Abstract
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. 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). 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. 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. We interpret these results as a role for striatal dopamine - and its PD-related decline - in aspects of processing speed.
Highlights
Cognitive impairments are common in Parkinson's disease (PD), with cognitive impairment already present in up to twenty-five percent of patients around the time of diagnosis (Muslimovic et al, 2005; Weintraub et al, 2015)
In this study we investigated the association between striatal and extrastriatal 123I-FP-CIT binding and cognitive performance in a large sample of early-stage PD patients
Using bootstrapped multiple regression analysis our main finding was that age-adjusted 123I-FP-CIT binding in the head of the caudate nucleus and anterior putamen were positively associated with cognitive performance on the Stroop Color Word Test (SCWT) card I and Trail Making Test (TMT) card A, respectively
Summary
Cognitive impairments are common in Parkinson's disease (PD), with cognitive impairment already present in up to twenty-five percent of patients around the time of diagnosis (Muslimovic et al, 2005; Weintraub et al, 2015). The integrity of dopaminergic projections can be approximated in vivo by measuring the availability of striatal presynaptic dopamine transporters (DAT) using radiotracers, such as 123I-N-ω-fluoropropyl2β-carbomethoxy-3β-(4-iodophenyl)nortropane (123I-FP-CIT) in combination with single photon emission computed tomography (SPECT). Using such radiotracers, studies have shown lower striatal DAT binding, indicative of more dopamine denervation (Scherfler et al, 2007), in PD patients with cognitive impairments compared with those without (Chung et al, 2018; Ekman et al, 2012; Schrag et al, 2017). 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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