Changes in serum uric acid, glutathione, and amyloid-β1-42 levels in Parkinson’s disease patients and their association with disease progression and cognitive decline

This study aims to evaluate the diagnostic significance of serum uric acid (UA), glutathione (GSH), and amyloid-β1-42 (Aβ1-42) levels in relation to disease progression and cognitive impairment in patients with Parkinson’s disease (PD). A total of 209 PD patients with disease duration ranging from 4.0 to 6.8 years were enrolled. Based on the Hoehn-Yahr staging system, patients were classified into Early (n = 67), Medium-term (n = 70), and Advanced (n = 72) stages. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), dividing the cohort into CD (cognitive dysfunction, n = 94) and NO-CD (no cognitive dysfunction, n = 115) groups. Serum UA, GSH, and Aβ1-42 levels were analyzed for correlations with clinical data. Independent risk factors and diagnostic value were determined through multivariable logistic regression models and receiver operating characteristic curve analysis. Serum UA and GSH levels progressively declined with advancing disease stage, while Aβ1-42 increased. Compared to the NO-CD group, the CD group showed lower serum UA and GSH levels, and higher Aβ1-42 levels. Serum UA and GSH were inversely correlated with disease duration, levodopa equivalent daily dose, and Unified Parkinson's Disease Rating Scale scores, while Aβ1-42 showed positive correlations. UA (<i>p</i> = 0.006), GSH (<i>p</i> &lt; 0.001), and Aβ1-42 (<i>p</i> = 0.040) were independent predictors of disease stage. Similarly, UA (<i>p</i> = 0.003), GSH (<i>p</i> &lt; 0.001), and Aβ1-42 (<i>p</i> &lt; 0.001) were independent predictors of cognitive dysfunction. The combined assessment of these markers demonstrated a higher area under the curve (AUC) than individual markers for disease and cognitive decline identification. Serum UA, GSH, and Aβ1-42 are independent predictors of disease progression and cognitive decline in PD patients. Their combined use offers enhanced diagnostic accuracy for disease staging and cognitive impairment in PD.

本研究旨在评估血清尿酸（serum uric acid, UA）、谷胱甘肽（glutathione, GSH）及淀粉样蛋白β1-42（amyloid-β1-42, Aβ1-42）水平与帕金森病（Parkinson’s disease, PD）患者疾病进展及认知损害的关联诊断价值。本研究共纳入209例病程为4.0~6.8年的PD患者，依据Hoehn-Yahr分期系统将其分为早期组（n=67）、中期组（n=70）及晚期组（n=72）。采用简易精神状态检查（Mini-Mental State Examination, MMSE）评估患者认知功能，将队列划分为认知功能障碍组（cognitive dysfunction, CD，n=94）与非认知功能障碍组（NO-CD，n=115）。分析血清UA、GSH及Aβ1-42水平与临床数据的相关性；通过多变量logistic回归模型及受试者工作特征曲线分析，确定相关独立危险因素及诊断价值。结果显示，随着疾病分期升高，血清UA与GSH水平呈进行性下降，而Aβ1-42水平则升高。与NO-CD组相比，CD组患者血清UA、GSH水平更低，Aβ1-42水平更高。血清UA与GSH水平与疾病病程、左旋多巴等效日剂量及统一帕金森病评定量表评分呈负相关，而Aβ1-42则呈正相关。UA（p=0.006）、GSH（p<0.001）及Aβ1-42（p=0.040）均为疾病分期的独立预测因子。同理，UA（p=0.003）、GSH（p<0.001）及Aβ1-42（p<0.001）均为认知功能障碍的独立预测因子。联合检测上述标志物的曲线下面积（area under the curve, AUC）高于单一标志物检测，可更好地识别疾病进展与认知衰退。综上，血清UA、GSH及Aβ1-42水平可作为PD患者疾病进展与认知衰退的独立预测因子，联合检测可提升PD患者疾病分期与认知损害的诊断准确性。