TY - JOUR
T1 - Rapid eye movement sleep behavior disorder: A proof-of-concept neuroprotection study for prodromal synucleinopathies
AU - Arnaldi, Dario
AU - Famà, Francesco
AU - Girtler, Nicola
AU - Brugnolo, Andrea
AU - Pardini, Matteo
AU - Mattioli, Pietro
AU - Meli, Riccardo
AU - Massa, Federico
AU - Orso, Beatrice
AU - Sormani, Maria Pia
AU - Donegani, Maria Isabella
AU - Bauckneht, Matteo
AU - Morbelli, Silvia
AU - Nobili, Flavio
N1 - Funding Information:
This work was developed within the framework of the DINOGMI Department of Excellence of MIUR 2018‐2022 (legge 232 del 2016). This work was supported by a grant from the Italian Ministry of Health–Italian Neuroscience Network (RIN).
Funding Information:
This research did not receive any specific grant from funding agencies in the public, commercial, or not‐for‐profit sectors. Dario Arnaldi received fees from Fidia for lectures and board participation. Francesco Famà, Nicola Girtler, Andrea Brugnolo, Pietro Mattioli, Riccardo Meli, Federico Massa, Beatrice Orso, Maria Pia Sormani, Maria Isabella Donegani, and Matteo Bauckneht report no disclosures. Matteo Pardini receives research support from Novartis and Nutricia and received fees from Novartis, Merck, and Biogen. Silvia Morbelli received speaking honoraria from G.E. Healthcare. Flavio Nobili received fees from BIAL for consultation, from G.E. Healthcare for teaching lectures, and from Roche for board participation.
Publisher Copyright:
© 2020 European Academy of Neurology
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - Background and purpose: To explore the feasibility of a neuroprotection trial in prodromal synucleinopathy, using idiopathic rapid eye movement sleep behavior disorder (iRBD) as the target population and 123I-FP-CIT-SPECT as a biomarker of disease progression. Methods: Consecutive iRBD patients were randomly assigned to a treatment arm receiving selegiline and symptomatic rapid eye movement sleep behavior disorder treatment, or to a control arm receiving symptomatic treatment only. Selegiline was chosen because of a demonstrated neuroprotection effect in animal models. Patients underwent 123I-FP-CIT-SPECT at baseline and after 30 months on average. The clinical outcome was the emergence of parkinsonism and/or dementia. A repeated-measures general linear model (GLM) was applied using group (control and treatment) as ”between” factor, and both time (baseline and follow-up) and regions (123I-FP-CIT-SPECT putamen and caudate uptake) as the ”within” factors, adjusting for age. Results: Thirty iRBD patients completed the study (68.2 ± 6.9 years; 29 males; 21% dropout rate), 13 in the treatment arm, and 17 in the control arm. At follow-up (29.8 ± 9.0 months), three patients in the control arm developed dementia and one parkinsonism, whereas two patients in the treatment arm developed parkinsonism. Both putamen and caudate uptake decreased over time in the control arm. In the treatment arm, only the putamen uptake decreased over time, whereas caudate uptake remained stable. GLM analysis demonstrated an effect of treatment on the 123I-FP-CIT-SPECT uptake change, with a significant interaction between the effect of group, time, and regions (p = 0.004). Conclusions: A 30-months neuroprotection study for prodromal synucleinopathy is feasible, using iRBD as the target population and 123I-FP-CIT-SPECT as a biomarker of disease progression.
AB - Background and purpose: To explore the feasibility of a neuroprotection trial in prodromal synucleinopathy, using idiopathic rapid eye movement sleep behavior disorder (iRBD) as the target population and 123I-FP-CIT-SPECT as a biomarker of disease progression. Methods: Consecutive iRBD patients were randomly assigned to a treatment arm receiving selegiline and symptomatic rapid eye movement sleep behavior disorder treatment, or to a control arm receiving symptomatic treatment only. Selegiline was chosen because of a demonstrated neuroprotection effect in animal models. Patients underwent 123I-FP-CIT-SPECT at baseline and after 30 months on average. The clinical outcome was the emergence of parkinsonism and/or dementia. A repeated-measures general linear model (GLM) was applied using group (control and treatment) as ”between” factor, and both time (baseline and follow-up) and regions (123I-FP-CIT-SPECT putamen and caudate uptake) as the ”within” factors, adjusting for age. Results: Thirty iRBD patients completed the study (68.2 ± 6.9 years; 29 males; 21% dropout rate), 13 in the treatment arm, and 17 in the control arm. At follow-up (29.8 ± 9.0 months), three patients in the control arm developed dementia and one parkinsonism, whereas two patients in the treatment arm developed parkinsonism. Both putamen and caudate uptake decreased over time in the control arm. In the treatment arm, only the putamen uptake decreased over time, whereas caudate uptake remained stable. GLM analysis demonstrated an effect of treatment on the 123I-FP-CIT-SPECT uptake change, with a significant interaction between the effect of group, time, and regions (p = 0.004). Conclusions: A 30-months neuroprotection study for prodromal synucleinopathy is feasible, using iRBD as the target population and 123I-FP-CIT-SPECT as a biomarker of disease progression.
KW - dementia with Lewy bodies
KW - Parkinson's disease
KW - REM sleep behavior disorder
KW - SPECT
KW - synucleinopathy
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U2 - 10.1111/ene.14664
DO - 10.1111/ene.14664
M3 - Article
C2 - 33275819
AN - SCOPUS:85099499269
JO - European Journal of Neurology
JF - European Journal of Neurology
SN - 1351-5101
ER -