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The heterogeneity of vascular cognitive impairments and the issues of therapy

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Vascular cognitive impairments (CIs) are heterogeneous in the mechanism of their occurrence and may develop in different extent of brain damage, in different locations, and the number of foci. Their etiological factors are various. The mechanism for the development of CIs may be associated with impairments of both per se the structures responsible for cognitive functions (frontal cortex, subcortical-cortical interactions, and hippocampus) and deafferentation of the cortex and limbic structures due to periventricular white matter lesion or local lesion of the basal ganglia and thalamus. The pattern of CIs depends on the predominant involvement of cortical or subcortical regions or their combinations. The progression of CIs is also variable. In chronic cerebral circulatory insufficiency, CIs develop gradually over several years. Poststroke CIs manifest themselves acutely or subacutely. 6-27% of patients are diagnosed with dementia 3 months after acute cerebrovascular accident. The risk of subsequent dementia is 7% within the first year and 48% after 25 years.

The paper reviews the most important trials of citicoline used in CIs. The drug has a multicomponent activity spectrum that permits its use in CIs of varying genesis. By taking into account its good tolerability and safety, the drug may be recommended for a wide circle of patients, including for elderly patients with comorbidity.

About the Author

Elena Anatolyevna Katunina
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Russian Federation

Department of Neurology, Neurosurgery, and Medical Genetics,

1, Ostrovityanov St., Moscow 117997


1. Alzheimer's Association. Alzheimer's disease facts and figures. Alzheimers Dement. 2010 Mar;6(2):158-94. doi: 10.1016/j.jalz.2010.01.009.

2. World Population Ageing 2009, New York, NY, United Nations, 2009.

3. Ферстл Х, Мелике Ф, Вайхель К. Деменция. Москва: Медпресс-информ; 2011. 112 с. [Ferstl Kh, Melike A, Vaikhel' K. Dementsiya [Dementia]. Moscow: Medpressinform; 2011. 112 p.]

4. Fratiglioni L, Launer LJ, Andersen K, et al. Incidence of dementia and major subtypes in Europe: a collaborative study of populationbased cohorts. Neurologic Diseases in the Elderly Research Group. Neurology. 2000;54(11 Suppl 5):S10-5.

5. Akatsu H, Takahashi M, Matsukawa N, et al. Subtype analysis of neuropathologically diagnosed patients in a Japanese geriatric hospital. J Neurol Sci. 2002 Apr 15;196(1-2):63-9.

6. Alafuzoff I, Gelpi E, Al-Sarraj S, et al. The need to unify neuropathological assessments of vascular alterations in the ageing brain: multicentre survey by the BrainNet Europe consortium. Exp Gerontol. 2012 Nov;47(11):825-33. doi:10.1016/j.exger.2012.06.001. Epub 2012 Jun 15.

7. Hachinski V, Iadecola C, Petersen RC, et al. National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards. Stroke. 2006 Sep;37(9):2220-41. Epub 2006 Aug 17.

8. Attems J, Jellinger K, Thal DR, Van Nostrand W. Review: sporadic cerebral amyloid angiopathy. Neuropathol Appl Neurobiol. 2011 Feb;37(1):75-93. doi: 10.1111/j.1365-2990.2010.01137.x.

9. Ferrer I. Cognitive impairment of vascular origin: neuropathology of cognitive impairment of vascular origin. J Neurol Sci. 2010 Dec 15;299(1-2):139-49. doi: 10.1016/j.jns.2010.08.039. Epub 2010 Sep 16.

10. Liberato B, Chong JY, Sacco RL. Focal brain ischemia. Clinical features, epidemiology, risk factors and outcome, in Cerebrovascular Diseases, Kalimo H, editor. Basel: ISN Neuropath Press; 2005. P. 176-85.

11. Grinberg LT, Thal DR. Vascular pathology in the aged human brain. Acta Neuropathol. 2010 Mar;119(3):277-90. doi: 10.1007/s00401-010-0652-7. Epub 2010 Feb 14.

12. Thal DR, Ghebremedhin E, Orantes M, Wiestler OD. Vascular pathology in Alzheimer disease: correlation of cerebral amyloid angiopathy and arteriosclerosis/lipohyalinosis with cognitive decline. J Neuropathol Exp Neurol. 2003 Dec;62(12):1287-301.

13. Vinters HV, Ellis WG, Zarow C, et al. (2000).Neuropathologic substrates of ischemic vascular dementia. J Neuropathol Exp Neurol. 2000 Nov;59(11):931-45.

14. Grinberg LT, Thal DR. Vascular pathology in the aged human brain. Acta Neuropathol. 2010 Mar;119(3):277-90. doi: 10.1007/s00401-010-0652-7. Epub 2010 Feb 14.

