The ClinicianThe ClinicianКлиницист1818-83382412-8775Publishing House ABV Press17710.17650/1818-8338-2015-1-18-23REVIEWОБЗОРCOGNITIVE IMPAIRMENTS IN VITAMIN B12 AND FOLIC ACID DEFICIENCIES AND HYPERHOMOCYSTEINEMIAКОГНИТИВНЫЕ НАРУШЕНИЯ ПРИ ДЕФИЦИТЕ ВИТАМИНА В12, ФОЛИЕВОЙ КИСЛОТЫ И ГИПЕРГОМОЦИСТЕИНЕМИИKamchatnovP. R.КамчатновП. Р.Russian Federationpavkam7@gmail.comDamulinI. V.ДамулинИ. В.Russian FederationDepartment of Neurology, Neurosurgery, and Medical Genetics, Faculty of Therapeutics, N.I. Pirogov Russian National Research Medical University, Ministry of Health of RussiaКафедра неврологии, нейрохирургии и медицинской генетики лечебного факультета ГБОУ ВПО РНИМУ им. Н.И. Пирогова Минздрава России1 Ostrovityanovа St., Moscow, 117997, RussiaРоссия, 117997, Москва, ул. Островитянова, 1Department of Nervous System Diseases, and Neurosurgery, Faculty of Therapeutics, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russiaкафедра нервных болезней и нейрохирургии лечебного факультета ГБОУ ВПО Первый МГМУ им. И.М. Сеченова Минздрава России2 Bld. 4 Bolshaya Pirogovskaya St., Moscow, 119991, RussiaРоссия, 119991, Москва, ул. Большая Пироговская, 2, стр. 4150120159118231505201515052015Copyright ©; 2015, Kamchatnov P.R., Damulin I.V.Copyright ©; 2015, Камчатнов П.Р., Дамулин И.В.2015Kamchatnov P.R., Damulin I.V.Камчатнов П.Р., Дамулин И.В.https://creativecommons.org/licenses/by/4.0https://klinitsist.abvpress.ru/Klin/article/view/177Alzheimer’s diseasedementiacobalamin deficiencyfolic acid deficiencyhyperhomocysteinemiahomocysteineischemic stroketreatmentinflammatory markerspyridoxineelderly patientpreventiontransient ischemic attackfolic acidcyanocobalamiболезнь Альцгеймерадеменциядефицит кобаламинадефицит фолиевой кислотыгипергомоцистеинемиягомоцистеинишемический инсультлечениемаркеры воспаленияпиридоксинпожилой больнойпрофилактикатранзиторная ишемическая атакафолиевая кисл[1. Woo K.S., Kwok T.C., Celermajer D.S. Vegan diet, subnormal vitamin B-12 status and cardiovascular health. Nutrients 2014;6(8):3259–73.Woo K.S., Kwok T.C., Celermajer D.S. Vegan diet, subnormal vitamin B-12 status and cardiovascular health. Nutrients 2014;6(8):3259–73.][2. Robins Wahlin T.B., Wahlin A., Winblad B., Bäckman L. The influence of serum vitamin B12 and folate status on cognitive functioning in very old age. Biol Psychol 2001;56(3): 247–65.Robins Wahlin T.B., Wahlin A., Winblad B., Bäckman L. The influence of serum vitamin B12 and folate status on cognitive functioning in very old age. Biol Psychol 2001;56(3): 247–65.][3. Greenberg D.A., Aminoff M.J., Simon R.P. Clinical Neurology. 5th ed. New York: McGraw-Hill Professional, 2012.Greenberg D.A., Aminoff M.J., Simon R.P. Clinical Neurology. 5th ed. New York: McGraw-Hill Professional, 2012.][4. Perkin G.D., Murray-Lyon I. Neurology and the gastrointestinal system. J Neurol Neurosurg Psychiatry 1998;65(3):291–300.Perkin G.D., Murray-Lyon I. Neurology and the gastrointestinal system. J Neurol Neurosurg Psychiatry 1998;65(3):291–300.][5. Clark C.M. Metabolic and nutritional disorders associated with dementia. In: J.C. Morris, J.E. Galvin, D.M. Holzman (eds.). Handbook of Dementing Illnesses. New York: Marcel Dekker, Inc., 1994. Рp. 413–39.Clark C.M. Metabolic and nutritional disorders associated with dementia. In: J.C. Morris, J.E. Galvin, D.M. Holzman (eds.). Handbook of Dementing Illnesses. New York: Marcel Dekker, Inc., 1994. Рp. 413–39.][6. Wahlund L.O., Basun H., Waldemar G. Reversible or arrestable dementias. In: N. Qizilbash et al. (eds.). Evidence-based Dementia Practice. Oxford: Blackwell Sciences, 2002. Рр. 330–40.Wahlund L.O., Basun H., Waldemar G. Reversible or arrestable dementias. In: N. Qizilbash et al. (eds.). Evidence-based Dementia Practice. Oxford: Blackwell Sciences, 2002. Рр. 330–40.][7. Abyad A. Prevalence of vitamin B12 deficiency among demented patients and cognitive recovery