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Possibilities of drug therapy for vascular cognitive impairment: a critical view and possible compromises

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To manage patients with vascular cognitive impairment (VCI) is an extremely difficult task, since drug therapy algorithms have not been elaborated, whereas the prescription of most drugs has not always been pathogenetically justified. Today, both our country and foreign countries have no uniform standards for VCI treatment, and the choice of drugs in everyday clinical practice is largely determined by a physician’s personal experience. The paper discusses main areas in the drug treatment of VCI and provides a detailed analysis of studies evaluating the efficacy and safety of basic drugs used to correct cognitive deficit. The basic anti-dementia medications (akatinol memantine and acetylcholinesterase inhibitors) recommended as mandatory treatment have been identified. The remaining groups of drugs are proposed to be used in combination therapy as add-on treatment, by taking into account individual indications. It is concluded that add-on investigations are needed to select the treatment algorithm differentiated preferably for different clinical and pathogenic VCI variants, which should also consider not only the features of clinical manifestations, but also the magnitude of structural and functional changes in the cerebral vessels and brain matter.

About the Authors

A. Yu. Emelin
S.M. Kirov Military Medical Academy, Ministry of Defense of Russia
Russian Federation

Andrey Yuryevich Emelin

Department of Nervous System Diseases

6, Academician Lebedev St., Saint Petersburg 194044

V. Yu. Lobzin
S.M. Kirov Military Medical Academy, Ministry of Defense of Russia; I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia
Russian Federation

Department of Nervous System Diseases

Acad. S.N. Davidenkov Department of Neurology

6, Academician Lebedev St., Saint Petersburg 194044
41, Kirochnaya St., Saint Petersburg 191015 


1. Erkinjuntti T, Roman G, Gauthier S, et al. Emerging therapies for vascular dementia and vascular cognitive impairment. Stroke. 2004;35:1010. doi: 10.1161/01.STR.0000120731.88236.33

2. Osteen C, Giza C, Hovda D. Injury-induced alterations in N-methyl-d-aspartate receptor subunit composition contribute to prolonged (45)calcium accumulation following lateral fluid percussion. Neuroscience. 2004;128(2):305-22.

3. Areosa SA, Sherriff F, McShane R. Memantine for dementia. Cochrane Database Syst Rev. 2005;(3):CD003154. doi: 10.1002/14651858.CD003154.pub3

4. Orgogozo J-M, Rigaud A-S, Stöffler A, et al. Efficacy and safety of memantine in patients with mild to moderate vascular dementia: a randomized, placebo-controlled trial (MMM 300). Stroke. 2002;33:1834-9.

5. 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;17:297-305.

6. Folch J. Memantine for the treatment of dementia: a review on its current and future applications. Alzheimers Dis. 2018;62(3):1223-40. doi: 10.3233/JAD-170672

7. Yakhno NN, Preobrazhenskaya IS, Zakharov VV, Mkhitaryan EA. Efficiency akatinol memantin at patients with nedementny cognitive frustration. Results of multicenter clinical supervision. Nevrologicheskii zhurnal. 2010;(2):52-8 (In Russ.).

8. Matsunaga S, Kishi T, Iwata N. Memantine monotherapy for Alzheimer's disease: a systematic review and meta-analysis. PLoS One. 2015 Apr 10;10(4):e0123289. doi: 10.1371/journal.pone.0123289

9. Chen YD, Zhang J, Wang Y, et al. Efficacy of cholinesterase inhibitors in vascular dementia: an updated meta-analysis. Eur Neurol. 2016;75(3-4):132-41. doi: 10.1159/000444253

10. Black S, Roman GC, Geldmacher DS, et al; Donepezil 307 Vascular Dementia Study Group. Efficacy and tolerability of donepezil in vascular dementia: positive results of a 24-week, multicenter, international, randomized, placebo-controlled clinical trial. Stroke. 2003 Oct;34:2323-30. doi: 10.1161/01.STR.0000091396.95360.E1

