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Decline in prefrontal catecholamine synthesis explains age-related changes in cognitive speed beyond regional grey matter atrophy

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

Abstract

Purpose

Age-related decline in cognitive speed has been associated with prefrontal dopamine D1 receptor availability, but the contribution of presynaptic dopamine and noradrenaline innervation to age-related changes in cognition is unknown.

Methods

In a group of 16 healthy participants aged 22–61 years, we used PET and the radioligand FDOPA to measure catecholamine synthesis capacity (K in app; millilitres per gram per minute) and the digit symbol substitution test to measure cognitive speed, a component of fluid IQ.

Results

Cognitive speed was associated with the magnitude of K in app in the prefrontal cortex (p < 0.0005). Both cognitive speed (p = 0.003) and FDOPA K in app (p < 0.0005) declined with age, both in a standard voxel-wise analysis and in a volume-of-interest analysis with partial volume correction, and the correlation between cognitive speed and K in app remained significant beyond the effects of age (p = 0.047). MR-based segmentation revealed that these age-related declines were not attributable to age-related alterations in grey matter density.

Conclusion

Our findings indicate that age-related changes in the capacity of the prefrontal cortex to synthesize catecholamines, irrespective of cortical atrophy, may underlie age-related decline in cognitive speed.

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Acknowledgments

We thank R. Lorenz, M. Keitel, A. Goldmann and B. Neumann for assistance with data acquisition; N. Fonyuy and E. Jaeschke for assistance with PET; and R. Michel and A. Gerhardt for radiochemical analysis. This study was supported by the German Science Foundation (DFG HE2597/4-3&7-3 and DFG Exc257), by the German Ministry for Education and Research (BMBF 01QG87164 and 01GS08195) and by a MaxNetAging award to M.A.R.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Campus Mitte, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Jan Kalbitzer, Lorenz Deserno, Florian Schlagenhauf, Anne Beck, Thomas Mell, Gerd Bahr, Andreas Heinz & Michael A. Rapp

  2. Department of Nuclear Medicine, University of Mainz, Mainz, Germany

    Hans-Georg Buchholz

  3. Department of Nuclear Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany

    Michail Plotkin & Ralph Buchert

  4. Japan Labour Health and Welfare Organization, Kanto Rosai Hospital, Kawasaki City, Kanagawa, Japan

    Yoshitaka Kumakura

  5. Department of Nuclear Medicine, Ludwig-Maximilian University, Munich, Germany

    Paul Cumming

  6. Cluster of Excellence NeuroCure, Charité – Universitätsmedizin Berlin, Berlin, Germany

    Andreas Heinz

  7. Mount Sinai School of Medicine, New York, NY, USA

    Michael A. Rapp

Authors
  1. Jan Kalbitzer
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  2. Lorenz Deserno
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  3. Florian Schlagenhauf
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  4. Anne Beck
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  5. Thomas Mell
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  6. Gerd Bahr
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  7. Hans-Georg Buchholz
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  8. Michail Plotkin
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  9. Ralph Buchert
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  10. Yoshitaka Kumakura
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  11. Paul Cumming
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  12. Andreas Heinz
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  13. Michael A. Rapp
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Corresponding author

Correspondence to Jan Kalbitzer.

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Kalbitzer, J., Deserno, L., Schlagenhauf, F. et al. Decline in prefrontal catecholamine synthesis explains age-related changes in cognitive speed beyond regional grey matter atrophy. Eur J Nucl Med Mol Imaging 39, 1462–1466 (2012). https://doi.org/10.1007/s00259-012-2162-4

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  • DOI: https://doi.org/10.1007/s00259-012-2162-4

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