with cobalamin replacement. J Nutr Health Aging 2002;6(4):254–60.Abyad A. Prevalence of vitamin B12 deficiency among demented patients and cognitive recovery with cobalamin replacement. J Nutr Health Aging 2002;6(4):254–60.][8. Rietsema W.J. Unexpected recovery of moderate cognitive impairment on treatment with oral methylcobalamin. J Am Geriatr Soc 2014;62(8):1611–2.Rietsema W.J. Unexpected recovery of moderate cognitive impairment on treatment with oral methylcobalamin. J Am Geriatr Soc 2014;62(8):1611–2.][9. Huijts M., van Oostenbrugge R., Rouhl R.P. et al. Effects of vitamin B12 supplementation on cognition, depression, and fatigue in patients with lacunar stroke. Int Psychogeriatr 2013;25(3):508–10.Huijts M., van Oostenbrugge R., Rouhl R.P. et al. Effects of vitamin B12 supplementation on cognition, depression, and fatigue in patients with lacunar stroke. Int Psychogeriatr 2013;25(3):508–10.][10. Moore E., Mander A., Ames D. et al. Cognitive impairment and vitamin B12: a review. Int Psychogeriatr 2012;24(4):541–56.Moore E., Mander A., Ames D. et al. Cognitive impairment and vitamin B12: a review. Int Psychogeriatr 2012;24(4):541–56.][11. Obeid R., Jung J., Falk J. et al. Serum vitamin B12 not reflecting vitamin B12 status in patients with type 2 diabetes. Biochimie 2013;95(5):1056–61.Obeid R., Jung J., Falk J. et al. Serum vitamin B12 not reflecting vitamin B12 status in patients with type 2 diabetes. Biochimie 2013;95(5):1056–61.][12. Malouf R., Grimley Evans J. Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Cochrane Database Syst Rev 2008;(4):CD004514.Malouf R., Grimley Evans J. Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Cochrane Database Syst Rev 2008;(4):CD004514.][13. Reynolds E.H. Folic acid, ageing, depression, and dementia. BMJ 2002;324(7352):1512–5.Reynolds E.H. Folic acid, ageing, depression, and dementia. BMJ 2002;324(7352):1512–5.][14. Guidolin L., Vignoli A., Canger R. Worsening in seizure frequency and severity in relation to folic acid administration. Eur J Neurol 1998;5(3):301–3.Guidolin L., Vignoli A., Canger R. Worsening in seizure frequency and severity in relation to folic acid administration. Eur J Neurol 1998;5(3):301–3.][15. Agnew-Blais J.С., Wassertheil-Smoller S., Kang J.H. et al. Folate, vitamin B-6, and vitamin B-12 intake and mild cognitive impairment and probable dementia in the Women's Health Initiative Memory Study. J Acad Nutr Diet 2015;115(2):231–41.Agnew-Blais J.С., Wassertheil-Smoller S., Kang J.H. et al. Folate, vitamin B-6, and vitamin B-12 intake and mild cognitive impairment and probable dementia in the Women's Health Initiative Memory Study. J Acad Nutr Diet 2015;115(2):231–41.][16. Зорилова И.В., Суслина З.А., Иллариошкин С.Н., Кистенев Б.А. Наследственно обусловленная гипергомоцистеинемия в патогенезе ишемического инсульта у лиц молодого возраста. Неврологический журнал 2005;10(2):14–7. [Zorilova I.V., Suslina Z.A., Illarioshkin S.N., Kistenev B.A. Inherited hyperhomocysteinemia in the pathogenesis of ischemic strokes of young persons. Nevrologicheskiy zhurnal = Neurological Journal 2005;10(2):14–7. (In Russ.)].Зорилова И.В., Суслина З.А., Иллариошкин С.Н., Кистенев Б.А. Наследственно обусловленная гипергомоцистеинемия в патогенезе ишемического инсульта у лиц молодого возраста. Неврологический журнал 2005;10(2):14–7. [Zorilova I.V., Suslina Z.A., Illarioshkin S.N., Kistenev B.A. Inherited hyperhomocysteinemia in the pathogenesis of ischemic strokes of young persons. Nevrologicheskiy zhurnal = Neurological Journal 2005;10(2):14–7. (In Russ.)].][17. Литвиненко И.В., Одинак М.М., Сологуб О.С. и др. Гипергомоцистеинемия при болезни Паркинсона – новый вариант осложнений проводимой терапии или специфический биохимический маркер заболеваний? Анналы клинической и экспериментальной неврологии 2008;2(2):13–7. [Litvinenko I.V., Odinak M.M., Sologub O.S. et al. Hyperhomocysteinemia with Parkinson's disease: a new variant of complications of the therapy performed or a specific biochemical marker of the diseases? Annaly klinicheskoy i eksperimental'noy nevrologii = Annals of Clinical and Experimental Neurology 2008;2(2):13–7. (In Russ.)].