Neurology, Neuropsychiatry, Psychosomatics

Advanced search

Treatment of cognitive impairment in arterial hypertension

Full Text:


Cognitive impairment (CI) is one of the earliest and most frequent neurological disorders in patients with arterial hypertension. Arterial hypertension is a leading modifiable risk factor for stroke and cerebral microangiopathy, which underlies the development of non-stroke associated CI. Antihypertensive therapy plays an essential role in preventing the development and slowing the progression of CI by controlling blood pressure. The review discusses the use of memantine – a reversible inhibitor of NMDA receptors (akatinol memantine) – in vascular CI.

About the Authors

Yu. A. Starchina
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia
Russian Federation

Yulia Aleksandrovna Starchina

Department of Nervous System Diseases and Neurosurgery, N.V. Sklifosovsky Institute of Clinical Medicine

11, Rossolimo St., Build. 1, Moscow 119021

K. S. Sleptcova
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia
Russian Federation

Department of Nervous System Diseases and Neurosurgery, N.V. Sklifosovsky Institute of Clinical Medicine

11, Rossolimo St., Build. 1, Moscow 119021


1. Mills KT, Bundy JD, Kelly TN, et al. Global disparities of hypertension prevalence and control: a systematic analysis of population-based studies from 90 countries. Circulation. 2016 Aug 9;134(6):441-50. doi: 10.1161/CIRCULATIONAHA.115.018912

2. Muller DC, Murphy N, Johansson M, et al. Modifiable causes of premature death in middle-age in Western Europe: results from the EPIC cohort study. BMC Med. 2016 Jun 14;14:87. doi: 10.1186/s12916-016-0630-6

3. Kintscher U. The burden of hypertension. EuroIntervention. 2013 May;9 Suppl R:R12-5. doi: 10.4244/EIJV9SRA3

4. Akinyemi RO, Mukaetova-Ladinska EB, Attems J, et al. Vascular risk factors and neurodegeneration in ageing related dementias: Alzheimer's disease and vascular dementia. Curr Alzheimer Res. 2013 Jul;10(6):642-53. doi: 10.2174/15672050113109990037

5. Arvanitakis Z, Shah RC, Bennett DA. Diagnosis and management of dementia: review. JAMA. 2019 Oct 22;322(16):1589-99. doi: 10.1001/jama.2019.4782

6. De Leeuw FE, van Gijn J. Vascular dementia. Pract Neurol. 2003;3:86-91.

7. Cacciatore F, Abete P, Ferrara N, et al. The role of blood pressure in cognitive impairment in an elderly population. J Hypertens. 1997;15:135-42.

8. Elias MF, Wolf PA, D'Agostino RB, et al. Untreated blood pressure level is inversely related to cognitive functioning: the Framingham Study. Am J Epidemiol. 1993 Sep 15;138(6):353-64. doi: 10.1093/oxfordjournals.aje.a116868

9. Elliott WJ. Association of higher diastolic blood pressure levels with cognitive impairment. Yearbook Cardiol. 2010;2010:29-30.

10. Launer LJ, Masaki K, Petrovitch H, et al. The association between midlife blood pressure levels and late-life cognitive function. JAMA. 1995 Dec 20;274(23):1846-51.

11. Starr JM, Whalley LJ, Inch S, Shering PA. Blood pressure and cognitive functions in healthy old people. J Am Geriatr Soc. 1993 Jul;41(7):753-6. doi: 10.1111/j.1532-5415.1993.tb07466.x

12. Kilander L, Nyman H, Boberg M, et al. Hypertension is related to cognitive impairment; a 20-year follow-up of 999 men. Hypertension. 1998 Mar;31(3):780-6. doi: 10.1161/01.hyp.31.3.780

13. Carmelli D, Swan GE, Reed T, et al. Midlife cardiovascular risk factors, ApoE, and cognitive decline in elderly male twins. Neurology. 1998 Jun;50(6):1580-5. doi: 10.1212/wnl.50.6.1580

14. Singh-Manoux A, Marmot M. High blood pressure was associated with cognitive function in middle-age in the Whitehall II study. J Clin Epidemiol. 2005 Dec;58(12):1308-15. doi: 10.1016/j.jclinepi.2005.03.016

15. Teles de Menezes S, Giatti L, Campos Brant L, et al. Hypertension, Prehypertension, and Hypertension Control. Association With Decline in Cognitive Performance in the ELSABrasil Cohort. Hypertension. 2021 Feb;77(2):672-81. doi: 10.1161/HYPERTENSIONAHA.120.16080. Epub 2020 Dec 14.

