Artificial intelligence as a “co-pilot” in phenotyping patients with arterial hypertension and chronic cerebral ischemia
Introduction. The use of artificial intelligence (AI) technologies as an auxiliary tool makes it possible to improve the phenotyping of elderly patients with arterial hypertension (AH) and chronic cerebral ischemia (CCI) and increases the effectiveness of therapy, taking into account individual characteristics. Objective: To evaluate the potential of AI technologies as an assistive tool (a “copilot”) for phenotyping elderly patients with AH and CCI, as well as to examine the clinical outcomes of sequential therapy with ethylmethylhydroxypyridine succinate (EMHPS – Mexidol and Mexidol 250 FORTE) in this group. Material and methods. A prospective cohort study included 1,235 participants over 60 years of age (median age 68 [64; 73] years; 57.3% women) with confirmed AH and CCI stages I–II. Stratified randomization allocated participants into two groups: the main group (n = 618) received sequential EMHPS therapy (intravenous infusion of 500 mg (10 ml) once a day for 14 days, followed by oral administration of 250 mg three times daily for 60 days) in addition to basic care, while the control group (n = 617) received basic therapy alone. For patient phenotyping, a machine learning algorithm (random forest with gradient boosting) integrated into a clinical decision support system was used. Cognitive status (MoCA, FAB, 10-Word Recall Test), levels of anxiety and depression (HADS), and asthenia (MFI-20) were assessed on days 1, 14, and 74. Results. The AI algorithm identified four phenotypes of patients with AH and CCI: “cerebrovascular” (32.4%), “dyscirculatory with predominant anxiety” (28.7%), “asthenic” (22.1%), and “cognitive” (16.8%). In the main group, by day 74, significant improvements were observed in cognitive function: MoCA increased by 3.2 points (p <0.001 vs control) and FAB by 4.1 points (p <0.001). HADS anxiety and depression scores decreased by 7.8 (p <0.001) and 3.4 points (p <0.01), respectively; MFI-20 asthenia score decreased by 28.6 points (p <0.01). The greatest therapeutic effect was observed in the “dyscirculatory with anxiety” and “cognitive” phenotypes. Conclusion. The use of AI as a “co-pilot” allows for the personalization of treatment in elderly patients with AH and CCI. The addition of EMHPS to baseline therapy improves cognitive outcomes, and reduces anxiety, depression, and asthenia, with the maximal benefit observed in specific clinical phenotypes.I.A. Zolotovskaya, D.V. Duplyakov, P.R. Shatskaia
Keywords
artificial intelligence
phenotyping
arterial hypertension
chronic cerebral ischemia
ethylmethylhydroxypyridine succinate (Mexidol)
cognitive impairment
anxiety
depression
References
- Iadecola C, Gottesman RF. Neurovascular and cognitive dysfunction in hypertension. Circ Res. 2019;124(7):1025–44.
PMID: 30920929. PMCID: PMC6527115. https://doi.org/10.1161/CIRCRESAHA.118.313260
- Osman A, Kanaan A, Azeroual S, Abubakr M, Jwayyed J, Bhutta R. Hypertension and cerebral small vessel disease: A review of the pathophysiology, progression, and prevention. Cureus. 2025;17(9):e92760.
PMID: 41122621. PMCID: PMC12536236. https://doi.org/10.7759/cureus.92760
- Walker KA, Sharrett AR, Wu A, Schneider ALC, Albert M, Lutsey PL, et al. Association of midlife to late-life blood pressure patterns with incident dementia. JAMA. 2019;322(6):535–45.
PMID: 31408138. PMCID: PMC6692677. https://doi.org/10.1001/jama.2019.10575
- Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, et al.; American Heart Association Stroke Council, Council on Epidemiology and Prevention, Council on Cardiovascular Nursing, Council on Cardiovascular Radiology and Intervention, and Council on Cardiovascular Surgery and Anesthesia. Vascular contributions to cognitive impairment and dementia: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42(9):2672–713.
