medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2020-8-72-80medsovet-5682Research ArticleКОГНИТИВНЫЕ РАССТРОЙСТВАCOGNITIVE DISRODERSАртериальная гипертензия и когнитивные нарушения: мультимодальный подход к ведению больных и возможности ницерголинаArterial hypertension and cognitive impairment: multimodal approach for patient care and nicergoline usehttps://orcid.org/0000-0002-0795-8225ОстроумоваО. Д.OstroumovaO. D.

Остроумова Ольга Дмитриевна,д.м.н., профессор, заведующая кафедрой терапии и полиморбидной патологии; профессор кафедры клинической фармакологии и пропедевтики внутренних болезней института клинической медицины им. Н.В. Склифосовского

125993, Россия, Москва, ул. Баррикадная, д. 2/1, стр. 1

119991, Россия, Москва, ул. Трубецкая, д. 8, стр. 2

Olga D. Ostroumova,Dr. of Sci. (Med), Professor, Head of the department of general medicine and polymorbid pathology; professor of the department of Department of Clinical Pharmacology and Propaedeutics of Internal Diseases Federal State Autonomous Educational Institution of Higher Education

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993, Russia

8, Bldg. 2, Trubetskaya St., Moscow, 119991, Russia

ostroumova.olga@mail.ruhttps://orcid.org/0000-0003-1499-247XОстроумоваТ. М.OstroumovaT. M.

Остроумова Татьяна Максимовна, к.м.н., ассистент кафедры нервных болезней и нейрохирургии института клинической медицины им. Н.В. Склифосовского

119991, Россия, Москва, ул. Трубецкая, д. 8, стр. 2

Tatiana M. Ostroumova, Cand. of Sci. (Med.), assistant professor of department of neurology and neurosurgery

8, Bldg. 2, Trubetskaya St., Moscow, 119991, Russia

t.ostroumova3@gmail.comhttps://orcid.org/0000-0002-8941-7018ДзамиховК. К.DzamikhovK. K.

Дзамихов Кантемир Каральбиевич, аспирант кафедры терапии и полиморбидной патологии

125993, Россия, Москва, ул. Баррикадная, д. 2/1, стр. 1

Kantemir K. Dzamikhov, postgraduate student at the department of general medicine and polymorbid pathology

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993, Russia

dzamihov.93@mail.ruРоссийская медицинская академия непрерывного профессионального образования; Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)РоссияRussian Medical Academy of Continuous Professional Education; First Moscow State Medical University named after I.M. Sechenov (Sechenov University)Russian FederationПервый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)РоссияFirst Moscow State Medical University named after I.M. Sechenov (Sechenov University)Russian FederationРоссийская медицинская академия непрерывного профессионального образованияРоссияRussian Medical Academy of Continuous Professional EducationRussian Federation202014072020087280Copyright © Остроумова О.Д., Остроумова Т.М., Дзамихов К.К., 20202020Остроумова О.Д., Остроумова Т.М., Дзамихов К.К.Ostroumova O.D., Ostroumova T.M., Dzamikhov K.K.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/5682

Артериальная гипертензия (АГ) – один из главных модифицируемых факторов риска развития когнитивных нарушений (КН). Наиболее часто у пациентов с АГ, вне зависимости от возраста, страдают управляющие функции. Патофизиологические механизмы взаимосвязи АГ и КН реализуются через влияние повышенного артериального давления на крупные и малые артерии головного мозга. Поражение крупных церебральных артерий при АГ приводит к их локальным окклюзиям, локальному ремоделированию и увеличению жесткости сосудистой стенки. АГ способствует дегенеративному изменению сосудистой стенки артерий малого калибра: липогиалинозу и фибриноидному некрозу; из-за недостаточного количества анастомозов и коллатералей их дисфункция и/или окклюзия ведет к повреждению белого вещества головного мозга. Подход к ведению пациентов с АГ и КН должен быть мультимодальным и включать в себя терапию основного заболевания (антигипертензивные средства, по показаниям – антитромботические препараты и статины), симптоматическую (например, противодементные препараты) и патогенетическую (препараты, направленные на улучшение микроциркуляции, нейрометаболические препараты) терапию. В настоящее время доказана способность антигипертензивной терапии снижать риск развития новых случаев деменции, влияние отдельных классов препаратов требует дальнейшего изучения. В 30 странах для коррекции КН достаточно широко применяется препарат ницерголин – полусинтетическое производное алкалоида спорыньи. Влияние ницерголина на КН при АГ обусловлено мультимодальным действием препарата: он увеличивает метаболизм глюкозы в головном мозге, стимулирует холинергическую передачу, увеличивает церебральный кровоток, оказывает влияние на микроциркуляцию, уменьшает жесткость сосудистой стенки, обладает α1-адреноблокирующими свойствами. Препарат показал свою эффективность в коррекции КН при АГ в ряде исследований и метаанализах. Данные доказательной медицины демонстрируют также хорошую переносимость лечения ницерголином.

