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

Abstract 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 123 I-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.