Clinical trajectories and biomarkers for weight variability in early Parkinson’s disease
Daniele Urso, Daniel J. van Wamelen, Lucia Batzu, Valentina Leta, Juliet Staunton, José A. Pineda‐Pardo, Giancarlo Logroscino, Jagdish C. Sharma, К. Ray Chaudhuri
Abstract
Unexplained weight changes that occur in Parkinson's disease (PD), are often neglected and remain a poorly understood non-motor feature in patients with PD. A specific 'Park-weight' phenotype with low body weight has been described, and our aim was to evaluate the clinical and prognostic trajectories and biomarkers of weight variability in PD. We evaluated body weight-related biomarkers in 405 de novo PD patients and 187 healthy controls (HC) over a 5-year follow-up period from the PPMI database. Body-weight variability was defined as intra-individual variability in body weight between visits. PD patients were categorized as weight losers, gainers, or patients with stable weight. The differential progression of motor and non-motor clinical variables between groups was explored using linear mixed-effects models. Finally, we estimated longitudinal changes in weight as a function of baseline and longitudinal striatal presynaptic dopaminergic transporter imaging. PD patients presented a greater weight variability compared to HC (p = 0.003). Patients who developed weight loss had lower CSF amyloid-beta 1-42 (p = 0.009) at baseline. In addition, patients with weight loss showed a faster cognitive decline (p = 0.001), whereas patients with weight gain showed a slower motor progression (p = 0.001), compared to patients with stable weight. Baseline right striatal denervation was a predictor of weight variability in both PD patients and HC (p < 0.001). Similarly, weight variability in PD patients was associated with the progression of right striatal denervation (p < 0.001). Weight variability and specifically weight loss are more frequent in PD compared to HC, and are associated with specific motor, non-motor and cognitive progression patterns. A greater CSF amyloid burden was present at baseline in patients with subsequent weight loss. Presynaptic dopaminergic imaging in the right striatum may serve as a predictor of future weight changes in PD and HC.