Arterial hypertension is one of the main modifiable risk factor for cognitive impairement (CI). Most frequently executive dysfunction is seen independent of age. Pathophysiological mechanisms linking hypertension and CI include the impact of increased blood pressure on large and small cerebral arteries. Large arteries dysfunction leads to occlusion, remodeling and arterial stiffness. Hypertension also causes small arteries dysfunction: lipohyalinosis and fibrinoid necrosis and due to insufficient amount of anastomosis and collaterals can lead to white matter damage. Treatment approach for patients with hypertension and CI should be multimodal and include treatment of the main cause of CI (antihypertensive therapy, statins and antithrombotics if necessary), symptomatic therapy (e.g. anti-dementia medications) and pathogenic treatment drugs that influence microcirculation, neuromethabolic therapy. Antihypertensive therapy is known to decrease dementia incidence, but the interclass differences remain unclear. Nicergoline (the ergot alkaloid derivative) is used in 30 countries to treat CI. Nicergoline improves CI due to its multidoi modal action, which includes increasing glucose metabolism in the brain, stimulation of cholinergic neurotransmission, increasing cerebral blood flow, influencing microcirculation due to decreasing arterial stiffness, blocking α1-adrenergic receptors. Nicergoline is effective in treating hypertensive patients with CI according to the data of a number of studies and meta-analysis. Evidencebased data also shows good tolerance profile of nicergoline.

