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Atrial fibrillation and cognitive impairment: cerebral microbleeds as a new risk factor and possibilities of anticoagulant therapy (Part 2)

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Atrial fibrillation (AF) and cognitive impairment (CI) are among the most important problems of the modern health care system, which are characterized by an extremely high prevalence with the increasing trend of the latter; they lead to lower quality of life, shorter duration, and a larger number of disabled people. The specific feature of AF and CI is the presence of common risk factors. To date, the data of an increasing number of studies allow cerebral microbleeds (CMBs) to be considered as a new risk factor for CI, inter alia in patients with AF. In recent years, special attention has been paid to the role of oral anticoagulants (OACs) in the prevention of CI in AF, which is reflected in a number of studies and meta-analyses. In terms of the effect of OACs on the risk of CMBs, there is reason to believe that the latter increases with the use of warfarin, the effects of direct OACs (DOAC) in this regard require further investigation. At the same time, among the DOACs, apixaban is the only drug that has been proven to have no negative effect on the risk of CMBs in a randomized controlled clinical trial. In general, the available data indicate the positive effect of OACs in reducing the risk of CI and dementia in AF; moreover, DOACs have an advantage in this respect. Among the DOACs, apixaban is promising due to its optimal efficacy and safety profile.

About the Authors

O. D. Ostroumova
Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia; I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia
Russian Federation

Olga Dmitrievna Ostroumova

2/1, Barrikadnaya St., Build. 1, Moscow 125993
8, Trubetskaya St., Build. 2, Moscow 119991 

A. I. Kochetkov
Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia
Russian Federation
2/1, Barrikadnaya St., Build. 1, Moscow 125993

T. M. Ostroumova
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia
Russian Federation
8, Trubetskaya St., Build. 2, Moscow 119991


1. Wilson D, Jäger HR, Werring DJ. Anticoagulation for Atrial Fibrillation in Patients with Cerebral Microbleeds. Curr Atheroscler Rep. 2015 Aug;17(8):47. doi: 10.1007/s11883-015-0524-7

2. Fisher TJ, Schwartz AC, Greenspan HN, Heinrich TW. Dementia: A complex disease with multiple etiologies and multiple treatments. Int J Psychiatry Med. 2016;51(2):171-81. doi: 10.1177/0091217416636579. Epub 2016 Mar 3.

3. Parfenov VA. Combination and mutual influence of Alzheimer's disease and cerebrovascular pathology. Meditsinskii sovet. 2019;(9):8-13 (In Russ.).

4. Romero JR, Beiser A, Himali JJ, et al. Cerebral microbleeds and risk of incident dementia: the Framingham Heart Study. Neurobiol Aging. 2017 Jun;54:94-9. doi: 10.1016/j.neurobiolaging.2017.02.018. Epub 2017 Mar 6.

5. Zhang C, Gu ZC, Shen L, et al. Non-vitamin K antagonist oral anticoagulants and cognitive impairment in atrial fibrillation: insights from the meta-analysis of over 90,000 patients of randomized controlled trials and real-world studies. Front Aging Neurosci. 2018 Oct 2;10:258. doi: 10.3389/fnagi.2018.00258. eCollection 2018.

6. Zakharov VV, Vakhnina NV, Parfenov VA. Cognitive disorders and their treatment in hypertension. Meditsinskii sovet. 2017;(1S):6-12 (In Russ.).

7. Akoudad S, Wolters FJ, Viswanathan A, et al. Association of cerebral microbleeds with cognitive decline and dementia. JAMA Neurol. 2016 Aug 1;73(8):934-43. doi: 10.1001/jamaneurol.2016.1017

8. Kulesh AA, Drobakha VE, Shestakov VV. Cerebral small vessel disease: classification, clinical manifestations, diagnosis, and features of treatment. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2019;11(3S):4-17 (In Russ.). doi: 10.14412/2074-2711-2019-3S-4-17

9. Yates PA, Villemagne VL, Ellis KA, et al. Cerebral microbleeds: a review of clinical, genetic, and neuroimaging associations. Front Neurol. 2014 Jan 6;4:205. doi: 10.3389/fneur.2013.00205

10. Poels MM, Vernooij MW, Ikram MA, et al. Prevalence and risk factors of cerebral microbleeds: an update of the Rotterdam scan study. Stroke. 2010 Oct;41(10 Suppl):S103-6. doi: 10.1161/STROKEAHA.110.595181

11. Horstmann S, Möhlenbruch M, Wegele C, et al. Prevalence of atrial fibrillation and association of previous antithrombotic treatment in patients with cerebral microbleeds. Eur J Neurol. 2015 Oct;22(10):1355-62. doi: 10.1111/ene.12608. Epub 2014 Dec 30.

12. Song TJ, Kim J, Lee HS, et al. The frequency of cerebral microbleeds increases with CHADS(2) scores in stroke patients with nonvalvular atrial fibrillation. Eur J Neurol. 2013 Mar;20(3):502-8. doi: 10.1111/ene.12003. Epub 2012 Oct 11.

13. Chatzikonstantinou A, Willmann O, Szabo K, Hennerici MG. Cerebral microbleeds are uncommon in ischemic stroke associated with nonvalvular atrial fibrillation. J Neuroimaging. 2011 Apr;21(2):103-7. doi: 10.1111/j.1552-6569.2009.00440.x

14. Song TJ, Kim J, Song D, et al. Association of cerebral microbleeds with mortality in stroke patients having atrial fibrillation. Neurology. 2014 Oct 7;83(15):1308-15. doi: 10.1212/WNL.0000000000000862. Epub 2014 Sep 3.