Литвиненко И.В., Одинак М.М., Сологуб О.С. и др. Гипергомоцистеинемия при болезни Паркинсона – новый вариант осложнений проводимой терапии или специфический биохимический маркер заболеваний? Анналы клинической и экспериментальной неврологии 2008;2(2):13–7. [Litvinenko I.V., Odinak M.M., Sologub O.S. et al. Hyperhomocysteinemia with Parkinson's disease: a new variant of complications of the therapy performed or a specific biochemical marker of the diseases? Annaly klinicheskoy i eksperimental'noy nevrologii = Annals of Clinical and Experimental Neurology 2008;2(2):13–7. (In Russ.)].][18. Калашникова Л.А., Добрынина Л.А., Устюжанина М.К. Гипергомоцистеинемия и поражение головного мозга. Неврологический журнал 2004;9(3):48–54. [Kalashnikova L.A., Dobrynina L.A., Ustyuzhanina M.K. Hyperhomocysteinemia and brain lesions. Nevrologicheskiy zhurnal = Neurological Journal 2004;9(3):48–54. (In Russ.)].Калашникова Л.А., Добрынина Л.А., Устюжанина М.К. Гипергомоцистеинемия и поражение головного мозга. Неврологический журнал 2004;9(3):48–54. [Kalashnikova L.A., Dobrynina L.A., Ustyuzhanina M.K. Hyperhomocysteinemia and brain lesions. Nevrologicheskiy zhurnal = Neurological Journal 2004;9(3):48–54. (In Russ.)].][19. Garcia A., Zanibbi K. Homocysteine and cognitive function in elderly people. CMAJ 2004;171(8):897–904.Garcia A., Zanibbi K. Homocysteine and cognitive function in elderly people. CMAJ 2004;171(8):897–904.][20. Sen S., Reddy P.L., Grewal R.P. et al. Hyperhomocysteinemia is associated with aortic atheroma progression in stroke/TIA patients. Front Neurol 2010;1:131.Sen S., Reddy P.L., Grewal R.P. et al. Hyperhomocysteinemia is associated with aortic atheroma progression in stroke/TIA patients. Front Neurol 2010;1:131.][21. Toole J.F., Malinow M.R., Chambless L.E. et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the vitamin intervention for stroke prevention (VISP) randomized controlled trial. JAMA 2004;291(5):565–75.Toole J.F., Malinow M.R., Chambless L.E. et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the vitamin intervention for stroke prevention (VISP) randomized controlled trial. JAMA 2004;291(5):565–75.][22. Dusitanond P., Eikelboom J.W., Hankey G.J. et al. Homocysteine-lowering treatment with folic acid, cobalamin, and pyridoxine does not reduce blood markers of inflammation, endothelial dysfunction, or hypercoagulability in patients with previous transient ischemic attack or stroke: a randomized substudy of the VITATOPS trial. Stroke 2005;36(1):144–6.Dusitanond P., Eikelboom J.W., Hankey G.J. et al. Homocysteine-lowering treatment with folic acid, cobalamin, and pyridoxine does not reduce blood markers of inflammation, endothelial dysfunction, or hypercoagulability in patients with previous transient ischemic attack or stroke: a randomized substudy of the VITATOPS trial. Stroke 2005;36(1):144–6.][23. Hankey G.J., Ford A.H., Yi Q. et al. Effect of B vitamins and lowering homocysteine on cognitive impairment in patients with previous stroke or transient ischemic attack: a prespecified secondary analysis of a randomized, placebo-controlled trial and meta-analysis. Stroke 2013;44(8):2232–9.Hankey G.J., Ford A.H., Yi Q. et al. Effect of B vitamins and lowering homocysteine on cognitive impairment in patients with previous stroke or transient ischemic attack: a prespecified secondary analysis of a randomized, placebo-controlled trial and meta-analysis. Stroke 2013;44(8):2232–9.][24. Leblhuber F., Walli J., Artner-Dworzak E. et al. Hyperhomocysteinemia in dementia. J Neural Transm 2000;107(12):1469–74.Leblhuber F., Walli J., Artner-Dworzak E. et