артериальная гипертензиякогнитивные функциикогнитивные нарушениядеменцияницерголинarterial hypertensioncognitive functionscognitive impairmentdementianicergolineReferencesЕрина А.М., Ротарь О.П., Солнцев В.Н., Шальнова С.А., Деев А.Д., Баранова Е.И. и др. Эпидемиология артериальной гипертензии в Российской Федерации – важность выбора критериев диагностики. Кардиология. 2019;59(6):5–11. doi: 10.18087/cardio.2019.6.2595.Erina A.M., Rotar O.P., Solntsev V.N., Shalnova S.A., Deev A.D., Baranova E.I. et al. Epidemiology of Arterial Hypertension in Russian Federation – Importance of Choice of Criteria of Diagnosis. Kardiologiia. 2019;59(6):5–11. (In Russ.) doi: 10.18087/cardio.2019.6.2595.Williams B., Mancia G., Spiering W., Rosei E.A., Azizi M., Burnier M. et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021–3104. doi: 10.1093/eurheartj/ehy339.Williams B., Mancia G., Spiering W., Rosei E.A., Azizi M., Burnier M. et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021–3104. doi: 10.1093/eurheartj/ehy339.Lennon M.J., Makkar S.R., Crawford J.D., Sachdev P.S. Midlife hypertension and Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis. 2019;71(1):307–316. doi: 10.3233/JAD-190474.Lennon M.J., Makkar S.R., Crawford J.D., Sachdev P.S. Midlife hypertension and Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis. 2019;71(1):307–316. doi: 10.3233/JAD-190474.Gottesman R.F., Rawlings A.M., Sharrett A.R., Albert M., Alonso A., Bandeen-Roche K. et al. Impact of differential attrition on the association of education with cognitive change over 20 years of follow-up: the ARIC neurocognitive study. Am J Epidemiol. 2014;179(8):956–966. doi: 10.1093/aje/kwu020.Gottesman R.F., Rawlings A.M., Sharrett A.R., Albert M., Alonso A., Bandeen- Roche K. et al. Impact of differential attrition on the association of education with cognitive change over 20 years of follow-up: the ARIC neurocognitive study. Am J Epidemiol. 2014;179(8):956–966. doi: 10.1093/aje/kwu020.Goldstein F.C., Levey A.I., Steenland N.K. High blood pressure and cognitive decline in mild cognitive impairment. J Am Geriatr Soc. 2013;61(1):67–73. doi: 10.1111/jgs.12067.Goldstein F.C., Levey A.I., Steenland N.K. High blood pressure and cognitive decline in mild cognitive impairment. J Am Geriatr Soc. 2013;61(1):67–73. doi: 10.1111/jgs.12067.Launer L.J., Ross G.W., Petrovitch H., Masaki K., Foley D., White L.R., Havlik R.J. Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol Aging. 2000;21(1):49–55. doi: 10.1016/s0197-4580(00)00096-8.Launer L.J., Ross G.W., Petrovitch H., Masaki K., Foley D., White L.R., Havlik R.J. Midlife blood pressure and dementia: the Honolulu-Asia aging study. Neurobiol Aging. 2000;21(1):49–55. doi: 10.1016/s0197-4580(00)00096-8.Shah N.S., Vidal J.S., Masaki K., Petrovitch H., Ross G.W., Tilley C. et al. Midlife blood pressure, plasma β-amyloid, and the risk for Alzheimer disease: the Honolulu Asia Aging Study. Hypertension. 2012;59(4):780–786. doi: 10.1161/hypertensionaha.111.178962.Shah N.S., Vidal J.S., Masaki K., Petrovitch H., Ross G.W., Tilley C. et al. Midlife blood pressure, plasma β-amyloid, and the risk for Alzheimer disease: the Honolulu Asia Aging Study. Hypertension. 2012;59(4):780–786. doi: 10.1161/hypertensionaha.111.178962.Glynn R.J., Beckett L.A., Hebert L.E., Morris M.C., Scherr P.A., Evans D.A. Current and remote blood pressure and cognitive decline. JAMA. 1999;281(5):438–445. doi: 10.1001/jama.281.5.438.Glynn R.J., Beckett L.A., Hebert L.E., Morris M.C., Scherr P.A., Evans D.A. Current and remote blood pressure and cognitive decline. JAMA. 1999;281(5):438–445. doi: 10.1001/jama.281.5.438.Ruitenberg A., Skoog I., Ott A., Aevarsson O., Witteman J.C., Lernfelt B. et al. Blood pressure and risk of dementia: results from the Rotterdam study and the Gothenburg H-70 Study. Dement Geriatr Cogn Disord. 2001;12:33–39. doi: 10.1159/000051233.Ruitenberg A., Skoog I., Ott A., Aevarsson O., Witteman J.C., Lernfelt B. et al. Blood pressure and risk of dementia: results from the Rotterdam study and the Gothenburg H-70 Study. Dement Geriatr Cogn Disord. 2001;12:33–39. doi: 10.1159/000051233.Streit S., Poortvliet R.K.E., Elzen W.P.J.D., Blom J.W., Gussekloo J. Systolic blood pressure and cognitive decline in older adults with hypertension. Ann Fam Med. 2019;17(2):100–107. doi: 10.1370/afm.2367.Streit S., Poortvliet R.K.E., Elzen W.P.J.D., Blom J.W., Gussekloo J. Systolic blood pressure and cognitive decline in older adults with hypertension. Ann Fam Med. 2019;17(2):100–107. doi: 10.1370/afm.2367.Ninomiya T., Ohara T., Hirakawa Y., Yoshida D., Doi Y., Hata J. et al. Midlife and late-life blood pressure and dementia in Japanese elderly: the Hisayama study. Hypertension. 