Background: Neuropathological data and nuclear medicine imaging show extensive serotonergic impairment in Parkinson’s disease (PD). We undertook a case-controlled analysis of 123I-FP-CIT SPECT images to measure extrastriatal serotonergic transporters (SERT) in PD using the Parkinson’s Progression Markers Initiative (PPMI) cohort. Methods: We included all PD (n=154) and Control subjects (n=62) with available 123I-FP-CIT SPECT imaging and high-resolution T1-weighted MRI for coregistration (PD: mean age 61.6 years, 62% male, disease duration 26 months, MDS-UPDRS III score 22). 123I-FP-CIT SPECT images were processed with PETPVE12 using an exploratory voxel-wise analysis including partial-volume effect correction. Linear regressions were performed in the PD group to assess correlations between region of interest 123I-FP-CIT uptake and clinical motor and non-motor impairment.Results: Compared to Controls, PD exhibited an uptake reduction in bilateral caudate nucleus, putamen, insula, amygdala and right pallidum (family-wise error (FWE)-corrected p<0.05). While lower putaminal uptake on the contralateral side to clinically more affected side was associated with higher MDS-UPDRS III score (p=0.022), we found a trend association between higher geriatric depression scale and lower pallidum uptake (p=0.09). Higher SCOPA-AUT gastrointestinal subscore was associated with lower uptake in mean putamen and caudate nucleus (p=0.01 to 0.03), whereas urological subscore was inversely correlated with mean caudate nucleus, putamen, and pallidum uptake (p=0.002 to 0.03). REM sleep behaviour disorder screening questionnaire was associated with lower 123I-FP-CIT binding in caudate nucleus, putamen and pallidum (all p<0.05). No significant association was found for Montreal Cognitive Assessment (all p>0.45) or excessive daytime sleepiness (all p > 0.29). Conclusions: In addition to the well-established striatal deficit, this study provides evidence of a major extrastriatal 123I-FP-CIT impairment, and therefore of an altered serotonergic transmission in early PD.

Background: Neuropathological data and nuclear medicine imaging show extensive serotonergic impairment in Parkinson’s disease (PD). We aimed at undertaking a case-controlled analysis of 123I-FP-CIT SPECT images to measure extrastriatal serotonergic transporters (SERT) in PD using the Parkinson’s Progression Markers Initiative (PPMI) cohort. Methods: We included all PD (n=154) and Control subjects (n=62) with available 123I-FP-CIT SPECT imaging and high-resolution T1-weighted MRI for coregistration (PD: mean age 61.6 years, 62% male, disease duration 26 months, MDS-UPDRS III score 22). 123I-FP-CIT SPECT images were processed with PETPVE12 using an exploratory voxel-wise analysis including partial-volume effect correction. Linear regressions were performed in the PD group to assess correlations between region of interest 123I-FP-CIT uptake and clinical motor and non-motor impairment.Results: Compared to Controls, PD exhibited an uptake reduction in bilateral caudate nucleus, putamen, insula, amygdala and right pallidum (family-wise error (FWE)-corrected p<0.05). While lower contralateral putaminal uptake was associated with higher MDS-UPDRS III score (p=0.022), we found a trend association between higher geriatric depression scale and lower pallidum uptake (p=0.09). Higher SCOPA-AUT gastrointestinal subscore was associated with lower uptake in mean putamen and caudate nucleus (p=0.01 to 0.03), whereas urological subscore was inversely correlated with mean caudate nucleus, putamen, and pallidum uptake (p=0.002 to 0.03). No significant association was found for Montreal Cognitive Assessment (all p>0.45). Conclusions: In addition to the well-established striatal deficit, this study provides evidence of a major extrastriatal 123I-FP-CIT impairment, and therefore of an altered serotonergic transmission in early PD.