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Dementia due to cerebral small vessel damage: Current ideas on its pathogenesis and therapy

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Ever-increasing attention now focusses on dementia caused by small vessel damage when considering cerebrovascular disease leading to cognitive impairments (CIs). Stroke is one of the most important risk factors (RFs) of vascular CI, including vascular dementia. Experienced stroke increases thrice the risk of dementia. Diffuse changes in the cerebral white matter (leukoaraiosis) due to fluctuating blood pressure (BP) and cerebral small vessel damage in most cases play an important role in the genesis of vascular CIs. Executive dysfunctions frequently concurrent with delayed psychomotor speed are the leading clinical manifestations of subcortical vascular dementia. Severe memory impairments are not
typical for subcortical dementia, its early stages in particular. The basis for the pathogenesis of CIs is the dissociation phenomenon that disrupts connections between the frontal lobes and subcortical structures and other cerebral cortical areas. Inadequate hypertension correction at a middle age is responsible for more than one fourth of cases of dementia developing in the elderly. The detection and further elimination of vascular RFs can reduce the risk of developing dementia in elderly and senile patients. Correction of elevated BP in the middle-aged is regarded as an effective method to prevent dementia in the future, but no premium is placed upon antihypertensive therapy in the elderly to lower elevated BP that is an inherent characteristic of this category of patients. Medications affecting RFs and those improving cerebral metabolism and blood
flow, including nicergoline are widely used to treat PD.

About the Authors

I. V. Damulin
Department of Nervous System Diseases and Neurosurgery, Faculty of Therapeutics I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow, Russia 11, Rossolimo St., Moscow 119021
Russian Federation

E. V. Ekusheva
Reseach Department of Neurology, Research Center, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow, Russia 11, Rossolimo St., Moscow 119021
Russian Federation


1. Kuller LH, Lopez OL, Jagust WJ, et al. Determinants of vascular dementia in the Cardiovascular Health Cognition Study. Neurology. 2005;64:1548–52. DOI: 0000160115.55756.DE.

2. Tullberg M, Fletcher E, DeCarli C, et al. White matter lesions impair frontal lobe function regardless of their location. Neurology. 2004;63:246–53. DOI:

3. Kaffashian S, Dugravot A, Brunner EJ, et al. Midlive stroke risk and cognitive decline: a 10-year follow-up of the Whitehall II cohort study. Alzheim Dement. 2013;9:572–9. DOI:

4. Cumming TB, Marshall RS, Lazar RM. Stroke, cognitive deficits, and rehabilitation: still an incomplete picture. Int J Stroke.2013;8:38–45. DOI:

5. De Haan EH, Nys GM, van Zandvoort MJ. Cognitive function following stroke and vascular cognitive impairment. Curr Opin Neurol. 2006;19:559–64. DOI:

6. Murphy TH, Corbett D. Plasticity during stroke recovery: from synapse to behaviour. Nature Rev Neurosci. 2009;10:861–72. DOI:

7. Vermeer SE, Prins ND, den Heijer T, et al. Silent brain infarcts and the risk of dementia and cognitive decline. New Engl J Med. 2003;348:1215–22. DOI:

8. Fein G, Di Sclafani V, Tanabe J, et al. Hippocampal and cortical atrophy predict dementia in subcortical ischemic vascular disease. Neurology. 2000;55:1626–35. DOI:

9. Blass JP, Ratan RR. «Silent» strokes and dementia. New Engl J Med. 2003;348(13): 1277–8. DOI:

10. Werring DJ, Coward LJ, Losseff NA, et al. Cerebral microbleeds are common in ischemic stroke but rare in TIA. Neurology. 2005;65:1914–8. DOI: 1212/01.wnl.0000188874.48592.f7.

11. Wardlaw JM. What causes lacunar stroke? J Neurol Neurosurg Psychiatry. 2005;76:617–9. DOI:

12. Alexander MP, Stuss DT. Disorders of frontal lobe functioning. Sem Neurol. 2000;20(40):427–37. DOI:

13. Kwan LT, Reed BR, Eberling JL, et al. Effects of subcortical cerebral infarction on cortical glucose metabolism and cognitive function. Arch Neurol. 1999;56:809–14. DOI:

14. Reed BR, Eberling JL, Mungas D, et al. Effects of white matter lesions and lacunes on cortical function. Arch Neurol. 2004;61:1545–50. DOI: 61.10.1545.

