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Olfactory dysfunction correlates with putaminal dopamine turnover in early de novo Parkinson’s disease

  • Neurology and Preclinical Neurological Studies - Original Article
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Abstract

Although olfactory dysfunction is one of the most well-established prodromal symptoms in Parkinson’s disease (PD), its correlation with clinical disease progression or dopaminergic dysfunction still remains unclear. We here evaluated the association of striatal dopamine metabolism and olfactory function in a homogenous cohort of 30 patients with early untreated de novo PD. Striatal dopamine metabolism was assessed by the extended 18Fluorodopa PET scanning protocol to measure 18Fluorodopa uptake (Kocc) and the effective dopamine distribution volume ratio (EDVR) as the inverse of dopamine turnover. Olfactory function was estimated by the “Sniffin’ Sticks” test including odor threshold (T), discrimination (D) and identification (I) assessment. We detected moderate correlations of the EDVR in the posterior putamen with the TDI composite score (r = 0.412; p = 0.024; Pearson’s correlation test) and the odor identification score (r = 0.444; p = 0.014). These correlations were confirmed by multivariate regression analyses using age, sex, symptom duration and disease severity as measured by UPDRSIII motor score as candidate covariates. No other associations were observed between olfaction measures and Kocc and EDVR in all striatal regions. Together, olfactory dysfunction in early PD is not correlated with striatal 18Fluorodopa uptake as a measure for dopaminergic degeneration, but with putaminal dopamine turnover as a marker for dopaminergic presynaptic compensatory processes in early PD. These results should be treated as hypothesis generating and require confirmation by larger multicenter studies.

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Acknowledgements

The authors are grateful to the patients and their relatives, and the teams of the Movement Disorders Outpatient Centre at Dresden University of Technology, the PET division of the Forschungszentrum Dresden-Rossendorf (FZD) and the Coordination Centre for Clinical Trials at the Technische Universität Dresden.

Funding

The original clinical trial was supported by an unrestricted grant from Pfizer Pharma GmbH, Berlin, Germany. The financial sponsors of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding authors had full access to all data in the study and had final responsibility for the decision to submit for publication.

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Authors and Affiliations

  1. Department of Neurology, University of Rostock, Gehlsheimer Strasse 20, 18147, Rostock, Germany

    Matthias Löhle & Alexander Storch

  2. German Centre for Neurodegenerative Diseases (DZNE) Rostock, 18147, Rostock, Germany

    Matthias Löhle & Alexander Storch

  3. Department of Neurology, Elblandklinikum Meißen, Meissen, Germany

    Martin Wolz

  4. Department of Nuclear Medicine, Technische Universität Dresden, 01307, Dresden, Germany

    Bettina Beuthien-Baumann, Liane Oehme & Jörg Kotzerke

  5. Positron Emission Tomography Division, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany

    Bettina Beuthien-Baumann & Jörg van den Hoff

  6. Department of Neurology, Technische Universität Dresden, 01307, Dresden, Germany

    Heinz Reichmann

Authors
  1. Matthias Löhle
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  2. Martin Wolz
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  3. Bettina Beuthien-Baumann
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  4. Liane Oehme
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  5. Jörg van den Hoff
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  6. Jörg Kotzerke
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  7. Heinz Reichmann
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  8. Alexander Storch
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Contributions

Dr. ML recruited patients, collected clinical data, analysed and interpreted the data, and critically revised the manuscript. Dr. MW recruited patients, collected clinical data, analysed and interpreted the data, and critically revised the manuscript. Dr. BB-B, Dr. LO and Dr. JH collected and analysed PET data and critically revised the manuscript. Dr. JK contributed to the study design, organized funding, analysed PET data and critically revised the manuscript. Dr. HR contributed to the study design, organized funding and critically revised the manuscript. Dr. AS contributed to the study design, organized funding, recruited patients, collected clinical data, analysed and interpreted the data, and wrote the manuscript.

Corresponding authors

Correspondence to Matthias Löhle or Alexander Storch.

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Conflict of interest

M. Löhle has received has received honoraria for presentations from Bayer Healthcare and UCB Pharma. Dr. Wolz reports personal fees from Boehringer Ingelheim, Zambon, Valeant, Desitin, TEVA, UCB Pharma, Abbvie, Licher, and Daiichi Sankyo, outside the submitted work. B. Beuthien-Baumann has received honoraria for presentations/lectures from BRACCO and Roche Pharma AG, Basel, Switzerland. Dr. Oehme reports no disclosures. Dr. van den Hoff reports no disclosures. Dr. Kotzerke reports no disclosures. H. Reichmann was acting on advisory boards and gave lectures and received research grants from Bayer Health Care, Boehringer/Ingelheim, Cephalon, Desitin, GlaxoSmithKline, Merck-Serono, Novartis, Orion, Pfizer, Solvay, TEVA/Lundbeck, UCB Pharma, and Valeant. Dr. Storch has received funding from the Deutsche Forschungsgemeinschaft (DFG) and the Helmholtz Association. He received unrestricted research grants from GKC Melbourne, Pfizer, and TEVA Pharma, honoraria for presentations/lectures/consultancies or advisory boards from AbbVie, Bayer Healthcare, Bial, GKC, Grünenthal, UCB, Zambon, Ca, AbbVie, TEVA, Lundbeck, and UCB Pharma, outside the submitted work. He has served on the editorial boards of Stem Cells and Stem Cells International.

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Löhle, M., Wolz, M., Beuthien-Baumann, B. et al. Olfactory dysfunction correlates with putaminal dopamine turnover in early de novo Parkinson’s disease. J Neural Transm 127, 9–16 (2020). https://doi.org/10.1007/s00702-019-02122-9

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  • DOI: https://doi.org/10.1007/s00702-019-02122-9

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