Tabriz University of Medical Sciences Journal of Cardiovascular and Thoracic Research 2008-5117 17 3 2025 09 28 Predictive model of neurocognitive functioning after acute coronary syndrome. A machine learning approach 181 187 10.34172/jcvtr.025.33340 EN Inês Moreira Miguel Peixoto Dulce Sousa Afonso Rocha Bruno Peixoto https://orcid.org/0000-0002-2427-6330 Journal Article 10.34172/jcvtr.025.33340 2024 08 24 2025 07 13 Introduction: The interplay between coronary disease and neurocognitive dysfunction remains unclear with several underlying factors likely contributing to this complex relationship. This study develops a predictive model using a machine learning approach to determine a predictive model of neurocognitive functioning in patients with acute coronary syndrome (ACS). Methods: Sixty-three patients, enrolled in the phase III cardiac rehabilitation program, underwent a neurocognitive assessment. To predict neurocognitive functioning a cross validated random forest model was used (RF_cv) due to its robustness to non-linear relationships and overfitting, and its successful application in prior disease prediction studies. Results: The RF_cv model showed an r-squared of 0.978, an RMSE of 0.6309 and a MAE value of 0.479. The top-ten predictors in the model were: HDL, Depression, Glucose, Glycated Hemoglobin, B-Type Natriuretic Peptide, BMI (Kg/m2), Waist-to-Hip Ratio, Cholesterol, Anxiety and Age. Conclusion: The variance in neurocognitive functioning is explained by a combination of biochemical indicators and body composition, reflecting classical cardiovascular risk factors and depression. The obtained RF-cv predictive model supports early identification of patients for tailored interventions.