11. Wilkinson D, Doody R, Helme R, et al; Donepezil 308 Study Group. Donepezil in vascular dementia: a randomized, placebo-controlled study. Neurology. 2003;61:479-86. doi: 10.1212/01.WNL.0000078943.50032.FC

12. Erkinjuntti T, Kurz A, Gauthier S, et al. Efficacy of galantamine in probable vascular dementia and Alzheimer's disease combined with cerebrovascular disease: a randomised trial. Lancet. 2002;359:1283-90. doi: 10.1016/S01406736(02)08267-3

13. Ballard C, Sauter M, Scheltens P, et al. Efficacy, safety and tolerability of rivastigmine capsules in patients with probable vascular dementia: the VantagE study. Curr Med Res Opin. 2008;24(9)2561-74. doi: 10.1185/03007990802328142

14. Moretti R, Torre P, Antonello RM, et al. Rivastigmine in subcortical vascular dementia: an open 22-month study. J Neurol Sci. 2002;203204:141-6. doi: 10.1016/S0022-510X(02)00280-0

15. Moretti R, Torre P, Antonello RM, et al. Rivastigmine in subcortical vascular dementia: a randomized, controlled, open 12-month study in 208 patients. Am J Alzheimers Dis Other Demen. 2003;18:265-72. doi: 10.1177/153331750301800508

16. Order of the Ministry of Health of the Russian Federation of 20.12.2012 No. 1228n «On approval of the standard of specialized medical care for Alzheimer's disease» (In Russ.).

17. Fioravanti M, Yanagi M. Cytidinediphosphocholine (CDP choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly. Cochrane Database Syst Rev. 2005 Apr 18;(2):CD000269. doi: 10.1002/14651858

18. Cotroneo AM, Castagna A, Putignano S, et al. Effectiveness and safety of citicoline in mild vascular cognitive impairment: the IDEALE study. Clin Interv Aging. 2013;8:131-7. doi: 10.2147/CIA.S38420

19. Alvarez-Sabin J, Ortega G, Jacas C, et al. Long-term treatment with citicoline may improve poststroke vascular cognitive impairment. Cerebrovasc Dis. 2013;35(2):146-54. doi: 10.1159/000346602

20. Zakharov VV. National program for research on the epidemiology and therapy of cognitive disorders in the elderly («Prometheus»). Nevrologicheskii zhurnal. 2006;11(2):27-32 (In Russ.).

21. Parfenov VA, Ostroumova OD, Ostroumova TM, et al. Vascular cognitive impairment: pathophysiological mechanisms, insights into structural basis, and perspectives in specific treatments. Neuropsychiatr Dis Treat. 2019 May 21;15:1381-402. doi: 10.2147/NDT.S197032

22. Fioravanti M, Flicker L. Efficacy of nicergoline in dementia and other age associated forms of cognitive impairment. Cochrane Database Syst Rev. 2001;(4):CD003159. doi: 10.1002/14651858.CD003159

23. Winblad B, Fioravanti M, Dolezal T, et al. Therapeutic use of nicergoline. Clin Drug Investig. 2008;28(9):533-52. doi: 10.2165/00044011-200828090-00001

24. Szatmari SZ, Whitehouse PJ. Vinpocetine for cognitive impairment and dementia. Cochrane Database Syst Rev. 2003;(1):CD003119. doi: 10.1002/14651858.CD003119

25. Sha MC, Callahan CM. The efficacy of pentoxifylline in the treatment of vascular dementia: a systematic review. Alzheimer Dis Assoc Disord. 2003;17(1):46-54. doi: 10.1097/00002093-200301000-00006

26. Tomassoni D, Lanari A, Silvestrelli G, et al. Nimodipine and its use in cerebrovascular disease: evidence from recent preclinical and controlled clinical studies. Clin Exp Hypertens. 2008 Nov;30(8):744-66. doi: 10.1080/10641960802580232

27. Pantoni L, der Ser T, Soglian A. Efficacy and safety of nimodipine in subcortical vascular dementia. Stroke. 2005;36:619-24. doi: 10.1161/01.STR.0000155686.73908.3e

28. Yakhno NN, Zakharov VV, Lokshina FB, et al. Tanakan (EGb 761) in the treatment of mild cognitive impairment (multicenter study). Zhurnal nevrologii ipsikhiatrii im. S.S. Korsakova. 2006;106(12):48-53 (In Russ.).

