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.

帕金森病 (PD) 中发生的无法解释的体重变化经常被忽视，并且仍然是帕金森病患者的非运动特征知之甚少。已经描述了一种特定的低体重“公园体重”表型，我们的目的是评估 PD 体重变异的临床和预后轨迹以及生物标志物。我们从 PPMI 数据库中评估了 405 名新发 PD 患者和 187 名健康对照 (HC) 的体重相关生物标志物，随访时间为 5 年。体重变异性定义为访问之间体重的个体内变异性。 PD患者被分类为体重减轻者、体重增加者或体重稳定的患者。使用线性混合效应模型探讨了组间运动和非运动临床变量的差异进展。最后，我们估计了体重的纵向变化作为基线和纵向纹状体突触前多巴胺能转运蛋白成像的函数。与 HC 患者相比，PD 患者的体重变异性更大 ( p = 0.003)。体重减轻的患者基线时脑脊液淀粉样蛋白 1-42 较低 ( p = 0.009)。此外，与体重稳定的患者相比，体重减轻的患者表现出更快的认知能力下降（ p = 0.001），而体重增加的患者则表现出较慢的运动进展（ p = 0.001）。基线右侧纹状体去神经是 PD 患者和 HC 患者体重变异性的预测因子 ( p < 0.001)。同样，PD 患者的体重变异性与右侧纹状体去神经的进展相关 ( p < 0.001)。 与 HC 相比，PD 患者的体重变异性和特别是体重减轻更为常见，并且与特定的运动、非运动和认知进展模式相关。随后体重减轻的患者在基线时存在较大的脑脊液淀粉样蛋白负荷。右侧纹状体的突触前多巴胺能成像可以作为 PD 和 HC 未来体重变化的预测因子。