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Hypermetabolism in the cerebellum and brainstem and cortical hypometabolism are independently associated with cognitive impairment in Parkinson’s disease

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Cognitive impairment (CI) in Parkinson’s disease (PD) is associated with a widespread reduction in cortical glucose metabolism and relative increases in the cerebellum and brainstem as measured using 18F-fluorodesoxyglucose (FDG) PET. We separately analysed CI-related hypermetabolism and hypometabolism in comparison with neuropsychological test performance and investigated whether increased FDG uptake is a true feature of the disease or a normalization effect.

Methods

The study included 29 subjects (12 patients with PD, 10 patients with PD dementia and 7 healthy controls") who underwent FDG PET and comprehensive neuropsychological testing. Test performance across various cognitive domains was summarized in a cognitive staging score. Metabolic indices reflecting associated changes in regional cerebral glucose metabolism (rCGM) were calculated: index(−) for CI-related hypometabolism, and index(+) for CI-related hypermetabolism. We tested whether index(+) offered additional value in predicting the severity of CI in multiple regression analysis.

Results

At higher stages of CI, increased rCGM was found in the posterior cerebellar vermis and pons, associated with impaired attention, executive function and memory. Reduced rCGM was found in various cortical regions in agreement with the literature. In multiple regression analysis, both indices independently predicted the severity of CI with a whole-model R2 of 0.68 (index(−), p = 0.0006; index(+), p = 0.013), confirmed by alternative analyses combining different reference tissues in the multiple regression.

Conclusion

We found CI-related hypermetabolism in cerebellar regions that are known to be involved in several cognitive functions and in the pons. These alterations may represent compensatory activation of cognitive networks including cerebropontocerebellar tracts.

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Acknowledgments

We acknowledge the funding received from the European Community’s Seventh Framework Programme.

Funding

The research leading to these results received funding from the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 603646 (MultISyn).

Author information

Author notes

  1. Matthias Reimold and Inga Liepelt-Scarfone contributed equally to this work.

Authors and Affiliations

  1. German Center of Neurodegenerative Diseases, Eberhard Karls University, Tuebingen, Germany

    Dominik Blum, Andrea Pilotto & Inga Liepelt-Scarfone

  2. Hertie-Institute for Clinical Brain Research, Eberhard Karls University, Tuebingen, Germany

    Dominik Blum, Andrea Pilotto, Daniela Berg & Inga Liepelt-Scarfone

  3. Department of Nuclear Medicine and Clinical Molecular Imaging, Eberhard Karls University, Otfried-Müller-Str. 14, 72076, Tuebingen, Germany

    Dominik Blum, Christian la Fougère & Matthias Reimold

  4. Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy

    Andrea Pilotto

  5. Department of Neurology, Christian-Albrechts-University, Kiel, Germany

    Walter Maetzler & Daniela Berg

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  1. Dominik Blum
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Corresponding author

Correspondence to Matthias Reimold.

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Ethical approval

All procedures performed in this study were in accordance with the principles of the 1964 Declaration of Helsinki and its later amendments and were approved by the local ethics committee.

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

Electronic supplementary material

ESM 1

Neuropsychological test battery: descriptive statistics for the four cognitive staging groups and results from correlation analysis (voxelwise multiple regression with two independent variables, i.e. the respective neuropsychological score and, as nuisance variable, UPDRSIII). CI = cognitive impairment (DOCX 25 kb)

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Blum, D., la Fougère, C., Pilotto, A. et al. Hypermetabolism in the cerebellum and brainstem and cortical hypometabolism are independently associated with cognitive impairment in Parkinson’s disease. Eur J Nucl Med Mol Imaging 45, 2387–2395 (2018). https://doi.org/10.1007/s00259-018-4085-1

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  • DOI: https://doi.org/10.1007/s00259-018-4085-1

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