2011;58(1):22–28. doi: 10.1161/HYPERTENSIONAHA.110.163055.Ninomiya T., Ohara T., Hirakawa Y., Yoshida D., Doi Y., Hata J. et al. Midlife and late-life blood pressure and dementia in Japanese elderly: the Hisayama study. Hypertension. 2011;58(1):22–28. doi: 10.1161/HYPERTENSIONAHA.110.163055.Yamada M., Kasagi F., Sasaki H., Masunari N., Mimori Y., Suzuki G. Association between dementia and midlife risk factors: the Radiation Effects Research Foundation Adult Health Study. J Am Geriatr Soc. 2003;51:410–414. doi: 10.1046/j.1532-5415.2003.51117.x.Yamada M., Kasagi F., Sasaki H., Masunari N., Mimori Y., Suzuki G. Association between dementia and midlife risk factors: the Radiation Effects Research Foundation Adult Health Study. J Am Geriatr Soc. 2003;51:410–414. doi: 10.1046/j.1532-5415.2003.51117.x.Kivipelto M., Helkala E.L., Laakso M.P., Hänninen T., Hallikainen M., Alhainen K. et al. Midlife vascular risk factors and Alzheimer’s disease in later life: longitudinal, population based study. BMJ. 2001;322:1447–1451. doi: 10.1136/bmj.322.7300.1447.Kivipelto M., Helkala E.L., Laakso M.P., Hänninen T., Hallikainen M., Alhainen K. et al. Midlife vascular risk factors and Alzheimer’s disease in later life: longitudinal, population based study. BMJ. 2001;322:1447–1451. doi: 10.1136/bmj.322.7300.1447.Swan G.E., DeCarli C., Miller B.L., Reed T., Wolf P.A., Jack L.M., Carmelli D. Association of midlife blood pressure to late-life cognitive decline and brain morphology. Neurology. 1998;51(4):986–993. doi: 10.1212/WNL.51.4.986.Swan G.E., DeCarli C., Miller B.L., Reed T., Wolf P.A., Jack L.M., Carmelli D. Association of midlife blood pressure to late-life cognitive decline and brain morphology. Neurology. 1998;51(4):986–993. doi: 10.1212/WNL.51.4.986.Sierra C., De La Sierra A., Salamero M., Sobrino J., Gómez-Angelats E., Coca A. Silent cerebral white matter lesions and cognitive function in middle-aged essential hypertensive patients. Am J Hypertens. 2004;17(6):529–534. doi: 10.1016/j.amjhyper.2004.02.014.Sierra C., De La Sierra A., Salamero M., Sobrino J., Gómez-Angelats E., Coca A. Silent cerebral white matter lesions and cognitive function in middle-aged essential hypertensive patients. Am J Hypertens. 2004;17(6):529–534. doi: 10.1016/j.amjhyper.2004.02.014.Gottesman R.F., Coresh J., Catellier D.J., Sharrett A.R., Rose K.M., Coker L.H. et al. Blood pressure and white-matter disease progression in a biethnic cohort: Atherosclerosis Risk in Communities (ARIC) study. Stroke. 2010;41(1):3–8. doi: 10.1161/STROKEAHA.109.566992.Gottesman R.F., Coresh J., Catellier D.J., Sharrett A.R., Rose K.M., Coker L.H. et al. Blood pressure and white-matter disease progression in a biethnic cohort: Atherosclerosis Risk in Communities (ARIC) study. Stroke. 2010;41(1):3–8. doi: 10.1161/STROKEAHA.109.566992.Парфенов В.А., Захаров В.В., Преображенская И.С. Когнитивные расстройства. М.: Ремедиум; 2014. 182 с.Parfenov V.A., Zakharov V.V., Preobrazhenskaya I.S. Cognitive impairment. Moscow: Remedium; 2014. 182 p. (In Russ.)Hu X., De Silva T.M., Chen J., Faraci F.M. Cerebral vascular disease and neurovascular injury in ischemic stroke. Circ Res. 2017;120(3):449–471. doi: 10.1161/CIRCRESAHA.116.308427.Hu X., De Silva T.M., Chen J., Faraci F.M. Cerebral vascular disease and neurovascular injury in ischemic stroke. Circ Res. 2017;120(3):449–471. doi: 10.1161/CIRCRESAHA.116.308427.Kaess B.M., Rong J., Larson M.G., Hamburg N.M., Vita J.A., Levy D. et al. Aortic stiffness, blood pressure progression, and incident hypertension. JAMA. 2012;308(9):875–881. doi: 10.1001/2012.jama.10503.Kaess B.M., Rong J., Larson M.G., Hamburg N.M., Vita J.A., Levy D. et al. Aortic stiffness, blood pressure progression, and incident hypertension. JAMA. 2012;308(9):875–881. doi: 10.1001/2012.jama.10503.Jefferson A.L., Cambronero F.E., Liu D., Moore E.E., Neal J.E., Terry J.G. et al. Higher aortic stiffness is related to lower cerebral blood flow and preserved cerebrovascular reactivity in older adults. Circulation. 2018;138(18):1951–1962. doi: 10.1161/CIRCULATIONAHA.118.032410.Jefferson A.L., Cambronero F.E., Liu D., Moore E.E., Neal J.E., Terry J.G. et al. Higher aortic stiffness is related to lower cerebral blood flow and preserved cerebrovascular reactivity in older adults. Circulation. 2018;138(18):1951–1962. doi: 10.1161/CIRCULATIONAHA.118.032410.Schnerr R.S., Jansen J.F.A., Uludag K., Hofman P.A.M., Wildberger J.E., van Oostenbrugge R.J., Backes W.H. Pulsatility of lenticulostriate arteries assessed by 7 tesla flow MRI-measurement, reproducibility, and applicability to aging effect. Front Physiol. 2017;8:961. doi: 10.3389/fphys.2017.00961.Schnerr R.S., Jansen J.F.A., Uludag K., Hofman P.A.M., Wildberger J.E., van Oostenbrugge R.J., Backes W.H. Pulsatility of lenticulostriate arteries assessed by 7 tesla flow MRI-measurement, reproducibility, and applicability to aging effect. Front Physiol. 