Abstract
BackgroundNeuropathological 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.MethodsWe 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.ResultsCompared 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).ConclusionsIn 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.
Highlights
Neuropathological data and nuclear medicine imaging show extensive serotonergic impairment in Parkinson’s disease (PD)
Parkinson’s disease (PD) and Progressive Supranuclear Palsy (PSP) [4,5,6]. 123I-FP-CIT serotonergic transporters (SERT) concentration has been shown to be higher in females and to decline with age [7], and reduced uptake has been observed for PD in frontal areas, thalamus, amygdala and insula [8, 9], confirming 11C-DASB positron emission tomography (PET) findings
We included all subjects who had both 123I-FP-CIT single photon emission computed tomography (SPECT) imaging and high-resolution 3 T T1-weighted magnetization-prepared rapid gradient echo (MPRAGE) MRI performed within 3 months
Summary
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. Using the Parkinson’s Progression Markers Initiative (PPMI) database [10], we here propose a case-controlled extrastriatal 123I-FP-CIT assessment of early PD subjects. We performed correlation analyses of striatal and extrastriatal significant regions of interest (ROI) uptake with clinical motor and non-motor scales, i.e. Movement Disorders Society (MDS)-Unified Parkinson’s Disease Rating Scale (UPDRS) part III at baseline and at 1year follow-up [11], Geriatric Depression Scale (GDS) [12], Montreal Cognitive Assessment (MoCA) [13], SCale for Outcome in PArkinson’s disease – AUTonomic dysfunction (SCOPA-AUT) [14], Epworth Sleepiness Scale (ESS) [15] and REM-sleep behaviour screening questionnaire (RBDSQ) [16]
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