When the Scale Drops: Pathways to Weight Loss in Parkinson's Disease and Future Directions.

Although Parkinson's disease (PD) is classically defined by its motor features, non-motor symptoms exert a substantial and often under-recognized influence on disease trajectory. Among these, weight loss has long been observed in PD and other neurodegenerative disorders, yet the mechanisms remain incompletely understood. This limited mechanistic insight has left few treatment options for weight loss in PD. Emerging research highlights the role of metabolic regulation, neuroendocrine signaling, pharmacologic treatment, cognitive decline, gastrointestinal dysfunction, and brain stimulation in shaping weight trajectories in PD. In this review, we synthesize current evidence surrounding weight in PD, beginning with an overview of epidemiologic trends and their implications for morbidity and mortality. The sections that follow examine proposed mechanisms, clinical and treatment-related factors associated with weight change, and insights derived from deep brain stimulation studies. Finally, we summarize cross-mechanism interactions, current knowledge gaps and discuss practical recommendations for translating these insights into therapeutic strategies. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.