Patients with isolated rapid-eye-movement sleep behaviour disorder (RBD) are commonly regarded as being in the early stages of a progressive neurodegenerative disease involving α-synuclein pathology, such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. Abnormal α-synuclein deposition occurs early in the neurodegenerative process across the central and peripheral nervous systems and might precede the appearance of motor symptoms and cognitive decline by several decades. These findings provide the rationale to develop reliable biomarkers that can better predict conversion to clinically manifest α-synucleinopathies. In addition, biomarkers of disease progression will be essential to monitor treatment response once disease-modifying therapies become available, and biomarkers of disease subtype will be essential to enable prediction of which subtype of α-synucleinopathy patients with isolated RBD might develop.

• MeSH
• alfa-synuklein MeSH
• biologické markery * MeSH
• lidé MeSH
• porucha chování v REM spánku komplikace   diagnóza   MeSH
• prognóza MeSH
• progrese nemoci MeSH
• synukleinopatie diagnóza   etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• alfa-synuklein MeSH
• biologické markery * MeSH

Idiopathic REM sleep behaviour disorder (iRBD) is a powerful early sign of Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. This provides an unprecedented opportunity to directly observe prodromal neurodegenerative states, and potentially intervene with neuroprotective therapy. For future neuroprotective trials, it is essential to accurately estimate phenoconversion rate and identify potential predictors of phenoconversion. This study assessed the neurodegenerative disease risk and predictors of neurodegeneration in a large multicentre cohort of iRBD. We combined prospective follow-up data from 24 centres of the International RBD Study Group. At baseline, patients with polysomnographically-confirmed iRBD without parkinsonism or dementia underwent sleep, motor, cognitive, autonomic and special sensory testing. Patients were then prospectively followed, during which risk of dementia and parkinsonsim were assessed. The risk of dementia and parkinsonism was estimated with Kaplan-Meier analysis. Predictors of phenoconversion were assessed with Cox proportional hazards analysis, adjusting for age, sex, and centre. Sample size estimates for disease-modifying trials were calculated using a time-to-event analysis. Overall, 1280 patients were recruited. The average age was 66.3 ± 8.4 and 82.5% were male. Average follow-up was 4.6 years (range = 1-19 years). The overall conversion rate from iRBD to an overt neurodegenerative syndrome was 6.3% per year, with 73.5% converting after 12-year follow-up. The rate of phenoconversion was significantly increased with abnormal quantitative motor testing [hazard ratio (HR) = 3.16], objective motor examination (HR = 3.03), olfactory deficit (HR = 2.62), mild cognitive impairment (HR = 1.91-2.37), erectile dysfunction (HR = 2.13), motor symptoms (HR = 2.11), an abnormal DAT scan (HR = 1.98), colour vision abnormalities (HR = 1.69), constipation (HR = 1.67), REM atonia loss (HR = 1.54), and age (HR = 1.54). There was no significant predictive value of sex, daytime somnolence, insomnia, restless legs syndrome, sleep apnoea, urinary dysfunction, orthostatic symptoms, depression, anxiety, or hyperechogenicity on substantia nigra ultrasound. Among predictive markers, only cognitive variables were different at baseline between those converting to primary dementia versus parkinsonism. Sample size estimates for definitive neuroprotective trials ranged from 142 to 366 patients per arm. This large multicentre study documents the high phenoconversion rate from iRBD to an overt neurodegenerative syndrome. Our findings provide estimates of the relative predictive value of prodromal markers, which can be used to stratify patients for neuroprotective trials.

• Klíčová slova
• Parkinson’s disease, REM sleep behaviour disorder, dementia with Lewy bodies, multiple system atrophy,
• MeSH
• demence s Lewyho tělísky patofyziologie   MeSH
• demence patofyziologie   MeSH
• Kaplanův-Meierův odhad MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• Parkinsonova nemoc patofyziologie   MeSH
• parkinsonské poruchy diagnóza   MeSH
• polysomnografie MeSH
• porucha chování v REM spánku patofyziologie   MeSH
• předpověď metody   MeSH
• prodromální symptomy MeSH
• prognóza MeSH
• progrese nemoci MeSH
• proporcionální rizikové modely MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by repeated episodes of REM sleep-related vocalizations and/or complex motor behaviors. Definite diagnosis of RBD is based on history and polysomnography, both of which are less accessible due to the lack of trained specialists and high cost. While RBD may be associated with disorders like narcolepsy, focal brain lesions, and encephalitis, idiopathic RBD (iRBD) may convert to Parkinson's disease (PD) and other synucleinopathies in more than 80% of patients and it is to date the most specific clinical prodromal marker of PD. Identification of individuals at high risk for development of PD is becoming one of the most important topics for current PD-related research as well as for future treatment trials targeting prodromal PD. Furthermore, concomitant clinical symptoms, such as subtle motor impairment, hyposmia, autonomic dysfunction, or cognitive difficulties, in subjects with iRBD may herald its phenoconversion to clinically manifest parkinsonism. The assessment of these motor and non-motor symptoms in iRBD may increase the sensitivity and specificity in identifying prodromal PD subjects. This review evaluates the diagnostic accuracy of individual rating scales and validated single items for screening of RBD and the role and accuracy of available clinical, electrophysiological, imaging, and tissue biomarkers in predicting the phenoconversion from iRBD to clinically manifest synucleinopathies.

• Klíčová slova
• Parkinson’s disease, RBD, conversion, idiopathic, imaging, non-motor, rating scales, synuclein,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH