期刊
BMC NEUROLOGY
卷 20, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12883-020-01777-2
关键词
Parkinson's disease; Dopamine; Serotonin; SPECT
资金
- Michael J. Fox Foundation for Parkinson's Research
- Abbvie
- Allergan
- Amathus
- Avid
- Biogen
- Biolegend
- Bristol-Myers-Squibb
- Celgene
- Denali
- GE Healthcare
- Genentech
- Glaxo-Smith-Kline
- Handl therapeutics
- Insitro
- Janssen Neuroscience
- Lilly
- Lundbeck
- Merck
- Meso Scale Discovery
- Pfizer
- Piramal
- Prevail
- Roche
- Sanofi Genzyme
- Servier
- Takeda
- Teva
- UCB
- Verily
- Voyager therapeutics
Background Neuropathological data and nuclear medicine imaging show extensive serotonergic impairment in Parkinson's disease (PD). We undertook a case-controlled analysis of I-123-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 I-123-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). I-123-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 I-123-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 I-123-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 I-123-FP-CIT impairment, and therefore of an altered serotonergic transmission in early PD.
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