Clinical implications of malnutrition in Huntington's disease progression: evidence from a Chinese cohort and Mendelian randomization

作者：Jie-Qiang Xia, Yangfan Cheng, Sirui Zhang, Yuanzheng Ma, Jia-Jia Fu, Tian-Mi Yang, Ling-Yu Zhang, Jean-Marc Burgunder, Hui-Fang Shang · 发表于：Frontiers in Nutrition · 年份：2026 · DOI：10.3389/fnut.2026.1718264 · 研究领域：Genetic Neurodegenerative Diseases、Amyotrophic Lateral Sclerosis Research、Fibromyalgia and Chronic Fatigue Syndrome Research

Background: Huntington's disease (HD) is a neurodegenerative disorder associated with progressive motor, cognitive, and psychiatric dysfunction. Peripheral metabolic disturbances, including malnutrition, are commonly observed in HD. However, the prevalence, clinical correlations, and prognostic value of malnutrition in HD, especially among Chinese patients, remain inadequately explored. Methods: This cohort study recruited 113 genetically confirmed HD patients and 113 age/sex-matched healthy controls (HCs). Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score, Geriatric Nutritional Risk Index (GNRI), and Prognostic Nutritional Index (PNI). Clinical evaluations included Unified Huntington's Disease Rating Scale (UHDRS), cognitive tests, and psychiatric assessments. Kaplan-Meier survival analysis and Cox regression models were used to evaluate the prognostic significance of malnutrition. Mendelian randomization (MR) analysis was employed to explore causal relationships between nutritional indicators and HD progression using genome-wide association study (GWAS) data. Results: During a mean follow-up of 5.74 years, 44 patients reached composite endpoints of death or loss of independent function [total functional capacity (TFC) ≤ 2]. HD patients showed higher malnutrition prevalence than HCs (CONUT: 34.51 vs. 13.27%; GNRI: 7.96 vs. 2.65%). Malnutrition correlated with functional decline, cognitive impairment, advanced disease stage, and lower comp...