15. Giannakopoulos P, Gold G, Kovari E, et al. (2007). A ssessing the cognitive impact of Alzheimer disease pathology and vascular burden in the aging brain: the Geneva experience. Acta Neuropathol. 2007 Jan;113(1):1-12. Epub 2006 Oct 12.

16. Jellinger KA. Pathology and pathogenesis of vascular cognitive impairment – a critical update. Front Aging Neurosci. 2013 Apr 10;5:17. doi: 10.3389/fnagi.2013.00017. eCollection 2013.

17. Attems J, Jellinger K, Thal DR, Van Nostrand W. Review: sporadic cerebral amyloid angiopathy. Neuropathol Appl Neurobiol. 2011 Feb;37(1):75-93. doi: 10.1111/j.1365-2990.2010.01137.x.

18. Jellinger KA. Alzheimer disease and cerebrovascular pathology: an update. J Neural Transm. 2002 May;109(5-6):813-36.

19. Okamoto Y, Yamamoto T, Kalaria RN, et al. Cerebral hypoperfusion accelerates cerebral amyloid angiopathy and promotes cortical microinfarcts. Acta Neuropathol. 2012 Mar;123(3):381-94. doi: 10.1007/s00401-011-0925-9. Epub 2011 Dec 15.

20. Thal DR, Capetillo-Zarate E, Larionov S, et al. Capillary cerebral amyloid angiopathy is associated with vessel occlusion and cerebral blood flow disturbances. Neurobiol Aging. 2009 Dec;30(12):1936-48. doi: 10.1016/j.neurobiolaging.2008.01.017. Epub 2008 Mar 21.

21. Revesz T, Holton JL, Lashley T, et al. (2009). Genetics and molecular pathogenesis of sporadic and hereditary cerebral amyloid angiopathies. Acta Neuropathol. 2009 Jul;118(1):115-30. doi: 10.1007/s00401-009-0501-8. Epub 2009 Feb 19.

22. Jellinger KA. The enigma of vascular cognitive disorder and vascular dementia. Acta Neuropathol. 2007 Apr;113(4):349-88. Epub 2007 Feb 7.

23. Arvanitakis Z, Leurgans SE, Wang Z, et al. Cerebral amyloid angiopathy pathology and cognitive domains in older persons. Ann Neurol. 2011 Feb;69(2):320-7. doi: 10.1002/ana.22112. Epub 2010 Nov 8.

24. Pfeifer LA, White LR, Ross GW, et al. Cerebral amyloid angiopathy and cognitive function: the HAAS autopsy study. Neurology. 2002 Jun 11;58(11):1629-34.

25. Johnson KA, Gregas M, Becker JA, et al. Imaging of amyloid burden and distribution in cerebral amyloid angiopathy. Ann Neurol. 2007 Sep;62(3):229-34.

26. Ly JV, Donnan GA, Villemagne VL, et al. 11C-PIB binding is increased in patients with cerebral amyloid angiopathy-related hemorrhage. Neurology. 2010 Feb 9;74(6):487-93. doi: 10.1212/WNL.0b013e3181cef7e3.

27. Viswanathan A, Godin O, Jouvent E, et al. Impact of MRI markers in subcortical vascular dementia: a multi-modal analysis in CADASIL. Neurobiol Aging. 2010 Sep;31(9):1629-36. doi: 10.1016/j.neurobiolaging.2008.09.001. Epub 2008 Oct 15.

28. Joutel A, Dodick DD, Parisi JE, et al. De novo mutation in the Notch3 gene causing CADASIL. Ann Neurol. 2000 Mar;47(3):388-91.

29. Malandrini A, Gaudiano C, Gambelli S, et al. Diagnostic value of ultrastructural skin biopsy studies in CADASIL. Neurology. 2007 Apr 24;68(17):1430-2.

30. Gregoire SM, Smith K, Jager HR, et al. Cerebral microbleeds and long-term cognitive outcome: longitudinal cohort study of stroke clinic patients. Cerebrovasc Dis. 2012;33(5):430-5. doi: 10.1159/000336237. Epub 2012 Mar 28.

31. Qiu C, Cotch MF, Sigurdsson S, et al. Cerebral microbleeds, retinopathy, and dementia: the AGES-Reykjavik Study. Neurology. 2010 Dec 14;75(24):2221-8. doi: 10.1212/WNL.0b013e3182020349.

32. Poels MM, Ikram MA, van der Lugt A, et al. Cerebral microbleeds are associated with worse cognitive function: the Rotterdam Scan Study. Neurology. 2012 Jan 31;78(5):326-33. doi: 10.1212/WNL.0b013e3182452928. Epub 2012 Jan 18.

33. Farkas E, de Vos RA, Donka G, et al. (2006). Age-related microvascular degeneration in the human cerebral periventricular white matter. Acta Neuropathol. 2006 Feb;111(2): 150-7. Epub 2006 Feb 2.

