Objective: To study the temporal evolution of biomarkers of various modalities in healthy ageing controls (HC), the prodromal condition of isolated REM sleep behavior disorder (iRBD) and the overt motor Parkinson’s disease (PD).

Background: At the time of PD diagnosis the neurodegenerative process of aggregating alpha-synuclein (aSyn) and neuronal loss is already advanced and the prodromal phase needs to be studied. iRBD represents a highly specific prodromal condition for the development of aSyn aggregation disorders with annual conversion rates to disease of about 6%. Biomarkers to understand the early progressing neurodegeneration and to objectively reflect the evolution of overt disease in the early phase are needed to support clinical trials with putative neuroprotective agents.

Methods: DeNoPa is a single center, longitudinal observational study to evaluate progressing neurodegeneration. Assessments at baseline and follow-up after 24 months included questionnaires on non-motor signs (NMS), cognitive testing, video-polysomnography (PSG), electrocardiogram (ECG), olfactory testing, magnetic resonance imaging with voxel based morphometry (VBM) and cerebrospinal fluid (CSF) measures (1).

Results: We investigated previously identified biomarkers for early PD in 34 iRBD subjects and compared these to 88 HC and 91 PD patients. Most biomarkers in the iRBD group feature between HC and the PD group. ECG frequency was elevated in PD, but normal in iRBD and HC. Other biomarkers already show abnormalities similar to PD such as the high NMS burden, decreased beta-amyloid 1-42 and total tau protein in CSF. There was also a trend towards more marked abnormalities in iRBD compared to the PD group, such as more severe hippocampal atrophy by VBM, more pronounced cognitive decline, visuospatial deficits and lower CSF aSyn.

Conclusions: In prodromal PD abnormalities in NMS, imaging and fluidic markers are already obviously pointing towards the development of overt disease. Based on these results iRBD may represent a prodromal state of various aSyn aggregation disorders and suggests development of a specific phenotype with more rapid hippocampal atrophy, lower CSF aSyn and early cognitive decline.

References: (1) Mollenhauer B, Zimmermann J, Sixel-Doring F, et al. Monitoring of 30 marker candidates in early Parkinson disease as progression markers. Neurology. Jul 12 2016;87(2):168-177.

« Back to 2018 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/temporal-evolution-of-biomarkers-from-healthy-ageing-isolated-rem-sleep-behavior-to-early-parkinsons-disease/