Objective: To determine whether the body-first versus brain-first hypothesis of Parkinson’s disease (PD) can be reliably applied at the individual patient level using multimodal clinical and imaging markers.
Background: The brain-first versus body-first model of PD proposes two distinct trajectories of disease initiation and propagation. Body-first PD involves early peripheral autonomic pathology, including REM sleep behavior disorder (RBD) and abnormal cardiac sympathetic imaging, whereas brain-first PD is thought to originate centrally before spreading peripherally. However, substantial criticism has recently been raised about this dichotomous model, largely derived from group-level data and its applicability to individual patients remains unclear.
Method: We assessed twenty patients with early PD (≤ 2 years since diagnosis) using multimodal assessments consisting of detailed clinical evaluations, including the total MDS-UPDRS scale and several questionnaires, 123I-MIBG cardiac scintigraphy, DAT-SPECT imaging, RBD evaluation, olfactory testing and autonomic testing. Patients were classified as body-first when 123I-MIBG uptake was abnormal (late heart-to-mediastinum (H/M) ratio < 1.6) and as brain-first when uptake was normal (late H/M ratio ≥ 1.6). We then compared both subtypes in terms of RBD status and other clinical features.
Results: RBD status emerged as the strongest individual-level classification marker, correctly classifying 85% of patients. Other clinical and imaging features showed substantial overlap between subtypes.
Conclusion: Our results suggest that body-first and brain-first PD may exist along a pathophysiological continuum, and that differentiation at the individual level for most symptoms is limited, with the exception of RBD. RBD may represent the strongest individual-level marker of body-first PD and could serve as a cost-effective screening tool.
To cite this abstract in AMA style:
K. Colman, I. de Volder, S. Ceyssens, J. Verbraecken, M. Viaene, O. Wolfgang, A. Janzen, A. Pijpers, D. Crosiers, F. Dijkstra. Brain-First and Body-First Model Translated to Individual-Level Characterization in Parkinson’s Disease: Multimodal Imaging and Clinical Approach [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/brain-first-and-body-first-model-translated-to-individual-level-characterization-in-parkinsons-disease-multimodal-imaging-and-clinical-approach/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/brain-first-and-body-first-model-translated-to-individual-level-characterization-in-parkinsons-disease-multimodal-imaging-and-clinical-approach/