29. Weinmann S, Roll S, Schwarzbach C, et al. Effects of Ginkgo biloba in dementia: systematic review and meta-analysis. BMC Geriatr. 2010;(10):14. doi: 10.1186/1471-2318-10-14

30. Smith E, Cieslak A, Barber P, et al. Therapeutic strategies and drug development for vascular cognitive impairment. J Am Heart Assoc. 2017;6(5):1-12. doi: 10.1161/JAHA.117.005568

31. Flicker L, Grimley Evans G. Piracetam for dementia or cognitive impairment. Cochrane Database Syst Rev. 2001;(2):CD001011. doi: 10.1002/14651858

32. Guekht AB, Moessler H, Novak PH, Gusev EI. Cerebrolysin Investigators. Cerebrolysin in vascular dementia: improvement of clinical outcome in a randomized, double-blind, placebo-controlled multicenter trial. J Stroke Cerebrovasc Dis. 2011 Jul-Aug;20(4):310-8. doi: 10.1016/j.jstrokecerebrovasdis.2010.01.012

33. Shuhui Cui, Ning Chen, Mi Yang, et al. Cerebrolysin for vascular dementia. Cochrane Database Syst Rev. 2019 Nov 11;2019(11):CD008900. doi: 10.1002/14651858.CD008900.pub3

34. Guekht A, Skoog I, Edmundson S, et al; ARTEMIDA Trial (A Randomized Trial of Efficacy, 12 Months International Double-Blind Actovegin): a randomized controlled trial to assess the efficacy of actovegin in poststroke cognitive impairment. Stroke. 2017 May;48(5):1262-70. doi: 10.1161/STROKEAHA.116.014321

35. Kavirajan H, Schneider LS. Efficacy and adverse effects of cholinesterase inhibitors and memantine in vascular dementia: a meta-analysis of randomised controlled trials. Lancet Neurol. 2007 Sep;6(9):782-92. doi: 10.1016/S1474-4422(07)70195-3

36. Schmidt R, Hofer E, Bouwman FH, et al. EFNS-ENS/EAN Guideline on concomitant use of cholinesterase inhibitors and memantine in moderate to severe Alzheimer's disease. Eur J Neurol. 2015 Jun;22(6):889-98. doi: 10.1111/ene.12707

37. Kabir T, Uddin S, Al Mamun A, et al. Combination drug therapy for the management of Alzheimer's disease. Int J Mol Sci. 2020 May 5;21(9):3272. doi: 10.3390/ijms21093272

38. Castagna A, Cotroneo AM, Ruotolo G, Gareri P. The CITIRIVAD Study: CITIcoline plus RIVAstigmine in Elderly Patients Affected with Dementia Study. Clin Drug Investig. 2016;36:1059-65. doi: 10.1007/s40261-016-0454-3

39. Gareri P, Castagna A, Cotroneo AM, et al. The Citicholinage Study: Citicoline Plus Cholinesterase Inhibitors in Aged Patients Affected with Alzheimer’s Disease Study. J Alzheimer’s Dis. 2017;56:557-65. doi: 10.3233/JAD-160808

40. Emelin AYu, Litvinenko IV, Lobzin VYu. Errors in the management of patients with Alzheimer's disease: analysis of problems and ways of their solution. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2019;11(4):141-6. doi: 10.14412/2074-2711-20194-141-146 (In Russ.).


For citations:

Emelin A.Yu., Lobzin V.Yu. Possibilities of drug therapy for vascular cognitive impairment: a critical view and possible compromises. Neurology, Neuropsychiatry, Psychosomatics. 2020;12(4):131-136. (In Russ.)

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