34. Ince P. Acquired forms of vascular dementia. In Cerebrovascular Diseases. Kalimo H, editor. Basel: ISN Neuropath Press; 2005. P. 316-23.

35. Elbaz A, Vicente-Vytopilova P, Tavernier B, et al. Motor function in the elderly: evidence for the reserve hypothesis. Neurology. 2013 Jul 30;81(5):417-26. doi: 10.1212/WNL.0b013e31829d8761. Epub 2013 Jun 26.

36. O'Donnell MJ, Xavier D, Liu L, et al. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study. Lancet. 2010 Jul 10;376(9735):112-23. doi: 10.1016/S0140-6736(10)60834-3. Epub 2010 Jun 17.

37. Singh-Manoux A, Marmot MG, Glymour M, et al. Does cognitive reserve shape cognitive decline? Ann Neurol. 2011 Aug;70(2):296-304. doi: 10.1002/ana.22391. Epub 2011 May 11.

38. Rist PM, Chalmers J, Arima H, et al. Baseline cognitive function, recurrent stroke, and risk of dementia in patients with stroke. Stroke. 2013 Jul;44(7):1790-5. doi: 10.1161/STROKEAHA.111.680728. Epub 2013 May 16.

39. Yip AG, McKee AC, Green RC, et al. (2005). APOE, vascular pathology, and the AD brain. Neurology. 2005 Jul 26;65(2):259-65.

40. Baum L, Lam LC, Kwok T, et al. (2006). Apolipoprotein E epsilon 4 allele is associated with vascular dementia. Dement. Dement Geriatr Cogn Disord. 2006;22(4):301-5. Epub 2006 Aug 22.

41. Tomlinson BE, Blessed G, Roth M. Observations on the brains of demented old people. J Neurol Sci. 1970 Sep;11(3):205-42.

42. Zekry D, Duyckaerts C, Belmin J, et al. The vascular lesions in vascular and mixed dementia: the weight of functional neuroanatomy. Neurobiol Aging. 2003 Mar-Apr;24(2):213-9.

43. Vinters HV, Ellis WG, Zarow C, et al. (2000). Neuropathologic substrates of ischemic vascular dementia. J Neuropathol Exp Neurol. 2000 Nov;59(11):931-45.

44. del Ser T, Hachinski V, Merskey H, Munoz DG. (2005). Alzheimer's disease with and without cerebral infarcts. J Neurol Sci. 2005 Apr 15;231(1-2):3-11. Epub 2004 Dec 29.

45. Jellinger KA, Attems J. (2005). Prevalence and pathogenic role of cerebrovascular lesions in Alzheimer's disease. J Neurol Sci. 2005 Mar 15;229-230:37-41. Epub 2004 Dec 22.

46. Attems J, Konig C, Huber M, et al. Cause of death in demented and non-demented elderly inpatients; an autopsy study of 308 cases. J Alzheimers Dis. 2005 Sep;8(1):57-62.

47. Lo RY, Jagust WJ. Vascular burden and Alzheimer disease pathologic progression. Neurology. 2012 Sep 25;79(13):1349-55. Epub 2012 Sep 12.

48. Lewis H, Beher D, Cookson N, et al. (2006). Quantification of Alzheimer pathology in ageing and dementia: age-related accumulation of amyloid-beta(42) peptide in vascular dementia. Neuropathol Appl Neurobiol. 2006 Apr;32(2):103-18.

49. Kokmen E, Whisnant JP, O'Fallon WM, et al. Dementia after ischemic stroke: a populationbased study in Rochester, Minnesota (1960-1984). Neurology. 1996 Jan;46(1):154-9.

50. Zhao QL, Zhou Y, Wang YL, et al. (2010). A new diagnostic algorithm for vascular cognitive impairment: the proposed criteria and evaluation of its reliability and validity. Chin Med J (Engl). 2010 Feb 5;123(3):311-9.

51. Gorelick PB, Scuteri A, Black SE, et al. (2011). Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association. Stroke. 2011 Sep;42(9):2672-713. doi: 10.1161/STR.0b013e3182299496. Epub 2011 Jul 21.

52. Bacchetta JP, Kovari E, Merlo M, et al. (2007). Validation of clinical criteria for possible vascular dementia in the oldest-old. Neurobiol. Neurobiol Aging. 2007 Apr;28(4):579-85. Epub 2006 Mar 31.

53. Reed BR, Mungas DM, Kramer JH, et al. Profiles of neuropsychological impairment in autopsy-defined Alzheimer's disease and cerebrovascular disease. Brain. 2007 Mar;130 (Pt 3):731-9. Epub 2007 Jan 31.

54. Gainotti G, Ferraccioli M, Vita MG, Marra C. Patterns of neuropsycho-logical impairment in MCI patients with small subcortical infarcts or hippocampal atrophy. J Int Neuropsychol Soc. 2008 Jul;14(4):611-9. doi: 10.1017/S1355617708080831.