16. Sabayan B, Wijsman L, Foster-Dingley JC, et al. Association of visit-to-visit variability in blood pressure with cogitive function in old age: A prospective cohort study. Brit Med J. 2013 Jul 29;347:f4600. doi: 10.1136/bmj.f4600

17. Rawlings AM, Juraschek SP, Heiss G, et al. Association of orthostatic hypotension with incident dementia, stroke, and cognitive decline. Neurology. 2018 Aug 21;91(8):e759-e768. doi: 10.1212/WNL.0000000000006027. Epub 2018 Jul 25.

18. Kivipelto M, Helkala EL, Hanninen T, et al. Midlife vascular risk factors and late-life mild cognitive impairment: A population-based study. Neurology. 2001 Jun 26;56(12):1683-9. doi: 10.1212/wnl.56.12.1683

19. Reitz C, Tang MX, Manly J, et al. Hypertension and the risk of mild cognitive impairment. Arch Neurol. 2007 Dec;64(12):1734-40. doi: 10.1001/archneur.64.12.1734

20. Gottesman RF, Schneider AL, Albert M, et al. Midlife hypertension and 20-year cognitive change: The atherosclerosis risk in communities neurocognitive study. JAMA Neurol. 2014 Oct;71(10):1218-27. doi: 10.1001/jamaneurol.2014.1646

21. Freitag MH, Peila R, Masaki K, et al. Midlife pulse pressure and incidence of dementia: The Honolulu-Asia Aging Study. Stroke. 2006 Jan;37(1):33-7. doi: 10.1161/01.STR.0000196941.58869.2d. Epub 2005 Dec 8.

22. Goldstein FC, Levey AI, Steenland NK. High blood pressure and cognitive decline in mild cognitive impairment. J Am Geriatr Soc. 2013 Jan;61(1):67-73. doi: 10.1111/jgs.12067. Epub 2013 Jan 10.

23. Wei J, Yin X, Liu Q, Tan L. Association between hypertension and cognitive function: A cross-sectional study in people over 45 years old in China. J Clin Hypertens (Greenwich). 2018 Nov;20(11):1575-83. doi: 10.1111/jch.13393. Epub 2018 Sep 26.

24. Gottesman RF, Albert MS, Alonso A, et al. Associations between midlife vascular risk factors and 25-year incident dementia in the atherosclerosis risk in communities (aric) cohort. JAMA Neurol. 2017 Oct 1;74(10):1246-54. doi: 10.1001/jamaneurol.2017.1658

25. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018 Jun;71(6):1269-324. doi: 10.1161/HYP.0000000000000066. Epub 2017 Nov 13.

26. Weidung B, Littbrand H, Nordström P, et al. The association between SBP and mortality risk differs with level of cognitive function in very old individuals. J Hypertens. 2016 Apr;34(4):745-52. doi: 10.1097/HJH.0000000000000831

27. The SPRINT MIND Investigators for the SPRINT Research Group. Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial. JAMA. 2019 Feb 12;321(6):553-61. doi: 10.1001/jama.2018.21442

28. Starchina YuA, Parfenov VA, Chazova IE, et al. Cognitive disorders in patients with hypertension. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2008;(4):39-43 (In Russ.).

29. Tatemichi TK, Desmond DW, Mayeux R, et al. Dementia after stroke: baseline frequency, risks, and clinical features in a hospitalized cohort. Neurology. 1992 Jun;42(6):1185-93. doi: 10.1212/wnl.42.6.1185

30. Pendlebury ST, Rothwell PM. Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and metaanalysis. Lancet Neurol. 2009 Nov;8(11):1006-18. doi: 10.1016/S1474-4422(09)70236-4. Epub 2009 Sep 24.

31. Prencipe M, Ferretti C, Casini AR, et al. Stroke, disability, and dementia: results of a population survey. Stroke. 1997 Mar;28(3):531-6. doi: 10.1161/01.str.28.3.531

32. Linden T, Skoog I, Fagerberg B, et al. Cognitive impairment and dementia 20 months after stroke. Neuroepidemiology. Jan-Apr 2004;23(1-2):45-52. doi: 10.1159/000073974

33. Douiri A, Rudd AG, Wolfe CD. Prevalence of post-stroke cognitive impairment: South London Stroke Register 1995–2010. Stroke. 2013 Jan;44(1):138-45. doi: 10.1161/STROKEAHA.112.670844. Epub 2012 Nov 13.

