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Anterior cingulate dopamine turnover and behavior change in Parkinson’s disease

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Abstract

Subtle cognitive and behavioral changes are common in early Parkinson’s disease. The cause of these symptoms is probably multifactorial but may in part be related to extra-striatal dopamine levels. 6-[18 F]-Fluoro-L-dopa (FDOPA) positron emission tomography has been widely used to quantify dopamine metabolism in the brain; the most frequently measured kinetic parameter is the tissue uptake rate constant, Ki. However, estimates of dopamine turnover, which also account for the small rate of FDOPA loss from areas of specific trapping, may be more sensitive than Ki for early disease-related changes in dopamine biosynthesis. The purpose of the present study was to compare effective distribution volume ratio (eDVR), a metric for dopamine turnover, to cognitive and behavioral measures in Parkinson’s patients. We chose to focus the investigation on anterior cingulate cortex, which shows highest FDOPA uptake within frontal regions and has known roles in executive function. Fifteen non-demented early-stage PD patients were pretreated with carbidopa and tolcapone, a central catechol-O-methyl transferase (COMT) inhibitor, and then underwent extended imaging with FDOPA PET. Anterior cingulate eDVR was compared with composite scores for language, memory, and executive function measured by neuropsychological testing, and behavior change measured using two informant-based questionnaires, the Cambridge Behavioral Inventory and the Behavior Rating Inventory of Executive Function-Adult Version. Lower mean eDVR (thus higher dopamine turnover) in anterior cingulate cortex was related to lower (more impaired) behavior scores. We conclude that subtle changes in anterior cingulate dopamine metabolism may contribute to dysexecutive behaviors in Parkinson’s disease.

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Acknowledgments

This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Science Research and Development Service. It was also funded by the University of Wisconsin Institute for Clinical and Translational Research, through a National Institutes of Health Clinical and Translational Science Award, [grant number 1UL1RR025011]. This work was supported with use of facilities at the William S. Middleton Memorial Veterans Hospital Geriatric Research Education and Clinical Center and the Waisman Laboratory for Brain Imaging and Behavior, Madison, WI, USA.

Disclosures

Authors Gallagher, Bell, Palotti, Oh, Christian, Okonkwo, Sojkova, Buyan-Dent, Nickles, Harding, Stone, Johnson, and Holden declare no conflicts of interest.

Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of this investigation. Informed consent was obtained from all study participants.

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Authors and Affiliations

  1. William S. Middleton Veterans Hospital, Madison, WI, USA

    Catherine L. Gallagher, Matthew Palotti, Jitka Sojkova & Sterling C. Johnson

  2. Department of Neurology, University of Wisconsin School of Medicine and Public Health, 7211 MFCB, 1685 Highland Ave., Madison, WI, 53705-2281, USA

    Catherine L. Gallagher, Brian Bell, Matthew Palotti, Jitka Sojkova & Laura Buyan-Dent

  3. Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Catherine L. Gallagher, Jen Oh, Ozioma Okonkwo, Jitka Sojkova, Sandra J. Harding & Sterling C. Johnson

  4. University of Wisconsin Department of Medical Physics, Madison, WI, USA

    Bradley T. Christian, Robert J. Nickles & James E. Holden

  5. Waisman Laboratory for Brain Imaging and Behavior, Madison, WI, USA

    Bradley T. Christian

  6. Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Ozioma Okonkwo, Sandra J. Harding, Charles K. Stone & Sterling C. Johnson

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  1. Catherine L. Gallagher
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  2. Brian Bell
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  3. Matthew Palotti
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  4. Jen Oh
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  13. James E. Holden
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Correspondence to Catherine L. Gallagher.

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Gallagher, C.L., Bell, B., Palotti, M. et al. Anterior cingulate dopamine turnover and behavior change in Parkinson’s disease. Brain Imaging and Behavior 9, 821–827 (2015). https://doi.org/10.1007/s11682-014-9338-4

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