Abstract
Parkinson's disease, Lewy Body dementia and Multiple System Atrophy are classified as alpha-synucleinopathies, sharing alpha-synuclein aggregation as their underlying pathology. Sleep disturbances, particularly REM-sleep behavior disorder (RBD), manifest early in alpha-synucleinopathies, preceding motor and cognitive symptoms. RBD, characterized by REM sleep without atonia (RSWA) and dream-enacting behavior, is the most specific prodromal stage of alpha-synucleinopathies. RBD occur years before the onset of motor and/or cognitive symptoms and formal diagnosis. Isolated RSWA without RBD indicates an even earlier stage. Differentiating iRSWA patients at risk of alpha-synucleinopathies from other causes is crucial for accurate and early diagnosis. In this research project we will assess biomarkers for neurodegeneration in individuals with iRSWA as early manifestations of alpha-synucleinopathies, with a primary focus on Parkinson's disease. These biomarkers include [123I-MIBG] myocardial scintigraphy, olfactory function and alpha-synuclein levels in blood. Additionally, we will investigate whether these biomarkers can distinguish different alpha-synucleinopathies, allowing for a more precise prediction of whether an individual with iRSWA is more likely to develop PD, DLB or MSA. This diagnostic approach facilitates early specialist referral for prodromal screening, enabling early diagnosis, patient stratification for disease-modifying treatments, intervention and follow-up care, and potential inclusion in neuroprotective clinical trials.
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