34. Snowdon DA, Greiner LH, Mortimer JA, et al. Brain infarction and the clinical expression of Alzheimer disease: the Nun Study. JAMA. 1997 Mar 12;277(10):813-7.

35. Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010 Jul;9(7):689-701. doi: 10.1016/S1474-4422(10)70104-6

36. Potter GM, Chappell FM, Morris Z, Wardlaw JM. Cerebral perivascular spaces visible onmagnetic resonance imaging: development of a qualitative rating scale and its observer reliability. Cerebrovasc Dis. 2015;39(3-4):224-31. doi: 10.1159/000375153. Epub 2015 Mar 19.

37. Koennecke HC. Cerebral microbleeds on MRI: prevalence, associations, and potential clinical implications. Neurology. 2006 Jan 24;66(2):165-71. doi: 10.1212/01.wnl.0000194266.55694.1e

38. Fisher CM. The arterial lesions underlying lacunes. Acta Neuropathol. 1968 Dec 18;12(1):1-15. doi: 10.1007/BF00685305

39. Van Uden IW, Tuladhar AM, de Laat KF, et al. White matter integrity anddepressive symptoms in cerebral small vesseldisease: the RUN DMC study. Am J Geriatr Psychiatry. 2015 May;23(5):525-35. doi: 10.1016/j.jagp.2014.07.002. Epub 2014 Jul 19.

40. Iadecola C. Hypertension and dementia. Hypertension. 2014 Jul;64(1):3-5. doi: 10.1161/HYPERTENSIONAHA.114.03040. Epub 2014 Apr 28.

41. Imaoka K, Kobayashi S, Fujihara S, et al. Leukoencephalopathy with cerebral amyloid angiopathy: a semiquantitative and morphometric study. J Neurol. 1999 Aug;246(8):661-6. doi: 10.1007/s004150050428

42. Meier IB, Gu Y, Guzaman VA, et al. Lobar microbleeds are associated with a decline in executive functioning in older adults. Cerebrovasc Dis. 2014;38(5):377-83. doi: 10.1159/000368998. Epub 2014 Nov 25.

43. White L, Small BJ, Petrovitch H, et al. Recent clinicalpathologic research on the causes of dementia in late life: update from the Honolulu-Asia aging study. J Geriatr Psychiatry Neurol. 2005 Dec;18(4):224-7. doi: 10.1177/0891988705281872

44. Troncoso JC, Zonderman AB, Resnick SM, et al. Effect of infarcts on dementia in the Baltimore longitudinal study of aging. Ann Neurol. 2008 Aug;64(2):168-76. doi: 10.1002/ana.21413

45. Greenberg SM, Vernooij MW, Cordonnier C, et al. Microbleed Study Group: Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol. 2009 Feb;8(2):165-74. doi: 10.1016/S1474-4422(09)70013-4

46. Rouhl RP, Damoiseaux JG, Lodder J, et al. Vascular inflammation in cerebral small vessel disease. Neurobiol Aging. 2012 Aug;33(8):1800-6. doi: 10.1016/j.neurobiolaging.2011.04.008. Epub 2011 May 23.

47. Kaiser D, Weise G, Möller K, et al. Spontaneous white matter damage, cognitive decline and neuroinflammation in middle-aged hypertensive rats: an animal model of early-stage cerebral small vessel disease. Acta Neuropathol Commun. 2014 Dec 18;2:169. doi: 10.1186/s40478-014-0169-8

48. Verhaaren BF, Vernooij MW, de Boer R, et al. High blood pressure and cerebral white matter lesion progression in the general population. Hypertension. 2013 Jun;61(6):1354-9. doi: 10.1161/HYPERTENSIONAHA.111.00430. Epub 2013 Mar 25.

49. Wiseman SJ, Doubal FN, Chappell FM, et al. Plasma biomarkers of inflammation, endothelial function and hemostasis in cerebral small vessel disease. Cerebrovasc Dis. 2015;40(3-4):157-64. doi: 10.1159/000438494. Epub 2015 Aug 8.

50. Schmidt H, Zeginigg M, Wiltgen M, et al. CHARGE Consortium Neurology Working Group: Genetic variants of the NOTCH3 gene in the elderly and magnetic resonance imaging correlates of age-related cerebral small vessel disease. Brain. 2011 Nov;134(Pt 11):3384-97. doi: 10.1093/brain/awr252. Epub 2011 Oct 17.