15. Charidimou A, Karayiannis C, Song TJ, et al. Brain microbleeds, anticoagulation, and hemorrhage risk: Meta-analysis in stroke patients with AF. Neurology. 2017 Dec 5;89(23):2317-26. doi: 10.1212/WNL.0000000000004704. Epub 2017 Nov 8.

16. Yakushiji Y, Nishiyama M, Yakushiji S, et al. Brain microbleeds and global cognitive function in adults without neurological disorder. Stroke. 2008 Dec;39(12):3323-8. doi: 10.1161/STROKEAHA.108.516112. Epub 2008 Aug 7.

17. Charidimou A, Shams S, Romero JR, et al. Clinical significance of cerebral microbleeds on MRI: A comprehensive meta-analysis of risk of intracerebral hemorrhage, ischemic stroke, mortality, and dementia in cohort studies (v1). Int J Stroke. 2018 Jul;13(5):454-68. doi: 10.1177/1747493017751931. Epub 2018 Jan 17.

18. Miwa K, Tanaka M, Okazaki S, et al. Multiple or mixed cerebral microbleeds and dementia in patients with vascular risk factors. Neurology. 2014 Aug 12;83(7):646-53. doi: 10.1212/WNL.0000000000000692. Epub 2014 Jul 11.

19. Ding J, Sigurdsson S, Jonsson PV, et al. Space and location of cerebral microbleeds, cognitive decline, and dementia in the community. Neurology. 2017 May 30;88(22):2089-97. doi: 10.1212/WNL.0000000000003983. Epub 2017 May 3.

20. Romero JR, Preis SR, Beiser A, et al. Risk factors, stroke prevention treatments, and prevalence of cerebral microbleeds in the Framingham Heart Study. Stroke. 2014 May;45(5):1492-4. doi: 10.1161/STROKEAHA.114.004130. Epub 2014 Apr 8.

21. Wilson D, Ambler G, Shakeshaft C, et al. Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study. Lancet Neurol. 2018 Jun;17(6):539-47. doi: 10.1016/S1474-4422(18)30145-5. Epub 2018 May 16.

22. Lovelock CE, Cordonnier C, Naka H, et al. Antithrombotic drug use, cerebral microbleeds, and intracerebral hemorrhage: a systematic review of published and unpublished studies. Stroke. 2010 Jun;41(6):1222-8. doi: 10.1161/STROKEAHA.109.572594. Epub 2010 Apr 29.

23. Cheng Y, Wang Y, Song Q, et al. Use of anticoagulant therapy and cerebral microbleeds: a systematic review and meta-analysis. J Neurol. 2019 Oct 15. doi: 10.1007/s00415-019-09572-x

24. Soo Y, Abrigo J, Leung KT, et al. Correlation of non-vitamin K antagonist oral anticoagulant exposure and cerebral microbleeds in Chinese patients with atrial fibrillation. J Neurol Neurosurg Psychiatry. 2018 Jul;89(7):680-6. doi: 10.1136/jnnp-2017317151. Epub 2018 Mar 29.

25. Saito T, Kawamura Y, Sato N, et al. Nonvitamin K antagonist oral anticoagulants do not increase cerebral microbleeds. J Stroke Cerebrovasc Dis. 2015 Jun;24(6):1373-7. doi: 10.1016/j.jstrokecerebrovasdis.2015.02.018. Epub 2015 Apr 4.

26. Hagii J, Tomita H, Metoki N, et al. Characteristics of intracerebral hemorrhage during rivaroxaban treatment: comparison with those during warfarin. Stroke. 2014 Sep;45(9):2805-7. doi: 10.1161/STROKEAHA.114.006661. Epub 2014 Jul 31.

27. Michael N, Grigoryan MM, Kilday K, et al. Effects of dabigatran in mouse models of aging and cerebral amyloid angiopathy. Front Neurol. 2019 Sep 27;10:966. doi: 10.3389/fneur.2019.00966. eCollection 2019.

28. O'Donnell MJ, Eikelboom JW, Yusuf S, et al. Effect of apixaban on brain infarction and microbleeds: AVERROES-MRI assessment study. Am Heart J. 2016 Aug;178:145-50. doi: 10.1016/j.ahj.2016.03.019. Epub 2016 Apr 17.

29. Trial of Apixaban vs Warfarin in Reducing Rate of Cognitive Decline, Silent Cerebral Infarcts and Cerebral Microbleeds in Patients With Atrial Fibrillation (ARISTA). Available at:

30. Mongkhon P, Naser AY, Fanning L, et al. Oral anticoagulants and risk of dementia: A systematic review and meta-analysis of observational studies and randomized controlled trials. Neurosci Biobehav Rev. 2019 Jan;96:1–9. doi: 10.1016/j.neubiorev.2018.10.025. Epub 2018 Nov 2.

31. Cheng W, Liu W, Li B, Li D. Relationship of anticoagulant therapy with cognitive impairment among patients with atrial fibrillation: A meta-analysis and systematic Review. J Cardiovasc Pharmacol. 2018 Jun;71(6):380-7. doi: 10.1097/FJC.0000000000000575

32. Chen N, Lutsey PL, MacLehose RF, et al. Association of oral anticoagulant type with risk of dementia among patients with nonvalvular atrial fibrillation. J Am Heart Assoc. 2018 Nov 6;7(21):e009561. doi: 10.1161/JAHA.118.009561


For citations:

Ostroumova O.D., Kochetkov A.I., Ostroumova T.M. Atrial fibrillation and cognitive impairment: cerebral microbleeds as a new risk factor and possibilities of anticoagulant therapy (Part 2). Neurology, Neuropsychiatry, Psychosomatics. 2020;12(4):107-112. (In Russ.)

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