A Population‐Based Approach to the Argument on Brain‐First and Body‐First Pathogenesis of Lewy Body Disease

Abstract

ObjectiveTo explore the clinical progression of the brain‐/body‐first categories within Lewy body disease (LBD): Parkinson's disease (PD), dementia with Lewy bodies (DLB), and PD dementia.MethodsWe used of the Rochester Epidemiology Project to establish a population‐based cohort of clinically diagnosed LBD. We used two definitions for differentiating between brain‐ and body‐first LBD: a previously hypothesized body‐first presentation in patients with rapid eye movement sleep behavior onset before motor symptoms onset; and an expanded definition of body‐first LBD when a patient had at least 2 premotor symptoms between constipation, erectile dysfunction, rapid eye movement sleep behavior, anosmia, or neurogenic bladder.ResultsBrain‐first patients were more likely to be diagnosed with PD (RR = 1.43, p = 0.003), whereas body‐first patients were more likely to be diagnosed with DLB (RR = 3.15, p < 0.001). Under the expanded definition, there was no difference in LBD diagnosis between brain‐first and body‐first patients (PD: RR = 1.03, p = 0.10; DLB: RR = 0.88, p = 0.58) There were no patterns between brain‐ or body‐first presentation, PD dementia under either definition (original: p = 0.09, expanded: p = 0.97), and no significant difference in motor symptoms between brain‐first and body‐first.InterpretationOur findings do not support the dichotomous classification of body‐first and brain‐first LBD with the currently proposed definition. Biological exposures resulting in PD and DLB are unlikely to converge on a binary classification of top‐down or bottom‐up synuclein pathology. ANN NEUROL 2024;96:551–559