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Rapid eye movement sleep behavior disorder: A proof‐of‐concept neuroprotection study for prodromal synucleinopathies
Author(s) -
Arnaldi Dario,
Famà Francesco,
Girtler Nicola,
Brugnolo Andrea,
Pardini Matteo,
Mattioli Pietro,
Meli Riccardo,
Massa Federico,
Orso Beatrice,
Sormani Maria Pia,
Donegani Maria Isabella,
Bauckneht Matteo,
Morbelli Silvia,
Nobili Flavio
Publication year - 2021
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.14664
Subject(s) - medicine , parkinsonism , putamen , selegiline , rapid eye movement sleep , dementia with lewy bodies , synucleinopathies , rem sleep behavior disorder , parkinson's disease , dementia , caudate nucleus , population , neuroprotection , disease , eye movement , ophthalmology , alpha synuclein , environmental health
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 123 I‐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 123 I‐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 ( 123 I‐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 123 I‐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 123 I‐FP‐CIT‐SPECT as a biomarker of disease progression.