Abstract Details

Title Prospective Clinical Evolution in People with Prodromal Synucleinopathies

Topic Movement Disorders

Presentation(s) S2 - Movement Disorders: Epidemiology and Clinical Aspects (2:48 PM-3:00 PM)

Poster/Presentation
Number 010

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.

Objective To assess clinical features and changes in idiopathic REM-sleep behavior disorder (iRBD) the decade before clinical diagnosis of a manifest neurodegenerative disorder.

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.

Authors/Disclosures
Aline Delva, Jr., MD (Montreal Neurological Institute) PRESENTER	Dr. Delva has received research support from Research Foundation - Flanders.
Seyed-Mohammad Fereshtehnejad, MD, PhD	Dr. Fereshtehnejad has nothing to disclose.
Chun Yao (Universté de Montréal)	No disclosure on file
Amelie Pelletier (Montreal General Hospital)	Ms. Pelletier has nothing to disclose.
Jacques Montplaisir, MD, PhD	The institution of Dr. Montplaisir has received research support from CIHR.
Jean-François Gagnon	No disclosure on file
Ronald Postuma, MD (Montreal General Hospital)	Dr. Postuma has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche, Biogen, Takeda, Theranexus, GE, Jazz, Curasen, Paladin, Inception Sciences, Phytopharmics, Vaxxinity, Merck. Dr. Postuma has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen/Partners. The institution of Dr. Postuma has received research support from CIHR, Weston Foundation, Webster Foundation, Roche, MJFF, Parkinson Canada, FRSQ, NIH.