2017;8:961. doi: 10.3389/fphys.2017.00961.Iadecola C. The pathobiology of vascular dementia. Neuron. 2013;80(4):844–866. doi: 10.1016/j.neuron.2013.10.008.Iadecola C. The pathobiology of vascular dementia. Neuron. 2013;80(4):844–866. doi: 10.1016/j.neuron.2013.10.008.Debette S., Markus H.S. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ. 2010;341:c3666. doi: 10.1136/bmj.c3666.Debette S., Markus H.S. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ. 2010;341:c3666. doi: 10.1136/bmj.c3666.van Dijk E.J., Breteler M.M., Schmidt R., Berger K., Nilsson L.G., Oudkerk M. et al. The association between blood pressure, hypertension, and cerebral white matter lesions: cardiovascular determinants of dementia study. Hypertension. 2004;44(5):625–630. doi: 10.1161/01.HYP.0000145857.98904.20.van Dijk E.J., Breteler M.M., Schmidt R., Berger K., Nilsson L.G., Oudkerk M. et al. The association between blood pressure, hypertension, and cerebral white matter lesions: cardiovascular determinants of dementia study. Hypertension. 2004;44(5):625–630. doi: 10.1161/01.HYP.0000145857.98904.20.Sabayan B., van Vliet P., de Ruijter W., Gussekloo J., de Craen A.J., Westendorp R.G. High blood pressure, physical and cognitive function, and risk of stroke in the oldest old: the Leiden 85-plus Study. Stroke. 2013;44(1):15–20. doi: 10.1161/STROKEAHA.112.663062.Sabayan B., van Vliet P., de Ruijter W., Gussekloo J., de Craen A.J., Westendorp R.G. High blood pressure, physical and cognitive function, and risk of stroke in the oldest old: the Leiden 85-plus Study. Stroke. 2013;44(1):15–20. doi: 10.1161/STROKEAHA.112.663062.Chen Y., Wang A., Tang J., Wei D., Li P., Chen K. et al. Association of white matter integrity and cognitive functions in patients with subcortical silent lacunar infarcts. Stroke. 2015;46(4):1123–1126. doi: 10.1161/Chen Y., Wang A., Tang J., Wei D., Li P., Chen K. et al. Association of white matter integrity and cognitive functions in patients with subcortical silent lacunar infarcts. Stroke. 2015;46(4):1123–1126. doi: 10.1161/STROKEAHA.115.008998.STROKEAHA.115.008998.Brown R., Benveniste H., Black S.E., Charpak S., Dichgans M., Joutel A. et al. Understanding the role of the perivascular space in cerebral small vessel disease. Cardiovasc Res. 2018;114(11):1462–1473. doi: 10.1093/cvr/cvy113.Brown R., Benveniste H., Black S.E., Charpak S., Dichgans M., Joutel A. et al. Understanding the role of the perivascular space in cerebral small vessel disease. Cardiovasc Res. 2018;114(11):1462–1473. doi: 10.1093/cvr/cvy113.Passiak B.S., Liu D., Kresge H.A., Cambronero F.E., Pechman K.R., Osborn K.E. et al. Perivascular spaces contribute to cognition beyond other small vessel disease markers. Neurology. 2019;92(12):e1309–e1321. doi: 10.1212/WNL.0000000000007124.Passiak B.S., Liu D., Kresge H.A., Cambronero F.E., Pechman K.R., Osborn K.E. et al. Perivascular spaces contribute to cognition beyond other small vessel disease markers. Neurology. 2019;92(12):e1309–e1321.doi: 10.1212/WNL.0000000000007124.Vakhnina N.V. Cognitive impairment in arterial hypertension. Meditsinskiy sovet = Medical Council. 2015;(5):34–39. (In Russ.) doi: 10.21518/2079-701X-2015-5-34-39.Вахнина Н.В. Когнитивные нарушения при артериальной гипертензии. Медицинский совет. 2015;(5):34–39. doi: 10.21518/2079-701X-2015-5-34-39.Gupta R., Solanki R.K., Pathak V. Blood pressure is associated with cognitive impairment in young hypertensives. World J Biol Psychiatry. 2008;9(1):43–50. doi: 10.1080/15622970601187784.Gupta R., Solanki R.K., Pathak V. Blood pressure is associated with cognitive impairment in young hypertensives. World J Biol Psychiatry. 2008;9(1):43–50. doi: 10.1080/15622970601187784.Yeung S.E., Thornton W.L. Age-related effects of blood pressure on everyday cognitive function in community-dwelling women. Aging Neuropsychol Cogn. 2011;18(6):733–755. doi: 10.1080/13825585.2011.609882.Yeung S.E., Thornton W.L. Age-related effects of blood pressure on everyday cognitive function in community-dwelling women. Aging Neuropsychol Cogn. 2011;18(6):733–755. doi: 10.1080/13825585.2011.609882.Goldstein F.C., Hajjar I.M., Dunn C.B., Levey A.I., Wharton W. The relationship between cognitive functioning and the jnc-8 guidelines for hypertension in older adults. J Gerontol: Series A. 2017;72(1):121–126. doi: 10.1093/gerona/glw181.Goldstein F.C., Hajjar I.M., Dunn C.B., Levey A.I., Wharton W. The relationship between cognitive functioning and the jnc-8 guidelines for hypertension in older adults. J Gerontol: Series A. 2017;72(1):121–126. doi: 10.1093/gerona/glw181.Yasar S., Ko J.Y., Nothelle S., Mielke M.M., Carlson M.C. Evaluation of the effect of systolic blood pressure and pulse pressure on cognitive function: the Women’s Health and Aging Study II. PLoS One. 2011;6(12):e27976. doi: 10.1371/journal.pone.0027976.Yasar S., Ko J.Y., Nothelle S., Mielke M.M., Carlson M.C. Evaluation of the effect of systolic blood pressure and pulse pressure on cognitive function: the Women’s Health and Aging Study II. PLoS One. 2011;6(12):e27976. doi: 10.1371/journal.pone.0027976.Alipour H., Goldust M. The association between blood pressure components and cognitive functions and cognitive reserve. Clin Exp Hypertens. 