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Extrastriatal 123I-FP-CIT SPECT impairment in Parkinson's disease - the PPMI cohort.

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Garibotto, Valentina 
Burkhard, Pierre R 


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.



Dopamine, Parkinson’s disease, SPECT, Serotonin, Adult, Aged, Brain, Case-Control Studies, Cohort Studies, Disease Progression, Female, Humans, Image Interpretation, Computer-Assisted, Iodine Radioisotopes, Male, Middle Aged, Parkinson Disease, Serotonin Plasma Membrane Transport Proteins, Tomography, Emission-Computed, Single-Photon, Tropanes

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BMC Neurol

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Springer Science and Business Media LLC