Aline Delva1, Seyed-Mohammad Fereshtehnejad2, Chun William Yao3, Amelie Pelletier4, Jacques Montplaisir5, Jean-François Gagnon6, Ronald Postuma4
1Montreal Neurological Institute, 2University of Toronto, 3Université de Montréal, 4Montreal General Hospital, 5Université de Montreal, 6UQAM
Objective:
To assess clinical features and changes in idiopathic REM-sleep behavior disorder (iRBD) the decade before clinical diagnosis of a manifest neurodegenerative disorder.
Background:
iRBD is a prodromal marker of underlying synucleinopathy in the brain. Years before clinical diagnosis of Parkinson’s disease (PD), Dementia with Lewy bodies (DLB) or Multiple System atrophy (MSA), mild motor and non-motor prodromal manifestations can already be detected. In-depth clinical phenotyping of prodromal synucleinopathies could aid patient stratification in future clinical trials.
Design/Methods:
Eighty-five people with iRBD (mean age at inclusion 69.2 ± 8.7 years, 23F) included between 2004 and 2019, were followed longitudinally until they fulfilled clinical diagnostic criteria (i.e. ‘phenoconversion’) for either Parkinson’s disease (n = 40), Dementia with Lewy bodies (n = 39) or Multiple System atrophy (n = 6) [range of follow-up time 1 to 12 years]. Comprehensive clinical assessments of motor and non-motor symptoms were performed annually. Ninety-three healthy controls underwent the same clinical evaluations. Tracing backwards from phenoconversion, clinical outcomes of iRBD were compared with expected scores for age-matched healthy controls, and between iRBD subgroups, at each time point.
Results:
Motor symptoms and signs, measured with MDS-UPDRS part II and III, showed significant worsening in iRBD compared to healthy ageing six years before phenoconversion, while quantitative motor function tests showed abnormalities four to five years ahead. Smell showed the earliest changes with detection of hyposmia 11 years prior to phenoconversion. Cognitive impairment and abnormal color vision were identified five and two years before diagnosis, respectively. Autonomic dysfunction preceded disease onset with approximately 8 years. DLB showed earlier cognitive impairment and abnormal color vision compared to PD.
Conclusions:
In comparison to healthy ageing, the iRBD group showed evident motor and non-motor impairment years before the clinical diagnosis of a manifest synucleinopathy was made. The earliest change was detection of hyposmia 11 years prior to phenoconversion.