title: Anterior cingulate dopamine turnover and behavior change in Parkinson's disease.
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.
authors.affiliation: William S. Middleton Veterans Hospital, Madison, WI, USA. gallagher@neurology.wisc.edu.|Department of Neurology, University of Wisconsin School of Medicine and Public Health, 7211 MFCB, 1685 Highland Ave., Madison, WI, 53705-2281, USA. gallagher@neurology.wisc.edu.|Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. gallagher@neurology.wisc.edu.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Gallagher
authors.affiliation: Department of Neurology, University of Wisconsin School of Medicine and Public Health, 7211 MFCB, 1685 Highland Ave., Madison, WI, 53705-2281, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Bell
authors.affiliation: William S. Middleton Veterans Hospital, Madison, WI, USA.|Department of Neurology, University of Wisconsin School of Medicine and Public Health, 7211 MFCB, 1685 Highland Ave., Madison, WI, 53705-2281, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Palotti
authors.affiliation: Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Jen
authors.initials: J
authors.lastname: Oh
authors.affiliation: University of Wisconsin Department of Medical Physics, Madison, WI, USA.|Waisman Laboratory for Brain Imaging and Behavior, Madison, WI, USA.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Christian
authors.affiliation: Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.|Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Ozioma
authors.initials: O
authors.lastname: Okonkwo
authors.affiliation: William S. Middleton Veterans Hospital, Madison, WI, USA.|Department of Neurology, University of Wisconsin School of Medicine and Public Health, 7211 MFCB, 1685 Highland Ave., Madison, WI, 53705-2281, USA.|Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Jitka
authors.initials: J
authors.lastname: Sojkova
authors.affiliation: Department of Neurology, University of Wisconsin School of Medicine and Public Health, 7211 MFCB, 1685 Highland Ave., Madison, WI, 53705-2281, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Buyan-Dent
authors.affiliation: University of Wisconsin Department of Medical Physics, Madison, WI, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Nickles
authors.affiliation: Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.|Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Harding
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Charles K
authors.initials: CK
authors.lastname: Stone
authors.affiliation: William S. Middleton Veterans Hospital, Madison, WI, USA.|Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.|Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Sterling C
authors.initials: SC
authors.lastname: Johnson
authors.affiliation: University of Wisconsin Department of Medical Physics, Madison, WI, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Holden
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000494:pharmacology; D001577:Benzophenones / Q000494:pharmacology; D002230:Carbidopa / Q000494:pharmacology; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors / Q000494:pharmacology; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism*; D005260:Female; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009596:Nitrophenols / Q000494:pharmacology; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D000077867:Tolcapone
chemical_list: D000978:Antiparkinson Agents; D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D009596:Nitrophenols; D019275:Radiopharmaceuticals; C029253:6-fluorodopamine; D000077867:Tolcapone; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; D002230:Carbidopa; D004298:Dopamine
keywords: Adult; Aged; Brain mapping; Cerebral cortex/metabolism/radionuclide imaging; Dihydroxyphenylalanine/*analogs & derivatives/drug effects/pharmacokinetics; Dopamine agents/*diagnostic use/pharmacokinetics; Humans; Parkinson disease/*physiopathology/*radionuclide imaging; Positron emission tomography; Research support/U.S. Gov’t/P.H.S.