15. Reed BR, Eberling JL, Mungas D, et al. Frontal lobe hypometabolism predicts cognitive decline in patients with lacunar infarctions. Arch Neurol. 2001;58:494–7. DOI:

16. De Leeuw FE, van Gijn J. Vascular dementia. Pract Neurol. 2003;3:86–91. DOI:

17. Walha K, Ricolfi F, Bejot Y, et al. Hippocampus: a «forgotten» border zone of brain ischemia. J Neuroimag. 2013;23:98–101. DOI:

18. Charidimoi A, Krishnan A, Werring DJ, Jager HR. Cerebral microbleedings: a guide to detection and clinical relevance in different disease settings. Neuroradiol. 2013;55:655–74. DOI:

19. Cordonnier C. Brain microbleedens: more evidence, but still a clinical dilemma. Curr Opin Neurol. 2011;24:69–74. DOI:

20. De Leeuw FE, de Groot JC, Oudkerk M, et al. Hypertension and cerebral white matter lesions in a prospective cohort study. Brain. 2002;125:765–72. DOI: 10.1093/brain/awf07721.

21. Goldstein IB, Bartzokis G, Guthrie D, Shapiro D. Ambulatory blood pressure and the brain. A 5-year follow-up. Neurology. 2005;64:1846–52. DOI:

22. Bonoczk P, Panczel G, Nagy Z. Vasoreactivity in patients with periventricular white matter lucency. Acta Neurologica Scand. 2004;110 (4): 254–6. DOI:

23. Pantoni L, Poggesi A, Inzitari D. The relation between white-matter lesions and cognition. Curr Opin Neurol. 2007;20:390–7. DOI:

24. Udaka F, Sawada H, Kameyama M. White matter lesions and dementia: MRI-pathologicalcorrelations. Ann NY Acad Sci. 2002;977:411–5. DOI:

25. Guermazi A, Miaux Y, Rovira-Canellas A, et al. Neuroradiological findings in vascular dementia. Neuroradiol. 2007;49:1–22. DOI:

26. Yamauchi H. Ischemic white matter damage and cognitive impairment. Psychogeriatrics. 2003;3:11–6. DOI: 1046/j.1479-8301.2003.00003.x.

27. Kril JJ, Patel S, Harding AJ, Halliday GM. Patients with vascular dementia due to microvascular pathology have significant hippocampal neuronal loss. J Neurol Neurosurg Psychiatry. 2002;72:747–51. DOI:

28. Righart R, Duering M, Gonik M, et al. Impact of regional cortical and subcortical changes on processing speed in cerebral small vessel disease. Neuroimage Clin. 2013;2:854–61. DOI: 06.006.

29. Capizzano AA, Schuff N, Amend DL, et al. Subcortical ischemic vascular dementia: assessment with quantitative MR imaging and 1H MR spectroscopy. Am J Neuroradiol. 2000;21(4):621–30.

30. Greener M. Clarifying the link between Alzheimer's and vascular disease. Progress in Neurology and Psychiatry. 2013;March/April:27–8. DOI:

31. Benarroch EE. Microglia: Multiple roles in surveillance, circuit shaping, and response to injury. Neurology. 2013;81:1079–88. DOI:

32. Meyer JS, Xu G, Thornby G, et al. Is mild cognitive impairment prodromal for vascular dementia like Alzheimer's disease? Stroke. 2002;33:1981–5. DOI: 1161/01.STR.0000024432.34557.10.

33. Poels MMF, Steyerberg EW, Wieberdink RG, et al. Assessment of cerebral small vessel disease predicts individual stroke risk. J Neurol Neurosurg Psychiatry. 2012;83:1174–9. DOI:

34. Elkins JS, O'Meara ES, Longstreth WT, et al. Stroke risk factors and loss of high cognitive function. Neurology. 2004;63:793–9.DOI: 0000137014.36689.7F.

