Cognitive training and promoting a healthy lifestyle for individuals with isolated REM sleep behavior disorder: study protocol of the delayed-start randomized controlled trial CogTrAiL-RBD.

BACKGROUND: Isolated REM sleep behavior disorder (iRBD) is an early α-synucleinopathy often accompanied by incipient cognitive impairment. As executive dysfunctions predict earlier phenotypic conversion from iRBD to Parkinson's disease and Lewy body dementia, cognitive training focusing on executive functions could have disease-modifying effects for individuals with iRBD. METHODS: The study CogTrAiL-RBD investigates the short- and long-term effectiveness and the feasibility and underlying neural mechanisms of a cognitive training intervention for individuals with iRBD. The intervention consists of a 5-week digital cognitive training accompanied by a module promoting a healthy, active lifestyle. In this monocentric, single-blinded, delayed-start randomized controlled trial, the intervention's effectiveness will be evaluated compared to an initially passive control group that receives the intervention in the second, open-label phase of the study. Eighty individuals with iRBD confirmed by polysomnography will be consecutively recruited from the continuously expanding iRBD cohort at the University Hospital Cologne. The evaluation will focus on cognition and additional neuropsychological and motor variables. Furthermore, the study will examine the feasibility of the intervention, effects on physical activity assessed by accelerometry, and interrogate the intervention's neural effects using magnetic resonance imaging and polysomnography. Besides, a healthy, age-matched control group (HC) will be examined at the first assessment time point, enabling a cross-sectional comparison between individuals with iRBD and HC. DISCUSSION: This study will provide insights into whether cognitive training and psychoeducation on a healthy, active lifestyle have short- and long-term (neuro-)protective effects for individuals with iRBD. TRIAL REGISTRATION: The study was prospectively registered in the German Clinical Trial Register (DRKS00024898) on 2022-03-11, https://drks.de/search/de/trial/DRKS00024898 . PROTOCOL VERSION: V5 2023-04-24.

Detecting Misfolded α-Synuclein in Blood Years before the Diagnosis of Parkinson's Disease.

BACKGROUND: Identifying individuals with Parkinson's disease (PD) already in the prodromal phase of the disease has become a priority objective for opening a window for early disease-modifying therapies. OBJECTIVE: The aim was to evaluate a blood-based α-synuclein seed amplification assay (α-syn SAA) as a novel biomarker for diagnosing PD in the prodromal phase. METHODS: In the TREND study (University of Tuebingen) biennial blood samples of n = 1201 individuals with/without increased risk for PD were taken prospectively over 4 to 10 years. We retrospectively analyzed blood samples of 12 participants later diagnosed with PD during the study to detect and amplify pathological α-syn conformers derived from neuronal extracellular vesicles using (1) immunoblot analyses with an antibody against these conformers and (2) an α-syn-SAA. Additionally, blood samples of n = 13 healthy individuals from the TREND cohort and n = 20 individuals with isolated rapid eye movement sleep behavior disorder (iRBD) from the University Hospital Cologne were analyzed. RESULTS: All individuals with PD showed positive immunoblots and a positive α-syn SAA at the time of diagnosis. Moreover, all PD patients showed a positive α-syn SAA 1 to 10 years before clinical diagnosis. In the iRBD cohort, 30% showed a positive α-syn SAA. All healthy controls had a negative SAA. CONCLUSIONS: We here demonstrate the possibility to detect and amplify pathological α-syn conformers in peripheral blood up to 10 years before the clinical diagnosis of PD in individuals with and without iRBD. The findings of this study indicate that this blood-based α-syn SAA assay has the potential to serve as a diagnostic biomarker for prodromal PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.