2016;38(1):95–99. doi: 10.3109/10641963.2015.1047946.Alipour H., Goldust M. The association between blood pressure components and cognitive functions and cognitive reserve. Clin Exp Hypertens. 2016;38(1):95–99. doi: 10.3109/10641963.2015.1047946.Kilander L., Nyman H., Boberg M., Lithell H. The association between low diastolic blood pressure in middle age and cognitive function in old age. A population-based study. Age Ageing. 2000;29(3):243–248. doi: 10.1093/ageing/29.3.243.Kilander L., Nyman H., Boberg M., Lithell H. The association between low diastolic blood pressure in middle age and cognitive function in old age. A population-based study. Age Ageing. 2000;29(3):243–248. doi: 10.1093/ageing/29.3.243.Di Carlo A., Baldereschi M., Amaducci L., Maggi S., Grigoletto F., Scarlato G., Inzitari D. Cognitive impairment without dementia in older people: prevalence, vascular risk factors, impact on disability. The Italian Longitudinal Study on Aging. J Am Geriatr Soc. 2000;48(7):775–782. doi: 10.1111/j.1532-5415.2000.tb04752.x.Di Carlo A., Baldereschi M., Amaducci L., Maggi S., Grigoletto F., Scarlato G., Inzitari D. Cognitive impairment without dementia in older people: prevalence, vascular risk factors, impact on disability. The Italian Longitudinal Study on Aging. J Am Geriatr Soc. 2000;48(7):775–782. doi: 10.1111/j.1532-5415.2000.tb04752.x.Huang C.Q., Dong B.R., Zhang Y.L., Wu H.M., Liu Q.X., Flaherty J.H. Cognitive impairment and hypertension among Chinese nonagenarians and centenarians. Hypertens Res. 2009;32(7):554–558. doi: 10.1038/hr.2009.72.Huang C.Q., Dong B.R., Zhang Y.L., Wu H.M., Liu Q.X., Flaherty J.H. Cognitive impairment and hypertension among Chinese nonagenarians and centenarians. Hypertens Res. 2009;32(7):554–558. doi: 10.1038/hr.2009.72.Chen K.H., Henderson V.W., Stolwyk R.J., Dennerstein L., Szoeke C. Prehypertension in midlife is associated with worse cognition a decade later in middle-aged and older women. Age Ageing. 2015;44(3):439–445. doi: 10.1093/ageing/afv026.Chen K.H., Henderson V.W., Stolwyk R.J., Dennerstein L., Szoeke C. Prehypertension in midlife is associated with worse cognition a decade later in middle-aged and older women. Age Ageing. 2015;44(3):439–445. doi: 10.1093/ageing/afv026.Hannesdottir K., Nitkunan A., Charlton R.A., Barrick T.R., MacGregor G.A., Markus H.S. Cognitive impairment and white matter damage in hypertension: a pilot study. Acta Neurol Scand. 2009;119(4):261–268. doi: 10.1111/j.1600-0404.2008.01098.x.Hannesdottir K., Nitkunan A., Charlton R.A., Barrick T.R., MacGregor G.A., Markus H.S. Cognitive impairment and white matter damage in hypertension: a pilot study. Acta Neurol Scand. 2009;119(4):261–268. doi: 10.1111/j.1600-0404.2008.01098.x.Zakharov V.V., Vakhnina N.V., Parfenov V.A. Cognitive disorders and their treatment in hypertension. Meditsinskiy sovet = Medical Council. 2017;(1S):6–12. (In Russ.) doi: 10.21518/2079-701X-2017-0-6-12.Захаров В.В., Вахнина Н.В., Парфенов В.А. Когнитивные нарушения и их лечение при артериальной гипертензии. Медицинский совет. 2017;(1S):6–12. doi: 10.21518/2079-701X-2017-0-6-12.André-Petersson L., Elmståhl S., Hagberg B., Janzon L., Reinprecht F., Steen G. Is blood pressure at 68 an independent predictor of cognitive decline at 81? Results from follow-up study “Men born in 1914”, Malmö, Sweden. Aging Ment Health. 2003;7(1):61–72. doi: 10.1080/1360786021000007036.André-Petersson L., Elmståhl S., Hagberg B., Janzon L., Reinprecht F., Steen G. Is blood pressure at 68 an independent predictor of cognitive decline at 81? Results from follow-up study “Men born in 1914”, Malmö, Sweden. Aging Ment Health. 2003;7(1):61–72. doi: 10.1080/1360786021000007036.Ferreira J.P., Kearney Schwartz A., Watfa G., Zohra L., Felblinger J., Boivin J.M. et al. Memory Alterations and White Matter Hyperintensities in Elderly Patients With Hypertension: The ADELAHYDE-2 Study. J Am Med Dir Assoc. 2017;18(5):451.e13–451.e25. doi: 10.1016/j.jamda.2017.01.008.Ferreira J.P., Kearney Schwartz A., Watfa G., Zohra L., Felblinger J., Boivin J.M. et al. Memory Alterations and White Matter Hyperintensities in Elderly Patients With Hypertension: The ADELAHYDE-2 Study. J Am Med Dir Assoc. 