35. Imfeld P, Bodmer M, Schuerch M, et al. Risk of incident stroke in patients with Alzheimer disease or vascular dementia. Neurology. 2013;81:910–9. DOI:

36. Вахнина НВ. Сосудистые когнитивные нарушения. Неврологuя, нейропсихиатрия, психосоматика. 2014;(1):74–9. [Vakhnina NV. Vascular cognitive impairment. Nevrologuya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2014;(1):74–9. (In Russ.)]. DOI:

37. Stewart R. Vascular dementia: a diagnosis running out of time. Br J Psychiatry. 2002;180:152–6. DOI: 1192/bjp.180.2.152

38. Sachdev PS, Brodaty H, Valenzuela MJ, et al. The neuropsychological profile of vascular cognitive impairment in stroke and TIA patients. Neurology. 2004;62:912–9. DOI: 0000115108.65264.4B.

39. Alvarez JA, Emory E. Executive function and the frontal lobes: a meta-analytic review. Neuropsychol Rev. 2006;16(1):17–42. DOI:

40. Jurado MB, Rosselli M. The elusive nature of executive functions: a review of our current understanding. Neuropsychol Rev. 2007;17:213–33. DOI: 10.1007/s11065-007-9040-z41.

41. Nachev P. Cognition and medial frontal cortex in health and disease. Curr Opin Neurol. 2006;19:586–92. DOI: 1097/

42. Cummings JL, Trimble MR. Concise guide to neuropsychiatry and behavioral neurology. 2nd ed. Washington, London: American Psychiatric Publishing, Inc.; 2002. 275 p.

43. Della Sala S, Gray C, Spinnler H, Trivelly C. Frontal lobe function in man: the riddle revisited. Arch Clin Neuropsychol. 1998;13(8):663–82.

44. Nonaka H, Akima M, Hatori T, et al. Microvasculature of the human cerebral white matter: Arteries of the deep white matter. Neuropathology. 2003;23:111–8. DOI:

45. Hirono N, Kitagaki H, Kazui H, et al. Impact of white matter changes on clinical manifestation of Alzheimer's disease: a quantitative study. Stroke. 2000;31:2182–8. DOI:

46. Oostrman JM, de Vries K, Scherder EJA. Executive ability in relation to blood pressure in residents of homes for the elderly. Arch Clinic Neuropsychol. 2007;22:731–8. DOI:

47. Den Heijer T, Launer LJ, Prins ND, et al. Association between blood pressure, white matter lesions, and atrophy of the medial temporal lobe. Neurology. 2005;64:263–7. DOI: 0000149641.55751.2E.

48. Gelber RP, Ross GW, Petrovitch H, et al.Antihypertensive medication use and risk of cognitive impairment: the Honolulu-Asia Aging Study. Neurology. 2013;81:888–95. DOI: 0b013e3182a351d4.

49. Alagiakrishnan K, McCracken P, Feldman H. Treating vascular risk factors and maintaining vascular health: Is this the way towards successful cognitive ageing and preventing cognitive decline? Postgrad Med J. 2006; 82:101–5. DOI:

50. Seshadri S. Delaying dementia: can antihypertensives prevent Alzheimer dementia? Neurology. 2013;81:860–2. DOI: 0b013e3182a35296.

51. Hill MD, Mitchell JR. White matter lesions and cognition. It's time for randomized trials to preserve intelligence. Neurology. 2006;66:470–1. DOI:

52. Staessen JA, Gasowski J, Wang JG, et al. Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials. Lancet. 2000;355(9207):865–72. DOI:

53. Feigin V, Ratnasabapathy Y, Anderson C. Does blood pressure lowering treatment prevents dementia or cognitive decline in patients with cardiovascular and cerebrovascular disease? J Neurol Sci. 2005;229–230:151–5. DOI:

54. Pandita-Gunawardena ND, Clarke SEM. Amlodipine lowers blood pressure without affecting cerebral blood flow as measured by single photon emission computed tomography in elderly hypertensive subjects. Age Ageing. 1999;28:451–7. DOI:

55. Calero MD, Navarro E. Relationship between plasticity, mild cognitive impairment and cognitive decline. Arch Clin Neuropsychol. 2004;19:653–60. DOI:

56. Farfel JM, Nitrini R, Suemoto CK, et al. Very low levels of education and cognitive reserve: a clinicopathologic study. Neurology. 2013;81:650–7. DOI:

57. Преображенская ИС. Деменция – эпидемиология, клиническая картина, диагностика, подходы к терапии. Неврология, нейропсихиатрия, психосоматика. 2013;(4):71–7. [Preobrazhenskaya IS. Dementia: epidemiology, clinical picture, diagnosis, approaches to therapy. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2013;(4):71–7. (In Russ.)]. DOI: 14412/2074-2711-2013-2459.

