Brain-first body-first model translated to individual-level characterization in Parkinson’s disease: multimodal imaging and clinical approach

The brain-first/body-first hypothesis of Parkinson’s disease (PD) proposes two distinct trajectories of disease initiation and propagation. Body-first PD involves early peripheral (autonomic) pathology, including abnormal cardiac sympathetic imaging and brainstem-related REM-sleep behavior disorder (RBD), whereas brain-first PD is thought to originate centrally before spreading peripherally. Substantial criticism has recently been raised about this dichotomous model, largely derived from group-level data and its applicability to individual patients remains unclear.

We examined to what degree commonly used, clinical and imaging features can assist in classifying individual early PD patients (≤2 years since diagnosis, n = 20) into brain-first and body-first subtypes, using 123I-MIBG scintigraphy as the reference standard. Probable RBD status was the strongest individual-level classification marker, correctly classifying 85% of patients. Other clinical and imaging features performed poor as individual-level classifiers, suggesting substantial overlap, a continuum, and limited individual-level differentiation.

RBD is associated with MIBG-defined body-first PD in this cohort, and may represent a promising, low-cost marker needing further validation. This work was partly funded by the King Baudouin Foundation, Stichting Parkinsonfonds, ROMO foundation and Move for Parkinson. The funders had no role in the study design, data collection, data analysis, publication decision or preparation of the manuscript.

These authors contributed equally: David Crosiers, Femke Dijkstra. Department of Neurology, Antwerp University Hospital, Antwerp, Belgium Kaat Colman, Ilse De Volder, David Crosiers & Femke Dijkstra Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium Kaat Colman, Ilse De Volder & David Crosiers Multidisciplinary Sleep Disorders Centre, Antwerp University Hospital, Edegem, Belgium Department of Nuclear Medicine, Antwerp University Hospital and University of Antwerp, Edegem, Belgium Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Wilrijk, Belgium Laboratory of Sleep Disorders, St. Dimpna Regional Hospital, Geel, Belgium Department of Neurology, St.

Dimpna Regional Hospital, Geel, Belgium Department of Neurology, Philipps University, Marburg, Germany Sleep Medicine Centre Kempenhaeghe, Heeze, The Netherlands The authors declare no competing interests. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

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