55. Tomlinson BE, Blessed G, Roth M. Observations on the brains of demented old people. J Neurol Sci.1970;11:205-242.

56. Kalaria RN, Kenny RA, Ballard CG, et al. Towards defining the neuropathological substrates of vascular dementia. J Neurol Sci. 2004 Nov 15;226(1-2):75-80.

57. Dаvalos A, Castillo J, Alvarez-Sabin J, et al. A meta-analysis has suggested a mild benefit for citicoline. Stroke. 2002 Dec;33(12):2850-7.

58. Приказ Минздрава РФ от 29 декабря 2012 г. N 1740н «Об утверждении стандарта специализированной медицинской помощи при инфаркте мозга» [Prikaz Minzdrava RF ot 29 dekabrya 2012 g. N 1740n «Ob utverzhdenii standarta spetsializirovannoi meditsinskoi pomoshchi pri infarkte mozga»].

59. Diederich K, Frauenknecht K, Minnerup J, et al. Citicoline Enhances Neuroregenerative Processes After Experimental Stroke in Rats. Stroke. 2012 Jul;43(7):1931-40. doi: 10.1161/STROKEAHA.112.654806. Epub 2012 May 10.

60. Gutierrez-Fernandez M, Rodriguez-Frutos B, Fuentes B, et al. CDP-choline treatment induces brain plasticity markers expression in experimental animal stroke. Neurochem Int. 2012 Feb;60(3):310-7. doi: 10.1016/j.neuint.2011.12.015. Epub 2011 Dec 30.

61. 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.

62. Agnoli A, Bruno G, Fioravanti M. Therapeutic approach to senile memory impairment: a double-blind clinical trial with CDP choline. In: Wurtman RJ, Corkin S, Growden JH, editors. Alzheimer's Disease: Proceedings of the Fifth Meeting of the International Study Group on the Pharmacology of Memory Disorders Associated with Aging. Boston, MA: Birkhauser; 1989. P. 649-54.

63. Spiers PA, Myers D, Hochanadel GS, et al. Citicoline improves verbal memory in aging. Arch Neurol. 1996 May;53(5):441-8.

64. Milani M. Citicoline as coadiuvant treatment of cognitive impairment in chronic degenerative Central Nervous System diseases and in ischemic stroke: A review of available data. Online Journal of Medicine and Medical Science Research. 2013;2(2):13-8.

65. Alvarez XA, Mouzo R, Pichel V, et al. Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer's disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion. Methods Find Exp Clin Pharmacol. 1999 Nov;21(9):633-44.

66. Franco-Maside A, Caamano J, Gomez MJ, Cacabelos R. Brain mapping activity and mental performance after chronic treatment with CDP-choline in Alzheimer's disease. Methods Find Exp Clin Pharmacol. 1994 Oct;16(8):597-607.

67. Fernandez-Novoa L, Alvarez XA, Franco-Maside A, et al. CDP-choline-induced blood histamine changes in Alzheimer's disease. Methods Find Exp Clin Pharmacol. 1994 May;16(4):279-84.

68. Пирадов МА, Сергеев ДВ, Кротенкова МВ. Применение Цераксона в остром периоде полушарного ишемического инсульта: клиническая и КТ-перфузионная оценка. Анналы клинической и экспериментальной неврологии. 2012;6(3):31-7. [Piradov MA, Sergeev DV, Krotenkova MV. The use of Ceraxon in the acute period of hemispheric ischemic stroke: clinical and CT perfusion assessment. Annaly klinicheskoi i eksperimental'noi nevrologii. 2012;6(3):31-7. (In Russ.)].

69. Гаврилова СИ, Федорова ЯБ. Цераксон (цитиколин) в лечении синдрома мягкого когнитивного снижения. Журнал неврологии и психиатрии им. С.С. Корсакова. 2011; (12):17-20. [Gavrilova SI, Fedorova YaB. Ceraxon (citicoline) in the treatment of the syndrome of mild cognitive decline. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2011;(12):17-20. (In Russ.)].

70. Alvarez-Sabin J, Roman GC. Citicoline in vascular cognitive impairment and vascular dementia after stroke. Stroke. 2011 Jan;42 (1 Suppl):S40-3. doi: 10.1161/STROKEAHA.110.606509. Epub 2010 Dec 16.

71. Lozano R. Efficacy and safety of oral CDP-choline. Drug surveillance study in 2817 cases. Arzneimittelforschung. 1983;33(7A):1073-80.

72. 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. Epub 2013 Feb 7.

For citation:

Katunina E.A. The heterogeneity of vascular cognitive impairments and the issues of therapy. Neurology, Neuropsychiatry, Psychosomatics. 2015;7(3):62-69. (In Russ.)

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