Xu Zhaohan, Chen Hucheng, Zheng Guoyan, Zhang Wei, Wang Jing, Zhang Jian, Gao Qing, Wu Jun, Xue Xue
Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, Jiangsu, China.
Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, Jiangsu, China.
Parkinsonism Relat Disord. 2025 Jun;135:107844. doi: 10.1016/j.parkreldis.2025.107844. Epub 2025 Apr 16.
Trimethylamine N-oxide (TMAO) and its precursors, as intestinal metabolites, have already been explored in Parkinson's disease (PD). However, whether such an association reflects the risk of cognitive impairment (CI) remains unclear. The purpose of this research is to analyze the diagnostic value of TMAO and its precursors in the detection of PD-related CI.
Using high-performance liquid chromatography-tandem mass spectrometry, plasma TMAO and its precursors were detected from 220 healthy controls (HC) and 234 PD patients who underwent cognitive function assessment. 162 PD patients were enrolled in normal cognitive function group (PD-NCI), while 72 in cognitive impairment group (PD-CI). The expression levels of TMAO and its precursors were compared across different groups. The research carried out logistic regression analysis and built receiver operating characteristic (ROC) curves to assess the diagnostic utility of TMAO and its precursors.
Compared to HC, there were higher expression levels of TMAO and precursor carnitine and betaine in the PD and PD-CI groups (p < 0.001). A higher plasma TMAO level exists in PD-CI compared to that of PD-NCI (p < 0.001). After adjusting for differentiating variables, logistic regression analysis substantiated the findings. The combination of TMAO and its precursors demonstrated fine predictive value with high sensitivity and specificity with areas under the ROC curve (AUCs) of 0.880, 0.707, and 0.941 for distinguishing between PD and HC, PD-NCI and PD-CI, and PD-CI and HC, respectively.
TMAO and its metabolic precursors are potential biomarkers for early identification of cognitive dysfunction, offering timely opportunities for intervention in PD patients.
氧化三甲胺（TMAO）及其前体作为肠道代谢产物，已在帕金森病（PD）中得到研究。然而，这种关联是否反映认知障碍（CI）的风险仍不清楚。本研究的目的是分析TMAO及其前体在检测PD相关CI中的诊断价值。
使用高效液相色谱 - 串联质谱法，对220名健康对照者（HC）和234名接受认知功能评估的PD患者检测血浆TMAO及其前体。162名PD患者纳入正常认知功能组（PD - NCI），72名纳入认知障碍组（PD - CI）。比较不同组中TMAO及其前体的表达水平。进行逻辑回归分析并构建受试者工作特征（ROC）曲线，以评估TMAO及其前体的诊断效用。
与HC相比，PD组和PD - CI组中TMAO及其前体肉碱和甜菜碱的表达水平更高（p < 0.001）。与PD - NCI相比，PD - CI组血浆TMAO水平更高（p < 0.001）。在调整区分变量后，逻辑回归分析证实了这些发现。TMAO及其前体的组合显示出良好的预测价值，具有高敏感性和特异性，区分PD与HC、PD - NCI与PD - CI以及PD - CI与HC的ROC曲线下面积（AUC）分别为0.880、0.707和0.941。
TMAO及其代谢前体是早期识别认知功能障碍的潜在生物标志物，为PD患者提供了及时的干预机会。