2017;18(5):451.e13–451.e25. doi: 10.1016/j.jamda.2017.01.008.Yeung S.E., Loken Thornton W. “Do it-yourself”: Home blood pressure as a predictor of traditional and everyday cognition in older adults. PLoS One. 2017;12(5):e0177424. doi: 10.1371/journal.pone.0177424.Yeung S.E., Loken Thornton W. “Do it-yourself”: Home blood pressure as a predictor of traditional and everyday cognition in older adults. PLoS One. 2017;12(5):e0177424. doi: 10.1371/journal.pone.0177424.Peters R., Yasar S., Anderson C.S., Andrews S., Antikainen R., Arima H. et al. Investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis. Neurology. 2020;94(3):e267–e281. doi: 10.1212/WNL.0000000000008732.Peters R., Yasar S., Anderson C.S., Andrews S., Antikainen R., Arima H. et al. Investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis. Neurology. 2020;94(3):e267–e281. doi: 10.1212/WNL.0000000000008732.Levi Marpillat N., Macquin-Mavier I., Tropeano A.I., Bachoud-Levi A.C., Maison P. Antihypertensive classes, cognitive decline and incidence of dementia: a network meta-analysis. J Hypertens. 2013;31(6):1073–1082. doi: 10.1097/HJH.0b013e3283603f53.Levi Marpillat N., Macquin-Mavier I., Tropeano A.I., Bachoud-Levi A.C., Maison P. Antihypertensive classes, cognitive decline and incidence of dementia: a network meta-analysis. J Hypertens. 2013;31(6):1073–1082. doi: 10.1097/HJH.0b013e3283603f53.Ding J., Davis-Plourde K.L., Sedaghat S., Tully P.J., Wang W., Phillips C. et al. Antihypertensive medications and risk for incident dementia and Alzheimer’s disease: a meta-analysis of individual participant data from prospective cohort studies. Lancet Neurol. 2020;19(1):61–70. doi: 10.1016/S1474-4422(19)30393-X.Ding J., Davis-Plourde K.L., Sedaghat S., Tully P.J., Wang W., Phillips C. et al. Antihypertensive medications and risk for incident dementia and Alzheimer’s disease: a meta-analysis of individual participant data from prospective cohort studies. Lancet Neurol. 2020;19(1):61–70. doi: 10.1016/S1474-4422(19)30393-X.Parfenov V.A., Starchina Y.A. Cognitive disorders in patients with essential hypertension and their treatment. Neurology, Neuropsychiatry, Psychosomatics. 2011;3(1):27–33. (In Russ.) doi: 10.14412/2074-2711-2011-130.Парфенов В.А., Старчина Ю.А. Когнитивные нарушения у пациентов с артериальной гипертензией и их лечение. Неврология, нейропсихиатрия, психосоматика. 2011;3(1):27–33. doi: 10.14412/2074-2711-2011-130.Saletu B., Garg A., Shoeb A. Safety of nicergoline as an agent for management of cognitive function disorders. Biomed Res Int. 2014;2014:610103. doi: 10.1155/2014/610103.Saletu B., Garg A., Shoeb A. Safety of nicergoline as an agent for management of cognitive function disorders. Biomed Res Int. 2014;2014:610103. doi: 10.1155/2014/610103.Azimova Yu.E. Subjective cognitive impairement: modern view of the problem. Poliklinika. 2017;(2):62–64. (In Russ.) Available at: http://www.poliklin.ru/imagearticle/201702(2)/62.pdf.Азимова Ю.Э. Субъективные когнитивные нарушения: современный взгляд на проблему. Поликлиника. 2017;(2):62–64. Режим доступа: http://www.poliklin.ru/imagearticle/201702(2)/62.pdf.Bès A., Orgogozo J.M., Poncet M., Rancurel G., Weber M., Bertholom N. et al. A 24-month, double-blind, placebo-controlled multicentre pilot study of the efficacy and safety of nicergoline 60 mg per day in elderly hypertensive patients with leukoaraiosis. Eur J Neurol. 1999;6(3):313–322. doi: 10.1046/j.1468-1331.1999.630313.x.Bès A., Orgogozo J.M., Poncet M., Rancurel G., Weber M., Bertholom N. et al. A 24-month, double-blind, placebo-controlled multicentre pilot study of the efficacy and safety of nicergoline 60 mg per day in elderly hypertensive patients with leukoaraiosis. Eur J Neurol. 1999;6(3):313–322. doi: 10.1046/j.1468-1331.1999.630313.x.Nappi G., Bono G., Merlo P., Borromei A., Caltagirone C., Lomeo C. et al. Long-term nicergoline treatment of mild to moderate senile dementia: results of a multicentre, double-blind, placebo-controlled study. Clin Drug Investig. 1997;13(6):308–316. doi: 10.2165/00044011-199713060-00003.Nappi G., Bono G., Merlo P., Borromei A., Caltagirone C., Lomeo C. et al. Long-term nicergoline treatment of mild to moderate senile dementia: results of a multicentre, double-blind, placebo-controlled study. Clin Drug Investig. 1997;13(6):308–316. doi: 10.2165/00044011-199713060-00003.Battaglia A., Bruni G., Ardia A., Sacchetti G., Baroni A., Cisbani R. et al. Nicergoline in mild to moderate dementia. A multicenter, double-blind, placebo-controlled study. J Am Geriatr Soc. 1989;37(4):295–302. doi: 10.1111/j.1532-5415.1989.tb05494.x.Battaglia A., Bruni G., Ardia A., Sacchetti G., Baroni A., Cisbani R. et al. Nicergoline in mild to moderate dementia. A multicenter, double-blind, placebo-controlled study. J Am Geriatr Soc. 1989;37(4):295–302. doi: 10.1111/j.1532-5415.1989.tb05494.x.Fioravanti M., Flicker L. Nicergoline for dementia and other age associated forms of cognitive impairment. Cochrane Database Syst Rev. 2001;2001(4):CD003159. doi: 10.1002/14651858.CD003159.Fioravanti M., Flicker L. Nicergoline for dementia and other age associated forms of cognitive impairment. Cochrane Database Syst Rev. 2001;2001(4):CD003159. doi: 10.1002/14651858.CD003159.