51. Rodrigue KM, Rieck JR, Kennedy KM, et al. Risk factors for β-amyloid deposition in healthy aging: vascular and genetic effects. JAMA Neurol. 2013 May;70(5):600-6. doi: 10.1001/jamaneurol.2013.1342

52. Farmer ME, Kittner SJ, Abbott RD, et al. Longitudinally measured blood pressure, antihypertensive medication use, and cognitive performance: the Framingham Study. J Clin Epidemiol. 1990;43(5):475-80. doi: 10.1016/0895-4356(90)90136-d

53. Forette F, Seux ML, Staessen JA, et al. The prevention of dementia with antihypertensive treatment. New evidence from the Systolic Hypertension in Europe (Syst-Eur) study. Arch Intern Med. 2002 Oct 14;162(18):2046-52. doi: 10.1001/archinte.162.18.2046

54. Chang-Quan H, Hui W, Chao-Min W. The association of antihypertensive medication use with risk of cognitive decline and dementia: a meta-analysis of longitudinal studies. Int J Clin Pract. 2011 Dec;65(12):1295-305. doi: 10.1111/j.1742-1241.2011.02810.x

55. Tzourio C, Dufouil C, Ducimetiere P, et al. Cognitive decline in individuals with highblood pressure: a longitudinal study in the elderly. EVA Group. Neurology. 1999 Dec 10;53(9):1948-52. doi: 10.1212/wnl.53.9.1948

56. Tzourio C, Anderson C, Chapman N, et al. PROGRESS Collaborative Group. Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med. 2003 May 12;163(9):1069-75. doi: 10.1001/archinte.163.9.1069

57. Coca A, Monteagudo E, Domenech M, et al. Can the treatment of hypertension in the middleaged prevent dementia in the elderly? High Blood Press Cardiovasc Prev. 2016 Jun;23(2):97-104. doi: 10.1007/s40292-016-0144-5. Epub 2016 Apr 13.

58. Levi Marpillat N, Macquin-Mavier I, Tropeano AI, et al. Antihypertensive classes, cognitive decline and incidence of dementia: a network meta-analysis. J Hypertens. 2013 Jun;31(6):1073-82. doi: 10.1097/HJH.0b013e3283603f53

59. Iadecola C, Gottesman RF. Neurovascular and Cognitive Dysfunction in Hypertension. Circ Res. 2019 Mar 29;124(7):1025-1044. doi: 10.1161/CIRCRESAHA.118.313260

60. Parfenov VA, Starchina YuA, Yakhno NN. Eprosartan (Teveten) in the prevention of recurrent stroke and cognitive impairment. Nevrologicheskiy zhurnal. 2007;(1):46-51 (In Russ.).

61. Yakhno NN, Zakharov VV, Lokshina AB, et al. Dementsii: rukovodstvo dlya vrachey [Dementia: a guide for doctors]. Moscow: MEDpress-inform; 2010. 272 p. (In Russ.).

62. Gavrilova SI. Farmakoterapiya bolezni Al'tsgeymera [Pharmacotherapy for Alzheimer's disease]. Moscow: Pulse; 2003. 319 p. (In Russ.).

63. Bonfoco E, Krainc D, Ankarcrona M, et al. Apoptosis and necrosis: two distinct events induced, respectively, by mild and intense insults with N-methyl-D-aspartate or nitric oxide/superoxide in cortical cell cultures. Proc Natl Acad Sci USA. 1995 Aug 1;92(16):7162-6. doi: 10.1073/pnas.92.16.7162

64. Chan SL, Lu C, Mattson MP. Modification of cysteine proteases and AMPA receptor subunits by the lipid peroxidation product 4-hydroxynonenal: Impact on neuronal apoptosisand necrosis. Neurobiol Aging. 2000;21(1S):S17.

65. Mark LP, Prost RW, Ulmer JL, et al. Pictorial review of glutamate excitotoxicity: Fundamental concepts for neuroimaging. AJNR Am J Neuroradiol. Nov-Dec 2001;22(10):1813-24.

