshmukh R. Neuroinflammation - a major cause for striatal dopaminergic degeneration in Parkinson’s disease. J Neurol Sci. 2017;381:308-314. doi: 10.1016/j.jns.2017.08.3251

 

  1. Vivekanantham S, Shah S, Dewji R, Dewji A, Khatri C, Ologunde R. Neuroinflammation in Parkinson’s disease: Role in neurodegeneration and tissue repair. Int J Neurosci. 2015;125(10):717-725. doi: 10.3109/00207454.2014.982795

 

  1. Araújo B, Caridade-Silva R, Soares-Guedes C, et al. Neuroinflammation and Parkinson’s disease-from neurodegeneration to therapeutic opportunities. Cells. 2022;11(18):2908. doi: 10.3390/cells11182908

 

  1. Ielo A, Bonanno L, Brunati C, et al. Structural and functional connectomics of the olfactory system in Parkinson’s disease: A systematic review. Parkinsonism Relat Disord. 2024;132:107230. doi: 10.1016/j.parkreldis.2024.107230

 

  1. Georgiopoulos C, Warntjes M, Dizdar N, et al. Olfactory impairment in Parkinson’s disease studied with diffusion tensor and magnetization transfer imaging. J Parkinsons Dis. 2017;7(2):301-311. doi: 10.3233/JPD-161060

 

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Advanced Neurology, Electronic ISSN: 2810-9619 Print ISSN: 3060-8589, Published by AccScience Publishing
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