卒中后认知障碍（PSCI）是严重影响脑卒中患者生存质量的常见并发症。肠道菌群代谢物氧化三甲胺（TMAO）被认为是心血管疾病的重要驱动因子。基础研究发现肠道菌群紊乱及TMAO异常在脑卒中进展和认知功能衰退过程中发挥作用。而血液中TMAO与PSCI关联的前瞻性研究未见报道。本项目依托已建立的缺血性脑卒中队列，采用高效液相色谱串联质谱法检测血浆TMAO和前体物（胆碱、甜菜碱和L-肉毒碱）水平，分析血浆TMAO及前体物与PSCI的关联；探讨炎症和内皮功能机制在TMAO及前体与PSCI关联之间的作用；进一步联合TMAO及前体物、前期工作发现的反映不同病理通路的缺血性脑卒中不良预后预测蛋白和传统危险因素构建PSCI预测模型，模型同时考虑导致PSCI发病的多病理途径，可精准地识别PSCI高危患者。本研究将为血浆TMAO及前体物作为PSCI预测标志提供重要的流行病学证据，为PSCI的预防和控制提供新思路。

Post-stroke cognitive impairment (PSCI) is a common complication of stroke that seriously reduces the quality of life. Intestinal metabolite trimethylamine N-oxide (TMAO) is regarded as an important driver of cardiovascular disease. Experimental studies indicate that intestinal flora disturbance and elevated TMAO levels play a role in the progression of stroke and cognitive decline. Prior studies have indicated that TMAO can change intestinal epithelial permeability, affect systemic immune response, aggravate inflammatory response, induce endothelial cell dysfunction and stimulate mitochondrial oxidative stress, while all these pathological processes could cause neurological damage. However, no prospective study on the association between plasma TMAO and PSCI has been reported. This project is conducted among the ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). Plasma TMAO concentrations will be measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). We will first investigate the associations of plasma TMAO and precursor (choline, betaine and L-carnitine) with PSCI, and then explore the role of inflammation and endothelial functional mechanisms in the relationships between TMAO and precursors with PSCI. In addition, we will further construct a PSCI prediction model by combining plasma TMAO and precursors, multiple biomarkers covering distinct pathways, and traditional risk factors. This model involves multiple pathologic pathways leading to the onset of PSCI, which is more comprehensive, and can accurately screen and identify high-risk PSCI patients. Our project will provide important epidemiological evidence for the use of plasma TMAO and precursors as predictive markers of PSCI, and will provide new insights for the prevention and control of PSCI.