PMID: 21778438. PMCID: PMC3778669. https://doi.org/10.1161/STR.0b013e3182299496
- Zhang H, Ma W, Zhou X, Zhao Z, Zhang R, Bai H, et al. Artificial intelligence in cerebrovascular disease management: A comprehensive review of risk prediction, diagnosis, therapeutic optimization, and clinical translation. Vasc Health Risk Manag. 2025;21:949–64.
PMID: 41312451. PMCID: PMC12649784. https://doi.org/10.2147/VHRM.S555592
- Roubenoff E, Simon M, Crowley M, James A, Gleeson M, Doddamani S, Kashyap N. Whole patient targeting highly predicts future stroke events: A risk stratification model for timely intervention in senior populations. Circulation. 2025;152(Suppl_3):A4349985.
https://doi.org/10.1161/circ.152.suppl_3.4349985
- Федин А.И., Захаров В.В., Танашян М.М., Чуканова Е.И., Маджидова Е.Н., Щепанкевич Л.А., Остроумова О.Д. Результаты международного многоцентрового рандомизированного двойного слепого плацебо-контролируемого исследования оценки эффективности и безопасности последовательной терапии пациентов с хронической ишемией мозга препаратами Мексидол и Мексидол ФОРТЕ 250 (исследование МЕМО). Журнал неврологии и психиатрии им. С.С. Корсакова. 2021;121(11):7–16. [Fedin AI, Zakharov VV, Tanashyan MM, Chukanova EI, Madzhidova EN, Shchepankevich LA, Ostroumova OD. Results of an international multicenter, randomized, double-blind, placebo-controlled study assessing the efficacy and safety of sequential therapy with Mexidol and Mexidol FORTE 250 in patients with chronic brain ischemia (MEMO). Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2021;121(11):7–16 (In Russ.)].
EDN: OBNTNH. https://doi.org/10.17116/jnevro20211211117
- Щепанкевич Л.А., Николаев Ю.А., Танеева Е.В., Первунинская М.А., Щепанкевич М.С. Эффективность и безопасность терапии лекарственными препаратами Мексидол и Мексидол ФОРТЕ 250 у пациентов с хронической ишемией головного мозга. Журнал неврологии и психиатрии им. С.С. Корсакова. 2021;121(10):32–37. [Shchepankevich LA, Nicolaev YuA, Taneeva EV, Pervuninskaya MA, Shchepankevich MS. The efficacy and safety study of Mexidol and Mexidol FORTE 250 in patients with chronic cerebral ischemia. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2021;121(10):32–37 (In Russ.)].
EDN: EQAASX. https://doi.org/10.17116/jnevro202112110132
- Михин В.П., Боровкова Н.Ю., Шулындин А.В. Возможности применения цитопротекторов в комплексной терапии хронической формы ишемической болезни сердца. Кардиология и сердечно-сосудистая хирургия. 2024;17(4):410–419. [Mikhin VP, Borovkova NYu, Shulyndin AV. Possibilities of using cytoprotectors in complex therapy of chronic coronary heart disease. Kardiologiya i serdechno-sosudistaya khirurgiya = Russian Journal of Cardiology and Cardiovascular Surgery. 2024;17(4):410–419 (In Russ.)].
EDN: EVLWLR. https://doi.org/10.17116/kardio202417041410
- Журавлева М.В., Прокофьев А.Б., Сереброва С.Ю., Васюкова Н.С., Демченкова Е.Ю., Архипов В.В. Эффективность и безопасность применения этилметилгидроксипиридина сукцината у пациентов с хронической ишемией головного мозга. Журнал неврологии и психиатрии им. С.С. Корсакова. 2020;120(6):119–124. [Zhuravleva MV, Prokofiev AB, Serebrova SYu, Vasyukova NS, Demchenkova EYu, Arkhipov VV. Efficacy and safety of ethylmethylhydroxypyridine succinate in patients with chronic cerebral ischemia. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2020;120(6):119–124 (In Russ., In Engl.)].
