Rapid eye movement sleep behavior disorder: A proof-of-concept neuroprotection study for prodromal synucleinopathies

Dario Arnaldi, Francesco Famà, Nicola Girtler, Andrea Brugnolo, Matteo Pardini, Pietro Mattioli, Riccardo Meli, Federico Massa, Beatrice Orso, Maria Pia Sormani, Maria Isabella Donegani, Matteo Bauckneht, Silvia Morbelli, Flavio Nobili

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
JournalEuropean Journal of Neurology
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • dementia with Lewy bodies
  • Parkinson's disease
  • REM sleep behavior disorder
  • SPECT
  • synucleinopathy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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