| Summary: | Background: Parkinson's disease (PD) affects the integrity of the dopamine and serotonin system, and is characterized by a plethora of different symptoms, including cognitive impairments of which the pathophysiology is not yet fully elucidated. Objectives: Investigate the role of the integrity of the dopaminergic and serotonergic system in cognitive functioning in early-stage PD using Single Photon Emission Computed Tomography (SPECT) combined with the radiotracer 123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (123I-FP-CIT). Methods: We studied the association between cognitive functions and dopamine transporter (DAT) availability in the caudate nucleus and putamen – as a proxy for striatal dopaminergic integrity – and serotonin transporter (SERT) availability as a proxy for serotonergic integrity in the thalamus and hippocampus using bootstrapped multiple regression. One-hundred-and-twenty-nine (129) PD patients underwent a 123I-FP-CIT SPECT scan and a neuropsychological assessment. Results: We showed a positive association between DAT availability in the head of the caudate nucleus and the Stroop Color Word Task – card I (reading words; β = 0.32, P = 0.001) and a positive association between DAT availability in the anterior putamen and the Trail Making Test part A (connecting consecutively numbered circles; β = 0.25, P = 0.02). These associations remained after adjusting for motor symptom severity or volume of the region-of-interest and were most pronounced in medication-naïve PD patients. There were no associations between cognitive performance and SERT availability in the thalamus or hippocampus. Conclusions: We interpret these results as a role for striatal dopamine – and its PD-related decline – in aspects of processing speed.
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