al. Hyperhomocysteinemia in dementia. J Neural Transm 2000;107(12):1469–74.][25. Seshadri S., Beiser A., Selhub J. et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 2002;346(7):476–83.Seshadri S., Beiser A., Selhub J. et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 2002;346(7):476–83.][26. Hogervorst E., Ribeiro H.M., Molyneux A. et al. Plasma homocysteine levels, cerebrovascular risk factors, and cerebral white matter changes (leukoaraiosis) in patients with Alzheimer disease. Arch Neurol 2002;59(5):787–93.Hogervorst E., Ribeiro H.M., Molyneux A. et al. Plasma homocysteine levels, cerebrovascular risk factors, and cerebral white matter changes (leukoaraiosis) in patients with Alzheimer disease. Arch Neurol 2002;59(5):787–93.][27. Prins N.D., den Heijer T., Hofman A. et al. Homocysteine and cognitive function in the elderly: The Rotterdam Scan Study. Neurology 2002;59(9):1375–80.Prins N.D., den Heijer T., Hofman A. et al. Homocysteine and cognitive function in the elderly: The Rotterdam Scan Study. Neurology 2002;59(9):1375–80.][28. Schafer J.H., Glass T.A., Bolla K.I. et al. Homocysteine and cognitive function in a population-based study of older adults. J Am Geriatr Soc 2005;53(3):381–8.Schafer J.H., Glass T.A., Bolla K.I. et al. Homocysteine and cognitive function in a population-based study of older adults. J Am Geriatr Soc 2005;53(3):381–8.][29. Loscalzo J. Homocysteine and dementias. N Engl J Med 2002;346(7):466–8.Loscalzo J. Homocysteine and dementias. N Engl J Med 2002;346(7):466–8.][30. Reis E.A., Zugno A.I., Franzon R. et al. Pretreatment with vitamins E and C prevent the impairment of memory caused by homocysteine administration in rats. Metab Brain Dis 2002;17(3):211–7.Reis E.A., Zugno A.I., Franzon R. et al. Pretreatment with vitamins E and C prevent the impairment of memory caused by homocysteine administration in rats. Metab Brain Dis 2002;17(3):211–7.][31. McMahon J.A., Green T.J., Skeaff C.M. et al. A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med 2006;354(26):2764–72.McMahon J.A., Green T.J., Skeaff C.M. et al. A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med 2006;354(26):2764–72.][32. Walker J.G., Batterham P.J., Mackinnon A.J. et al. Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community dwelling older adults with depressive symptoms – the Beyond Ageing Project: a randomized controlled trial. Am J Clin Nutr 2012;95(1):194–203.Walker J.G., Batterham P.J., Mackinnon A.J. et al. Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community dwelling older adults with depressive symptoms – the Beyond Ageing Project: a randomized controlled trial. Am J Clin Nutr 2012;95(1):194–203.][33. de Jager C.A., Oulhaj A., Jacoby R. et al. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int J Geriatr Psychiatry 2012;27(6):592–600.de Jager C.A., Oulhaj A., Jacoby R. et al. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int J Geriatr Psychiatry 2012;27(6):592–600.][34. Kwok T., Lee J., Law C.B. et al. A randomized placebo controlled trial of homocysteine lowering to reduce cognitive decline in older demented people. Clin Nutr 2011;30(3):297–302.Kwok T., Lee J., Law C.B. et al. A randomized placebo controlled trial of homocysteine lowering to reduce cognitive decline in older demented people. Clin Nutr 2011;30(3):297–302.][35. Douaud G., Refsum H., de Jager C.A. et al. Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. Proc Natl Acad Sci USA 2013;110(23): 9523–8.Douaud G., Refsum H., de Jager C.A. et al. Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. Proc Natl Acad Sci USA 2013;110(23): 9523–8.][36. Health Quality Ontario. Vitamin B12 and cognitive function: an evidence-based analysis. Ont Health Technol Assess Ser 2013;13(23):1–45.Health Quality Ontario. Vitamin B12 and cognitive function: an evidence-based analysis. Ont Health Technol Assess Ser 2013;13(23):1–45.]