Plasma trimethylamine N-oxide, carnitine, choline, and betaine distinguish cognition impairment in Parkinson's disease.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

TMAO and its metabolic precursors are potential biomarkers for early identification of cognitive dysfunction, offering timely opportunities for intervention in PD patients.