Кuznetsova S. М. Effects of nicegoline on cerebral, systemic and cardiac hemodynamics in the geriatric patients who survived an ischemic stroke. Problemy stareniya i dolgoletiya = Problems of aging and longevity. 2011;20(3):326–334. (In Russ.) Available at: http://www.geront.kiev.ua/psid-2010/2011_3.pdf.Кузнецова С. М. Влияние ницерголина на церебральную, системную и кардиальную гемодинамику у больных пожилого возраста, перенесших ишемический инсульт. Проблемы старения и долголетия. 2011;20(3):326–334. Режим доступа: http://www.geront.kiev.ua/psid-2010/2011_3.pdf.Fioravanti M., Nakashima T., Xu J., Garg A. A systematic review and metaanalysis assessing adverse event profile and tolerability of nicergoline. BMJ Open. 2014;4(7):e005090. doi: 10.1136/bmjopen-2014-005090.Fioravanti M., Nakashima T., Xu J., Garg A. A systematic review and metaanalysis assessing adverse event profile and tolerability of nicergoline. BMJ Open. 2014;4(7):e005090. doi: 10.1136/bmjopen-2014-005090.Korsunskaya L.L., Miklyaev A.A. Nicergolin (Sermion) prophylactic efficacy assessment on the brain functioning in elderly patients. Krymskiy terapevticheskiy zhurnal = Crimean Journal of Internal Diseases. 2006;(1):86–94. (In Russ.) Available at: http://crimtj.ru/Journal.files/5-2006-1/86.pdf.Корсунская Л.Л., Микляев А.А. Анализ эффективности комплексного профилактического воздействия ницерголина (сермиона) на функциональные показатели деятельности головного мозга у лиц пожилого возраста. Крымский терапевтический журнал. 2006;(1):86–94. Режим доступа: http://crimtj.ru/Journal.files/5-2006-1/86.pdf.Violan C., Foguet-Boreu Q., Flores-Mateo G., Salisbury C., Blom J., Freitag M. et al. Prevalence, determinants and patterns of multimorbidity in primary care: a systematic review of observational studies. PLoS One. 2014;9(7):e102149. doi: 10.1371/journal.pone.0102149.Violan C., Foguet-Boreu Q., Flores-Mateo G., Salisbury C., Blom J., Freitag M. et al. Prevalence, determinants and patterns of multimorbidity in primary care: a systematic review of observational studies. PLoS One. 2014;9(7):e102149. doi: 10.1371/journal.pone.0102149.Sychev D.A., Otdelеnov V.A., Krasnova N.M., Ilyina E.S. Polypragmasy: A clinical pharmacologist’s view. Terapevticheskii Arkhiv = Terapevticheskii Arkhiv. 2016;(12):94–102. (In Russ.) doi: 10.17116/terarkh2016881294-102.Сычев Д.А., Отделенов В.А., Краснова Н.М., Ильина Е.С. Полипрагмазия: взгляд клинического фармаколога. Терапевтический архив. 2016;(12):94–102. doi: 10.17116/terarkh2016881294-102.Park H.Y., Park J.W., Song H.J., Sohn H.S., Kwon J.W. The Association between polypharmacy and dementia: a nested case-control study based on a 12-year longitudinal cohort database in South Korea. PLoS One. 2017;12(1):e0169463. doi: 10.1371/journal.pone.0169463.Park H.Y., Park J.W., Song H.J., Sohn H.S., Kwon J.W. The Association between polypharmacy and dementia: a nested case-control study based on a 12-year longitudinal cohort database in South Korea. PLoS One. 2017;12(1):e0169463. doi: 10.1371/journal.pone.0169463.Cherniaeva M.S., Ostroumova O.D., Sychev D.A. Drug-induced orthostatic hypotension. Klinicheskaya farmakologiya i terapiya = Clinical pharmacology and therapy. 2018;27(5):57–63. (In Russ.) doi: 10.32756/0869-5490-2018-5-57-63.Черняева М.С., Остроумова О.Д., Сычев Д.А. Лекарственно индуцированная ортостатическая гипотензия. Клиническая фармакология и терапия. 2018;27(5):57–63. doi: 10.32756/0869-5490-2018-5-57-63.Oganov R.G., Simanenkov V.I., Bakulin I.G., Bakulina N.V., Barbarash O.L., Boytsov S.A. et al. Comorbidities in clinical practice. Algorithms for diagnostics and treatment. Kardiovaskulyarnaya terapiya i profilaktika = Cardiovascular Therapy and Prevention. 2019;18(1):5–66. (In Russ.) doi: 10.15829/1728-8800-2019-1-5-66.Оганов Р.Г., Симаненков В.И., Бакулин И.Г., Бакулина Н.В., Барбараш О.Л., Бойцов С.А. и др. Коморбидная патология в клинической практике. Алгоритмы диагностики и лечения. Кардиоваскулярная терапия и профилактика. 2019;18(1):5–66. doi: 10.15829/1728-8800-2019-1-5-66.Оганов Р.Г., Симаненков В.И., Бакулин И.Г., Бакулина Н.В., Барбараш О.Л., Бойцов С.А. и др. Коморбидная патология в клинической практике. Алгоритмы диагностики и лечения. Кардиоваскулярная терапия и профилактика. 2019;18(1):5–66. doi: 10.15829/1728-8800-2019-1-5-66.

The authors declare that there are no conflicts of interest present.