66. Kornhuber J, Wiltfang J. The role glutamatein dementia. J Neural Transm Suppl. 1998;53:277-87. doi: 10.1007/978-3-7091-6467-9-24

67. Farooq MU, Min J, Goshgarian C, Gorelick PB. Pharmacotherapy for Vascular Cognitive Impairment. CNS Drugs. 2017 Sep;31(9):759-76. doi: 10.1007/s40263-017-0459-3

68. Reisberg B, Doody R, Stöffler A, et al. Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med. 2003 Apr 3;348(14):1333-41. doi: 10.1056/NEJMoa013128

69. Van Dyck CH, Schmitt FA, Olin JT. A responder analysis of memantine treatment in patients with Alzheimer's disease maintained on donepezil. Am J Geriatr Psychiatry. 2006 May;14(5):428-37. doi: 10.1097/01.JGP.0000203151.17311.38

70. Frankiewicz T, Pilc A, Parsons CG. Differential effects of NMDA-receptor antagonists on long-term potentiation and hypoxic/hypoglycaemic excitotoxicity in hippocampal slices. Neuropharmacology. 2000 Feb 14;39(4):631-42. doi: 10.1016/s0028-3908(99)00168-9

71. McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD003154. doi: 10.1002/14651858.CD003154.pub5

72. Orgogozo JM, Rigaud AS, Stöffler A, et al. Efficacy and safety of memantine in patients with mild tomoderate vascular dementia: a randomized, placebo-controlled trial (MMM 300). Stroke. 2002 Jul;33(7):1834-9. doi: 10.1161/01.str.0000020094.08790.49

73. Wilcock G, Möbius HJ, Stöffler A; MMM 500 Group. A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM500). Int Clin Psychopharmacol. 2002 Nov;17(6):297-305. doi: 10.1097/00004850-200211000-00005

74. Yahno NN, Preobrazhenskaya IS, Zakharov VV, Mkhitaryan EA. The effectiveness of memantine administraton in patients with non-dementia cognitive impairment. The results of a multicentre clinical follow-up study. Rossiyskiy nevrologicheskiy zhurnal = Russian Neurological Journal. 2019;(3):37-44. doi: 10.30629/2658-7947-2019-24-3-37-44 (In Russ.).

75. Ballard C, Bannister C, Graham C, et al. Associations of psychotic symptoms in dementia sufferers. Brit J Psychiatry. 1995 Oct;167(4):537-40. doi: 10.1192/bjp.167.4.537

76. Bouman WP, Pinner G. Use of atypical antipsychotic drugs in old age psychiatry. Adv Psychiatr Treat. 2002;8:49-58.

77. Briesacher BA, Limcangco MR, Simoni-Wastila L, et al. The Quality of Antipsychotic Drug Prescribing in Nursing Homes. Arch Intern Med. 2005 Jun 13;165(11):1280-5. doi: 10.1001/archinte.165.11.1280

78. Buckley N, Sanders P. Cardiovascular adverse effects of antipsychotic drugs. Drug Saf. 2000 Sep;23(3):215-28. doi: 10.2165/00002018-200023030-00004

79. Burke AD, Tariot PN. Atypical antipsychotics in the elderly: a review of therapeutic trends and clinical outcomes. Expert Opin Pharmacother. 2009 Oct;10(15):2407-14. doi: 10.1517/14656560903200659

80. Schneider LS, Tariot PN, Dagerman KS, et al. CATIE-AD Study Group. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Engl J Med. 2006 Oct 12;355(15):1525-38. doi: 10.1056/NEJMoa061240

81. Gill SS, Bronskill SE, Normand SL, Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med. 2007 Jun 5;146(11):775-86. doi: 10.7326/0003-4819-146-11-200706050-00006

82. Gerhard T, Huybrechts K, Olfson M, Comparative mortality risks of antipsychotic medications in communitydwelling older adults. Br J Psychiatry. 2014 Jul;205(1):44-51. doi: 10.1192/bjp.bp.112.122499. Epub 2013 Aug 8.

83. Wilcock GK, Ballard CG, Cooper JA, et al. Memantine for agitation/aggression and psychosis in moderately severe to severe Alzheimer's disease: a pooled analysis of 3 studies. J Clin Psychiatry. 2008 Mar;69(3):341-8. doi: 10.4088/jcp.v69n0302

For citation:

Starchina Yu.A., Sleptcova K.S. Treatment of cognitive impairment in arterial hypertension. Neurology, Neuropsychiatry, Psychosomatics. 2021;13(5):90-95. (In Russ.)

Views: 75

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

ISSN 2074-2711 (Print)
ISSN 2310-1342 (Online)