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Association of olfaction dysfunction with brain microstructure in prodromal Parkinson disease

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Abstract

Objective

Although olfaction dysfunction is now considered as an established clinical marker of prodromal Parkinson disease (PD), little is known about the neural underpinnings of olfaction dysfunction in the prodromal phase of PD. The aim of this study was to examine the microstructural association of olfaction in prodromal PD compared to early stage drug-naïve PD patients.

Methods

Diffusion MRI connectometry was conducted on 18 early PD and 17 prodromal PD patients to investigate the differences in group in terms of altered connectivity, i.e., integrity of white matter tracts, and subsequently to study the correlation of University of Pennsylvania Smell Identification Test (UPSIT) score to white matter integrity in each group using a multiple regression model considering age, sex, RBD, and MoCA, as covariates.

Results

Individuals with prodromal PD had significantly higher quantitative anisotropy (QA) comparing with PD patients in bilateral middle cerebellar peduncles and right arcuate fasciculus. Multiple regression analysis in prodromal PD demonstrated positive association between UPSIT score and connectivity in left and right subgenual cingulum, right inferior fronto-occipital fasciculus, left corticospinal tract, left parietopontine, left corticothalamic tract, and the body and the splenium of corpus callosum.

Conclusion

These results indicate that PD and prodromal PD patients, which were matched for sex, UPSIT, and MoCA scores, have different white matter fiber architecture. Thus, it is postulated that olfaction dysfunction in prodromal and early clinical phases of PD may involve distinct pathogenesis. Increased network connectivity in prodromal and early PD may suggest the neural compensation.

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Acknowledgments

We thank Christian Beckmann and Simon Eickhoff for their advice on data analysis. Data used in this article were obtained from the Parkinsons Progression Markers Initiative (PPMI) database (www.ppmi-info.org/data). For up-to-date information on the study, visit www.ppmi-info.org.

Funding

This dataset of this work was funded by grants from the Michael J Fox Foundation for Parkinson’s Research, the W Garfield Weston Foundation, and the Alzheimer’s Association, the Canadian Institutes for Health Research, and the Natural Sciences and Engineering Research Council of Canada. PPMI is sponsored and partially funded by the Michael J Fox Foundation for Parkinsons Research and funding partners, including AbbVie, Avid Radiopharmaceuticals, Biogen, Bristol-Myers Squibb, Covance, GE Healthcare, Genentech, GlaxoSmithKline (GSK), Eli Lilly and Company, Lundbeck, Merck, Meso Scale Discovery (MSD), Pfizer, Piramal Imaging, Roche, Servier, and UCB (www.ppmi-info.org/fundingpartners).

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  1. Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Hossein Sanjari Moghaddam, Mahsa Dolatshahi, Elaheh Salardini & Mohammad Hadi Aarabi

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  1. Hossein Sanjari Moghaddam
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  2. Mahsa Dolatshahi
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Contributions

H.S.M, M.H.A. contributed to the conception and design of the study; M.H.A. contributed to data collection and analysis; and H.S.M, M.D, and E.S.D contributed to writing and revising the manuscript.

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Correspondence to Mohammad Hadi Aarabi.

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All procedures performed here, including human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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The authors declare that they have no conflict of interest.

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Sanjari Moghaddam, H., Dolatshahi, M., Salardini, E. et al. Association of olfaction dysfunction with brain microstructure in prodromal Parkinson disease. Neurol Sci 40, 283–291 (2019). https://doi.org/10.1007/s10072-018-3629-2

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