Prodromal Markers in Recurrent Dream Enactment Behaviors Without REM Sleep Without Atonia

Striatal Dopamine Transmission and Prodromal Markers of α-synucleinopathy Neurodegeneration in Recurrent Dream Enactment Behaviors Without REM Sleep Without Atonia: a Case-control Study

REM sleep behavior disorder is a novel and distinct parasomnia characterized by recurrent dream enactment behaviors (DEBs) and REM sleep without atonia (RSWA) during polysomnographic assessment, with a male predominance and typical onset age at early 60's. The majority of patients with idiopathic RBD (iRBD) will eventually develop α-synucleinopathy, for instance Parkinson's disease (PD). Thus, iRBD has been considered as a highly specific precursor of α-synucleinopathy-related neurodegeneration. Recently, increasing studies have found that some participants present with only RSWA or DEBs (but without sufficient RSWA), which does not meet the diagnostic criteria for RBD. It has been suggested that these participants with subclinical features (either DEBs or RSWA) might represent a condition known as prodromal RBD. Several emerging evidence, including our own study, have implied a link between isolated RSWA (RSWA without DEBs) and markers of α-synucleinopathy-related neurodegeneration. However, it is still unclear whether the other condition related to RBD, i.e. recurrent DEBs but without sufficient RSWA, is related to a certain degree of α-synucleinopathy. In this regard, the novel concept of recurrent DEBs but without sufficient RSWA, also termed as prodromal/isolated RBD by some researchers, requires validation by further evidence in terms of clinical feature and neurodegenerative prodromal markers perspectives.

This proposed study is a case-control study, which aims to determine whether recurrent DEBs but without sufficient RSWA represents an early stage of α-synucleinopathy. The investigators will recruit 62 participants with recurrent DEBs but without sufficient RSWA and their age-, sex- matched controls from the community and on-going projects. All participants will undergo clinical interview, comprehensive measures of prodromal markers of neurodegeneration (including excessive daytime sleepiness, olfactory functioning, constipation, erectile dysfunction, urinary dysfunction, symptomatic hypotension, depression, and clinical motor markers) as suggested by the International Parkinson and Movement Disorder Society (MDS) research criteria. In addition, a subset of the sample (n = 26 in each group) will undergo the triple-tracer positron emission tomography/computed tomography (PET/CT) imaging protocol of 18F-DOPA, to determine dopamine functions in putamen. This proposed study will help to disentangle the core features of RBD and validate the concept of prodromal RBD with reference to prodromal markers related to α-synucleinopathy neurodegeneration.

Inclusion Criteria:

• Age between 45 and 65 years old
• RBDQ-HK behavior factor greater > 8
• Recurrent DEBs by interview and/or video analysis
• Absence of sufficient RSWA

Exclusion Criteria:

• Age- and sex- matched with cases
• RBDQ-HK behavior factor < 8
• No DEBs by either interview or video analysis
• Absence of sufficient RSWA