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Striatal metabolism and psychomotor speed as predictors of motor onset in Huntington’s disease

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Abstract

The clinical diagnosis of Huntington’s disease (HD) is based on the motor symptoms, although these can be preceded by cognitive and behavioral changes. Biomarker studies have shown that structural imaging modalities are useful biomarkers of HD onset, while functional imaging measures have been studied less often for this purpose. Our aim was to investigate the combined value of 18-fluorodesoxyglucose (FDG)–PET and cognitive measures as biomarkers of HD onset. Twenty-two premanifest mutation carriers of HD (PMCs) and 11 healthy controls were assessed twice with FDG–PET scan, neurological and neuropsychological assessments over a 2-year interval. Seventeen PMCs had an additional third neurological evaluation, 10 years after baseline. Disease load was defined as the probability of motor onset within 5 years. Metabolism in putamen, caudate and pallidum of PMCs was significantly lower than that of controls, at both assessments. Almost half of the PMCs had converted to manifest HD 10 years later and all converters had low average or abnormal putaminal metabolism at 2 year follow-up. In contrast, all PMCs with normal putaminal metabolism at 2 year follow-up remained premanifest during the following 8 years. Furthermore, glucose metabolism of putamen explained a substantial part of the variance in disease load. A composite score of psychomotor tests contributed significantly to the prediction model as well, while cognitive performance was comparable for PMCs and controls. We conclude that in future clinical trials a combination of psychomotor tests and putaminal glucose metabolism may be used to identify PMCs close to motor onset of HD.

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Acknowledgments

The authors thank all participants for their effort and A.T.M. Willemsen for his help with the FDG–PET data analysis. This work was financed by the Prinses Beatrix Fonds, Project No. 99-0209.

Ethical standards

This study was approved by the local ethics committee and the research was conducted in compliance with institutional guidelines. All subjects gave their written informed consent.

Conflicts of interest

The research was conducted in compliance with institutional guidelines. There are no potential conflicts of interest in this study. This manuscript, or parts of it, has not been previously published elsewhere nor has it been submitted simultaneously for publication elsewhere.

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Author notes

  1. Joost C. H. van Oostrom

    Present address: Department of Neurology, Rijnstate Hospital, Arnhem, The Netherlands

  2. Caroline K. Jurgens & Marie-Noëlle W. Witjes-Ané

    Present address: Department of Psychology, Bronovo Hospital, The Hague, The Netherlands

Authors and Affiliations

  1. Department of Neurology, University Medical Center Groningen, AB50, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands

    Meike Herben-Dekker, Joost C. H. van Oostrom, Hubertus P. H. Kremer & Klaus L. Leenders

  2. Department of Clinical and Experimental Neuropsychology, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands

    Jacoba M. Spikman

  3. Department of Neurology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands

    Raymund A. C. Roos, Caroline K. Jurgens & Marie-Noëlle W. Witjes-Ané

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  1. Meike Herben-Dekker
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Correspondence to Meike Herben-Dekker.

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Herben-Dekker, M., van Oostrom, J.C.H., Roos, R.A.C. et al. Striatal metabolism and psychomotor speed as predictors of motor onset in Huntington’s disease. J Neurol 261, 1387–1397 (2014). https://doi.org/10.1007/s00415-014-7350-7

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  • DOI: https://doi.org/10.1007/s00415-014-7350-7

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