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


Gallagher, CL, Bell B, Palotti M, Oh J, Christian BT, Okonkwo OC, Sjokova J, Buyan-Dent L, Nickles R, Harding S, Stone C, Johnson SC, Holden J

Brain Imaging and Behavior. 2015 Dec;9(4):821-7.

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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