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Introduction: the hypothesis of a relation between the biochemical markers and cognitive variables is based on the increased blood levels of certain proteins are indicators of neural damage and the cognitive processes depends on the integrity of neural networks distributed in the whole brain. Objective: to determinate the association between serum markers neuron specific enolase (NSE) and S100β protein with the executive functions in hypertensive patients. Methods: 43 hypertensive patients (22 women and 21 men) were included. Mean age was 63.4 ± 12.4 years, 17 patients had suffered ischemic stroke and 26 patients had not. Serum markers were determined and cognitive processes (sustained attention, operative visual memory and executive functions) were evaluated. Mann- Whitney U-test was used to determine the relationship between the levels of both serums markers and the presence of stroke. A general linear model was employed to determine the association between the cognitive variables and serum concentrations of both enzymes. Results: The mean of serum levels of NSE and S100β were 13.4 (±8.9) μg/L and 137.2 (±111.1) ng/L respectively. Patients with stroke history tended to have higher levels of both enzymes than those without stroke, but not statistically significant (NSE: Z = -1.04 p= 0.29 and S100β: Z= -1.56 p= 0.12). A multivariate analysis showed that higher serum levels of NSE (p=0.005 r=0.47) and S100β protein (p=0.02 r =0.42) were indicative of a delayed reaction time to correct responses in Stroop´s test. [ABSTRACT FROM AUTHOR]