Background: Arterial hypertension (AH) is one of the main factors causing a high risk of cardiovascular complications and mortality. The existence of a relationship between high blood pressure (BP) and the risk of developing central nervous system pathology, primarily stroke, and cognitive impairment, has been shown. The purpose of this study was a comparative assessment of the effect of 12-month antihypertensive therapy (AHT) with the inclusion of nitrendipine (NIT) or amlodipine (AML) on cognitive functions (CF) in hypertensive patients. Methods and Results: The study included 111 patients of both genders aged 30-75 years with AH Grades 1-3 (ESC/ESH, 2018). All patients underwent the following examinations: assessment of traditional risk factors, physical examination, clinical and biochemical laboratory methods, 12-lead ECG, echocardiography, pulse contour analysis, and 24-hour ambulatory blood pressure monitoring, neuropsychological tests (Mini-Cog test, Montreal Cognitive Assessment (MoCA) test, Hospital Anxiety and Depression Scale (HADS), and self-assessment questionnaire for memory, attention, thinking, ability to cope with one's affairs, and ability to make decisions). After the screening stage, all patients were discontinued from previous therapy and assigned to the 2 regimes of AHT. Group 1 included 58 AH patients who received NIT as monotherapy or as part of combination AHT; Group 2 included 53 patients who received AML as monotherapy or as part of combination AHT. Correlation analysis between the parameters of DBPP and the MoCA test revealed a weak but statistically significant negative correlation between the total MoCA score and the average 24-h SBP (rs=-0.33, P=0.015). In addition, there was a weak but statistically significant negative correlation between the total MoCA score and the daytime SBP variability and daytime DBP variability (rs=-0.40 and rs=-0.35, respectively, P=0.000 in both cases). A weak but statistically significant negative correlation was found between the total Mini-Cog score and PWV and PPc (rs=-0.24, P=0.01 and rs=-0.27, P=0.007, respectively). Analysis of the office BP indicators showed high antihypertensive efficacy of 12-month therapy in both groups, regardless of the therapy regimens. A comparative analysis of the effect of AHT with the inclusion of NIT or AML on CF in AH patients showed the advantages of combined AHT with the inclusion of NIT. Amlodipine treatment did not significantly affect any test score. Thus, in Group 1, after 12 months of therapy, there was an increase in the total Mini-Cog score from 3.8±1.08 points to 4.55±0.75 points (P<0.001), while in Group 2, there was a non-significant decrease in this score from 4.26±0.98 points to 3.92±0.95 points (P>0.05). There was also an increase in the total MoCA score in Group 1 from 23.3±2.8 points to 25.08±2.6 points (P<0.001), while in Group 2, there was a non-significant decrease in this score from 24.06±2.73 points to 23.07±2.7 points (P>0.05). It should be noted that only in Group 1 did we find a significant improvement in CF, such as abstraction, delayed recall, memory, and attention, as well as a significant improvement in work-coping and decision-making. In Group 1, the HADS Depression score decreased from 4.6±3.7 points to 3.32±2.95 points (P<0.05), HADS Anxiety score decreased from 7.01±5.37 points to 4.95±3.75 points (P<0.02). At the same time, in Group 2, in contrast, the HADS Depression score and the HADS Anxiety score did not significantly change. Conclusion: A weak but statistically significant negative correlation was found between the total MoCA score and the daytime SBP/DBP variability in AH patients. A weak but statistically significant negative correlation was found between the total Mini-Cog score and pulse wave velocity and central pulse pressure. A pronounced antihypertensive efficacy of 12-month combination therapy was noted, with the inclusion of both NIT and AML. The NIT-based treatment contributed to a significant increase in the total Mini-Cog score and the total MoCA score and a substantial improvement in CF. Abstraction, delayed recall, memory, attention, work-coping, and decision-making significantly improved, compared to AML-based treatment. The presented data allow a differentiated approach to tactics for treating AH patients with severe cognitive impairment.