58. Van Spronsen M, Hoogenraad C. Synapse pathology in psychiatric and neurologic disease. Curr Neurol Neurosci Rep. 2010;10:207–14. DOI:

59. Максимова МЮ, Домашенко МА, Танашян ММ. Современные подходы к профилактике и лечению хронических нарушений мозгового кровообращения. Неврология, нейропсихиатрия, психосоматика. 2012;(4):88–91. [Maksimova MYu, Domashenko MA, Tanashyan MM. Current approaches to preventing and treating chronic cerebral circulatory disorder. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2012;(4):88–91. (In Russ.)].

60. DOI:

61. Парфенов ВА. Антигипертензивная терапия в профилактике инсульта и когнитивных расстройств. Неврологический журнал. 2006;11(4):31–5. [Parfenov VA. Antihipertensiv

62. therapy in prevention of a stroke and cognitive frustration. Nevrologicheskii zhurnal. 2006;11(4):31–5. (In Russ.)]

63. Стаховская ЛВ, Скворцова ВИ, Чазова ИЕ. Вторичная профилактика ишемического инсульта. Consilium Medicum. 2003;5(8):473–6. [Stakhovskaya LV, Skvortsova VI, Chazova IE. Secondary prevention of an ischemic stroke. Consilium Medicum. 2003;5(8):473–6. (In Russ.)]

64. Gould DB, Phalan FC, van Mil SE, et al. Role of COL4A1 in small-vessel disease and hemorrhagic stroke. New Engl J Med. 2006;354(14):1489–96. DOI:

65. Greenberg SM. Small vessels, big problems. New Engl J Med. 2006;354(14):1451–3. DOI:

66. Vahedi K, Boukobza M, Massin P, et al. Clinical and brain MRI follow-up study of a family with COL4A1 mutation. Neurology. 2007;69:1564–8. DOI:

67. Hassan A, Hunt BJ, O'Sullivan M, et al. Markers of endothelial dysfunction in lacunar infarction and ischaemic leukoaraiosis. Brain. 2003;126(2):424–32. DOI:

68. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomized trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Br Med J. 2002;324:71–86. DOI:

69. Winblad B, Carfagna N, Bonura L, et al. Nicergoline in dementia. A review of its pharmacological properties and therapeutic potential. CNS Drugs. 2000;14:267–87. DOI:

70. Winblad B, Fioravanti M, Dolezal T, et al. Therapeutic use of nicergoline. Clin Drug Invest. 2008;28:533–52. DOI:

71. Cattabeni F. Protein kinase C in synaptic plasticity: A molecular target in the treatment of cognitive disorders. Dement Geriatr Cogn Disord. 1997;8 Suppl 1:6–11.

72. Одинак ММ, Емелин АЮ, Лобзин ВЮ. Нарушения когнитивных функций при цереброваскулярной патологии. Санкт-Петербург: ВМедА; 2006. 158 с. [Odinak MM, Emelin AYu,

73. Lobzin VYu. Narusheniya kognitivnykh funktsii pritserebrovaskulyarnoi patologii [Violations of cognitive functions at cerebrovasculyar pathology] . St-Petersburg: VMedA; 2006. 158 p.]

74. Caraci F, Chisari M, Frasca G, et al. Nicergoline, a drug used for age-dependent cognitive impairment, protects cultured neurons against β-amyloid toxicity. Brain Res. 2005;1047:30–7.

75. DOI: 2005.04.004.

76. Giardino L, Giuliani A, Battaglia A, et al. Neuroprotection and aging of the cholinergic system: A role for the ergoline derivative nicergoline (Sermion). Neurosci. 2002;109:487–97.

77. DOI:

78. Crook TH. Nicergoline: Parallel evolution of clinical trial methodology and drug development in dementia. Dement Geriatr Cogn Disord. 1997;8 Suppl 1:22–6. DOI:

For citation:

Damulin I.V., Ekusheva E.V. Dementia due to cerebral small vessel damage: Current ideas on its pathogenesis and therapy. Neurology, Neuropsychiatry, Psychosomatics. 2014;6(4):94-100. (In Russ.)

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