EDN: GNCITB. https://doi.org/10.17116/jnevro2020120061119
- Елисеева Л.Н., Карташова С.В. Мексидол® и Мексидол® ФОРТЕ 250 в рамках последовательной терапии когнитивных нарушений у коморбидных пациентов с патологией суставов на фоне артериальной гипертензии и ИБС. Терапия. 2020;6(6):202–211. [Eliseeva LN, Kartashova SV. Mexidol® and Mexidol® FORTE 250 in consecutive therapy of cognitive disorders in comorbid patients with joint pathology on the background of arterial hypertension and ischemic heart disease. Terapiya = Therapy. 2020;6(6):202–211 (In Russ.)].
EDN: GUAWZW. https://doi.org/10.18565/therapy.2020.6.202-211
- Антипенко Е.А., Шулындин А.В., Беляков К.М. Нейрометаболическая терапия умеренных когнитивных расстройств у пациентов с хронической ишемией головного мозга. Журнал неврологии и психиатрии им. С.С. Корсакова. 2024;124(3):42–51. [Antipenko EA, Shulyndin AV, Belyakov KM. Neurometabolic therapy of mild cognitive impairment in patients with chronic cerebral ischemia. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2024;124(3):42–51 (In Russ.)].
EDN: GCUELK. https://doi.org/10.17116/jnevro202412403142
- Белкин А.А., Белкин В.А., Васильченко И.Е., Пинчук Е.А. Результаты когортного одноцентрового рандомизированного исследования модулирующего эффекта препарата Мексидол в реабилитации пациентов, перенесших острую церебральную недостаточность. Журнал неврологии и психиатрии им. С.С. Корсакова. 2024;124(4):108–117. [Belkin AA, Belkin VA, Vasilchenko IE, Pinchuk EA. Results of a cohort single-center randomized study of the modulating effect of the drug Mexidol in the rehabilitation of patients who suffered acute cerebral insufficiency. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2024;124(4):108–117 (In Russ.)].
EDN: CVLEDT. https://doi.org/10.17116/jnevro2024124041108
- Пугачева Е.Л. Эффективность препарата Мексидол у пациентов с неврологическими осложнениями сахарного диабета 2-го типа. Журнал неврологии и психиатрии им. С.С. Корсакова. 2022;122(5):84–89. [Pugacheva EL. Efficacy of Mexidol in patients with type 2 diabetes mellitus with neurological complications. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2022;122(5):84–89 (In Russ.)].
EDN: UQRBPB. https://doi.org/10.17116/jnevro202212205184
- Журавлева М.В., Камчатнов П.Р., Васюкова Н.С., Архипов В.В., Кузнецова Е.В., Каменева Т.Р., Сереброва С.Ю. Результаты клинических исследований эффективности и безопасности применения препаратов этилметилгидроксипиридина сукцината у пациентов с хронической ишемией головного мозга. Журнал неврологии и психиатрии им. С.С. Корсакова. 2022;122(11):29–39. [Zhuravleva MV, Kamchatnov PR, Vasyukova NS, Arkhipov VV, Kuznetsova EV, Kameneva TR, Serebrova SYu. Results of clinical studies of the efficacy and safety of the use of ethylmethylhydroxypyridine succinate in patients with chronic cerebral ischemia. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2022;122(11):29–39 (In Russ.)].
EDN: UEUCAF. https://doi.org/10.17116/jnevro202212211129
- Шишкова В.Н., Приходько В.А., Оковитый С.В. Выбор современного нейропротекторного препарата как базовая стратегия в терапии хронических цереброваскулярных заболеваний. Медицинский совет. 2023;(10):41–49. [Shishkova VN, Prikhodko VA, Okovityi SV. The choice of a modern neuroprotective drug as a basic strategy in the treatment of chronic cerebrovascular diseases. Meditsinskiy sovet = Medical Council. 2023;17(10):41–49 (In Russ.)].
