Plasma Phenylacetylglutamine and Cognitive Impairment After Ischemic Stroke

Phenylacetylglutamine was reported to be associated with ischemic stroke and cognitive performance, but its association with poststroke cognitive impairment (PSCI) remained unclear. We aimed to prospectively investigate the association between plasma phenylacetylglutamine levels and PSCI at 3 months in a multicenter cohort study.

A total of 617 patients with ischemic stroke were included on the basis of a preplanned ancillary study from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). PSCI was evaluated using the Mini-Mental State Examination scale and Montreal Cognitive Assessment scale. Logistic regression analyses were performed to evaluate the association between plasma phenylacetylglutamine and the risk of 3-month PSCI.

According to the Mini-Mental State Examination score, a total of 376 participants developed PSCI at 3 months. After adjustment for age, sex, education, and other important risk factors, the multivariable-adjusted odds ratio of PSCI for the highest tertile of phenylacetylglutamine was 2.16 (95% CI, 1.32-3.54; P_trend=0.002) compared with the lowest tertile. A multiple-adjusted spline regression model showed a positive linear association of plasma phenylacetylglutamine levels with PSCI at 3 months (P for linearity<0.001). Adding plasma phenylacetylglutamine to conventional risk factors significantly improved the risk reclassification of PSCI (net reclassification improvement: 21.35%, P=0.019; integrated discrimination index: 1.78%, P=0.003). Similar significant findings were observed when PSCI was defined by the Montreal Cognitive Assessment score.

High plasma phenylacetylglutamine levels were associated with increased odds of PSCI at 3 months, suggesting that plasma phenylacetylglutamine might be a potential predictive biomarker for PSCI among patients with ischemic stroke.