Association of acute-phase plasma pTau217 levels with long-term post-stroke cognitive impairment

Mónica Macías, Elena Escriche, María Molina, Inhar Esnaola, Adrián Jiménez, Sara Razquin-Sola, Miren Roldán, Amaya Urdánoz‐Casado, Nuria Sobrino, Celia Fernández, Idoia Rubio, Dagoberto Aspra, Carlota Jáuregui, Roberto Muñóz, María Herrera, Maite Mendióroz

Background Post-stroke cognitive impairment (PSCI) is a common complication affecting stroke survivors, yet early biomarkers for risk stratification remain scarce. Plasma pTau217 has emerged as a specific biomarker for Alzheimer’s disease pathology. This study explores whether acute-phase pTau217 levels are associated with PSCI. Methods We conducted a nested case-control study including 48 patients who developed PSCI within 5 years and 48 age and sex-matched patients as controls without cognitive decline. Plasma pTau217 was measured within 24 h after stroke onset using SIMOA. Statistical analysis included multivariable logistic regression, dose-response assessment via quartile stratification, and ROC curves. Results Plasma pTau217 levels were significantly higher in PSCI cases than controls [0.313 (0.196–0.562) vs. 0.203 (0.126–0.343) pg/mL; p- value < 0.01]. Notably, pTau217 levels were not correlated with stroke severity (NIHSS at baseline) or atrial fibrillation, suggesting that pTau217 may reflect baseline neurobiological vulnerability. In multivariable models, ln-pTau217 levels were independently associated with PSCI risk (OR = 2.28; 95%CI = 1.19–4.37; p -value < 0.05). A significant linear dose-response relationship was observed, with PSCI risk increasing from 29.2% in the lowest quartile to 64.0% in the highest ( p- value for trend < 0.05). The biomarker alone showed a significant discriminative capacity for clinically documented PSCI (AUC = 0.660; 95%CI = 0.552–0.768; p -value < 0.01). Furthermore, sex-stratified analysis revealed that the association was primarily driven by females. Conclusion Higher acute-phase pTau217 levels were associated with an increased likelihood of clinically documented cognitive impairment during follow-up. These exploratory findings suggest that acute-phase pTau217 may be associated with long-term cognitive outcomes after stroke, although larger prospective studies, integrating additional biomarkers with standardized neuropsychological assessment are needed.