EDN: TSASBQ. https://doi.org/10.21518/ms2023-232
- Михин В.П., Костина Н.Л., Николенко Т.А., Савельева В.В., Чернятина М.А. Возможности применения этилметилгидроксипиридина сукцината в комплексной терапии артериальной гипертензии. Кардиология и сердечно-сосудистая хирургия. 2024;17(5):572–580. [Mikhin VP, Kostina NL, Nikolenko TA, Savelyeva VV, Chernyatina MA. The possibilities of Mexidol in the complex therapy of arterial hypertension. Kardiologiya i serdechno-sosudistaya khirurgiya = Russian Journal of Cardiology and Cardiovascular Surgery. 2024;17(5):572–580 (In Russ.)].
EDN: ABPWVS. https://doi.org/10.17116/kardio202417051572
- Катаева Н.Г., Замощина Т.А., Светлик М.В. Эффективность и безопасность препарата Мексидол Форте 250 при последовательной терапии пациентов с хронической ишемией мозга. Журнал неврологии и психиатрии им. С.С. Корсакова. 2020;120(11):59–63. [Kataeva NG, Zamoshchina TA, Svetlik MV. Effectiveness and safety of mexidol forte 250 in the sequential therapy in patients with chronicischemia. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2020;120(11):59–63 (In Russ.)].
EDN: OZAFFL. https://doi.org/10.17116/jnevro202012011159
- Кочетков А.И., Шаталова Н.А., Клепикова М.В., Филиппова Т.В., Остроумова О.Д. К вопросу о доказательной базе нейропротектерной терапии: фокус на этилметилгидроксипиридина сукцинат. Терапия. 2023;9(8):162–172. [Kochetkov AI, Shatalova NA, Klepikova MV, Filippova TV, Ostroumova OD. More on the neuroprotectory therapy evidential base: Focus at ethylmethylhydroxypyridine succinate. Terapiya = Therapy. 2023;9(8):162–172 (In Russ.)].
EDN: EQQUCV. https://doi.org/10.18565/therapy.2023.8.162-172
- Аксенова А.В., Ощепкова Е.В., Чазова И.Е. Антигипертензивная терапия у коморбидных больных артериальной гипертонией в условиях реальной клинической практики (по данным национального регистра артериальной гипертонии, 2019–2022 гг.). Терапевтический архив. 2024;96(9):860–871. [Aksenova AV, Oschepkova EV, Chazova IE. Antihypertensive therapy in patients with arterial hypertension and concomitant diseases in real clinical practice (according to the National Registry of Arterial Hypertension, 2019–2022). Terapevticheskiy arkhiv = Therapeutic Archive. 2024;96(9):860–871 (In Russ.)].
EDN: FIATCB. https://doi.org/10.26442/00403660.2024.09.202848
About the Authors
Irina A. Zolotovskaya, MD, Dr. Sci. (Medicine), head of the Department of scientific and innovative technologies in healthcare, professor of the Department of hospital therapy with courses in hematology and transfusiology, Samara State Medical University, Samara, Russian Federation.E-mail: i.a.zolotovskaya@samsmu.ru
ORCID: https://orcid.org/0009-0006-8541-9100
Dmitry V. Duplyakov, MD, Dr. Sci. (Medicine), professor, head of the Department of propaedeutics of internal diseases with a course in cardiology, Samara State Medical University, Samara, Russian Federation.
E-mail: d.v.duplyakov@samsmu.ru
ORCID: https://orcid.org/0000-0002-6453-2976
Polina R. Shatskaia, MD, assistant at the Department of propaedeutics of internal diseases with a course in cardiology, Samara State Medical University, Samara, Russian Federation.
Е-mail: polya.sha98@gmail.com
ORCID: https://orcid.org/0000-0001-5183-1208
Similar Articles
