Neurodegeneration, REM Sleep Behavior Disorder
Conditions
Keywords
REM sleep behavior disorder, Neurodegeneration, α-synucleinopathy, Prodromal markers
Brief summary
This study is a prospective study with a mean of 7-year follow-up interval, aims to monitor the progression of α-synucleinopathy neurodegeneration by the evolution of prodromal markers and development of clinical disorders in patients with idiopathic REM Sleep Behavior Disorder (iRBD) and healthy controls.
Detailed description
REM sleep behavior disorder (RBD) is a parasomnia characterized by dream enactment behaviors and REM sleep without muscle atonia (excessive EMG activity) during REM sleep.Increasing studies revealed that iRBD eventually converts to α-synucleinopathy, such as Parkinson's disease (PD), dementia with Lewy Bodies (DLB), and multiple system atrophy (MSA). Recent studies reported that over 80% of patients with iRBD eventually developed neurodegeneration at a mean interval of 14 years after iRBD onset or diagnosed. Thus, iRBD is regarded as a precursor of α-synucleinopathies. In addition to iRBD, a large series of other non-motor symptoms also present before the emergence of typical motor symptoms of PD, including autonomic dysfunction, olfactory loss, color vision impairment, neurocognitive impairment,neuroimaging of dopamine dysfunction, daytime sleepiness, and psychiatric disorders. In recent years, several longitudinal studies have found that patients with iRBD with a higher rate of these markers may have a faster progression of neurodegeneration. On the other hand, a variety of external risk factors of PD including environmental toxic exposure, lifestyle factors, and some medications have long been recognized, which affect numerous fundamental cellular processes by interaction with genetic predisposition. However, several knowledge gaps still need further studies to uncover. First, few studies have explored the predictive value of dynamic change of biomarkers in prodromal stage of PD. Second, few previous prospective studies also employed a control group to compare the change of these prodromal markers between patients and healthy controls over time. Third, as some of previous studies employed a retrospective study design, potential recall bias may contaminate the results. Moreover, the sample sizes of most previous studies investigating biomarkers were relative small (n \< 80) and follow-up durations in most study are relatively short, which may have limited the statistical power to detect the risk factors with mild to moderate effect size. Finally, as previous reported longitudinal studies of iRBD mainly focused on Caucasian or other ethnic groups, there is only limited data about neurodegenerative biomarkers in Chinese iRBD. In conclusion, prospective longitudinal studies with larger sample size, regular follow-up, and relative long follow-up duration are needed to better map the progression of neurodegeneration.
Interventions
None listed
Sponsors
Chinese University of Hong Kong
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
for iRBD at baseline: 1. Fulfilling the diagnostic criteria for iRBD. As patients with iRBD were recruited during a long period, the diagnosis of RBD was based on ICSD and ICSD-2 (before 2014), and ICSD-3 (2014 and thereafter) criteria. The diagnosis for all patients were confirmed by video-PSG. In summary, patient diagnosed with RBD should present excessive EMG activity during REM sleep on video-PSG assessment and report a history of repeated dream enactment behaviors; 2. Having neurocognitive test and neurological examination since 2008; 3. Free of neurodegenerative diseases at the last visit. for controls without iRBD at baseline: 1. Age- and sex- matched with patients with iRBD; 2. Free of narcolepsy and other neurological diseases; 3. Without any RBD features as confirmed by both clinical history and video-PSG; 4. Without neurodegenerative diseases; 5. Having neurocognitive test and neurological examination at baseline.
Exclusion criteria
1. Patients with narcolepsy; 2. Patients with known neurodegenerative diseases; 3. Pseudo-RBD (e.g., RBD symptoms were eliminated after severe obstructive sleep apnea had treated with continuous positive airway pressure therapy.); 4. Early-onset RBD (e.g., before the age of 50 years old) which might have a different pathogenesis from iRBD.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The overall conversion rate of iRBD to neurodegenerative diseases | Changes from baseline to 7 year follow up | The overall conversion rate of iRBD to neurodegenerative diseases. The diagnoses of neurodegenerative diseases will be ascertained by neurologists according to the standard diagnostic criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes of the likelihood ratio of probability of prodromal Parkinson's disease in each individual | Baseline and 7 year | The dynamic changes of the likelihood ratio of probability of prodromal Parkinson's disease in the patients with iRBD and healthy controls will be calculated based on the Movement Disorder Society (MDS) research criteria for prodromal Parkinson's disease. |
| Conversion rate of iRBD to neurodegenerative diseases in patients with high and low likelihood ratio of probability of prodromal Parkinson's disease in each individual | Changes from baseline to 7 year follow up | Conversion rate of iRBD to neurodegenerative diseases in patients with high and low likelihood ratio of probability at baseline, the level of likelihood ratio was defined based on the Movement Disorder Society (MDS) research criteria for prodromal Parkinson's disease. |
Countries
Hong Kong
Contacts
Primary ContactJihui Zhang, PhD
Outcome results
None listed