Progression Follow up of the First-degree Relatives of Patients With REM Sleep Behavior Disorder

Plain-language summary

REM sleep behavior disorder is a novel and distinct parasomnia characterized by recurrent dream enactment behaviors (DEBs) and polysomnographic features of REM sleep without atonia (RSWA), with typical onset age at early 60's. Idiopathic RBD (iRBD) has been suggested as a most specific precursor of α-synucleinopathy-related neurodegeneration (e.g. Parkinson's disease (PD)). There are increasing reports of positive familial cases in both iRBD and PD. In the past few years, the investigators have established the baseline data of a case-control family cohort of iRBD (208 first-degree relatives (FDR) of patients with iRBD and 204 FDRs of controls). Not only did the investigators confirm the familial aggregation of iRBD with neurodegeneration and iRBD cases, the investigator also found that the FDRs harbored a spectrum of isolated RBD features (including DEBs, REM- sleep behavioral events, and RSWA). Besides, when compared with control-FDRs, iRBD-FDRs patients showed more prodromal markers of neurodegeneration (including possible/probable RBD, excessive daytime sleepiness, constipation, and subthreshold parkinsonism) as suggested by the International Parkinson and Movement Disorder Society (MDS) research criteria. The promising baseline findings paved the way for the current proposed prospective study of this unique family cohort. In addition, around 85 unaffected FDRs from each group has repeated the assessments at a mean follow-up duration of about 4 years (early termination of the study supported by RGC- ECS Ref no. 24117018; reason for early termination - ECS PI applicant left the University at early 2020), the preliminary data indicated a persistent familial aggregation of RBD symptoms, loading of prodromal markers (e.g. possible RBD, subthreshold parkinsonism), and a seemingly faster progression into prodromal RBD among the FDRs of iRBD than that of control. This current proposed study is a prospective study with a mean of 7-year follow-up interval to monitor the progression of α- synucleinopathy neurodegeneration and related markers. With the rolling recruitment, the investigators now have 230 control-FDRs and 250 iRBD-FDRs, from which the investigators expect 200 FDRs of each group may respond to the follow-up study. A series of prodromal markers related to neurodegeneration including clinical and sleep assessment (e.g. autonomic symptoms, motor signs, neurocognitive function, sleepiness, vPSG and one-week actigraphy) that were measured at baseline will be reassessed. Specifically, home PSG with a body-movement monitoring system will be additionally implemented in the proposed study to empower the identification of RBD features, especially during the COVID pandemic period at which hospital accessibility is restricted. In addition, the development of clinical neurodegenerative diseases will be ascertained. This proposed study, by recruiting FDRs of iRBD patients (and controls) with prospective study design, will provide novel and important information on the progression of prodromal makers of α-synucleinopathy neurodegenerative diseases in a high-risk population and facilitate further genetic/omics and future neuroprotective intervention study of the familial iRBD.

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