r-n-jРоссийский неврологический журналRussian neurological journal2658-79472686-7192МИА10.30629/2658-7947-2019-24-5-54-60r-n-j-36Research ArticleЛЕКАРСТВЕННЫЕ ПРЕПАРАТЫ В НЕВРОЛОГИИDRUGS IN NEUROLOGYСравнительный анализ эффективности применения монотерапии донепезилом и комбинированной терапии донепезилом и акатинолом мемантином у больных с болезнью Альцгеймера на стадии легкой деменцииComparative analysis of the effectiveness of donepezil monotherapy and combination therapy with donepezil and akatinol memantine in patients with Alzheimer's disease at the stage of mild dementiahttps://orcid.org/0000-0002-4193-688XТкачеваО. Н.TkachevaO. N.

Москва, 129226. 

129226, 16, 1st Leonova street, Moscow.

https://orcid.org/0000-0001-5272-0454РунихинаН. К.RunikhinaN. K.

Москва, 129226. 

129226, 16, 1st Leonova street, Moscow.

https://orcid.org/0000-0003-2597-981XМхитарянЭ. А.MkhitaryanE. A.

Москва, 129226. 

129226, 16, 1st Leonova street, Moscow.

melen99@mail.ruhttps://orcid.org/0000-0002-3110-4764КоберскаяН. Н.KoberskayaN. N.

Москва, 129226; Москва, 119991.

129226, 16, 1st Leonova street, Moscow; Trubetskaya, 8/2, Moscow, 119991.

https://orcid.org/0000-0002-2196-1068МаневичТ. М.ManevichT. M.

Москва, 129226. 

129226, 16, 1st Leonova street, Moscow.

Российский национальный исследовательский медицинский университет имени Н.И. Пирогова Минздрава РоссииРоссияRussian Clinical and Research Center of Gerontology Pirogov Russian National Research Medical UniversityRussian FederationРоссийский национальный исследовательский медицинский университет имени Н.И. Пирогова Минздрава России; Кафедра нервных болезней и нейрохирургии ФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский Университет)РоссияRussian Clinical and Research Center of Gerontology Pirogov Russian National Research Medical University; The Chair of diseases of nervous system and neurosurgery. I.M. Sechenov First Moscow Medical State UniversityRussian Federation2019150120202455460Copyright © Ткачева О.Н., Рунихина Н.К., Мхитарян Э.А., Коберская Н.Н., Маневич Т.М., 20202020Ткачева О.Н., Рунихина Н.К., Мхитарян Э.А., Коберская Н.Н., Маневич Т.М.Tkacheva O.N., Runikhina N.K., Mkhitaryan E.A., Koberskaya N.N., Manevich T.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.r-n-j.com/jour/article/view/36

Стандартом терапии деменции при болезни Альцгеймера (БА) является применение базисных препаратов, воздействующих на холинергическую и глутаматергическую системы.

Целью  исследования  являлась  сравнительная  оценка  комбинированной  терапии  антагонистом  NMDA-рецепторов акатинолом мемантином и ингибитором ацетилхолинэстеразы донепезилом по сравнению с монотерапией донепезилом у больных с БА на стадии легкой деменции.

Материал и методы

Материал и методы. В исследование включено 35 пациентов с БА (средний возраст 78,51 ± 6,08 года) на стадии легкой деменции. 35% пациентов  получали монотерапию  донепезилом  (алзепил®),  65% пациентов получали комбинированную  терапию донепезилом  и акатинолом  мемантином.  Период наблюдения  составил 12 мес., в течение которого каждые 3 мес. пациентам проводилось нейропсихологическое обследование, которое включало краткую шкалу оценки психического статуса, батарею тестов на лобную дисфункцию, тест на память с оценкой непосредственного и отсроченного воспроизведения «12 слов», тест на называние литеральных и категориальных ассоциаций, тест рисования часов, тест последовательного соединения цифр часть А.

Результаты

Результаты. У пациентов, получавших комбинированную терапию, через 3 мес. лечения выявлялась положительная динамика практически по всем когнитивным шкалам, которая продолжала нарастать в течение всего периода наблюдения, в отличие от пациентов на монотерапии, у которых имелась лишь стабилизация когнитивного статуса.

Заключение

Заключение.  Назначение  комбинированной  терапии  акатинолом  мемантином  и донепезилом  пациентам с БА на стадии легкой деменции в течение 12 мес. более эффективно, чем монотерапия донепезилом.

The standard for the treatment of dementia in Alzheimer's disease (AD) is the use of basic medicines affecting the cholinergic and glutamatergic systems.

The aim of the study was a comparative evaluation of combined treatment with an NMDA receptor antagonist akatinol memantine and donepezil — acetylcholinesterase  inhibitor, compared with donepezil monotherapy in AD patients with mild dementia.

Material and methods

Material and methods. The study included 35 patients with AD (average age 78.51 years old ± 6.08) at the stage of mild dementia. 35% of patients received donepezil monotherapy (alzepil), 65% of patients received donepezil and akatinol memantine combined treatment. The observation period was 12 months. During this period, the patients underwent a neuropsychological examination every 3 months. It included a Mini Mental State Examination, Frontal assessment battery, memory test with an assessment of immediate and delayed reproduction of «12 words», verbal fluency (phonetic and semantic), clock drawing test, Trial making test, part A.

Results

Results. In patients, who received the combined treatment, improvement was detected on almost all cognitive scales, in 3 months of the therapy. It continued to increase throughout the whole observation period. And, contrary-wise, in patients, who received monotherapy, only stabilization of cognitive status was manifested.

Conclusion

Conclusion. The administration of combined treatment with akatinol memantine and donepezil to patients with AD at the stage of mild dementia during the period of 12 months, is more effective than donepezil monotherapy.

болезнь Альцгеймерамонотерапиякомбинированная терапиядонепезилмемантинAlzheimer's diseasemonotherapycombined treatmentdonepezilakatinol memantineReferencesЯхно Н.Н., Захаров В.В., Локшина А.Б. и др. Деменции: практическое руководство для врачей. М. : МЕДпресс-информ, 2011, 272 с.Yаkhno N.N., Zaharov V.V., Lokshina A.B. et al. Dementia: A Practical Guide for Physicians.. M. : MEDpress-inform, 2011, 272 p. (In Russian).Левин О.С. Диагностика и лечение когнитивных нарушений и деменции в клинической практике. М. : МЕДпресс, 2019, 448 с.Levin O.S. Diagnosis and treatment of cognitive impairment and dementia in clinical practice.. M. : MEDpress, 2019, 448 p. (In Russian).Емелин А.Ю., Лобзин В.Ю., Воробьёв С.В. Когнитивные нарушения: руководство для врачей, М., 2019, 416 с.Emelin A.Yu., Lobzin V.Yu., Vorob'yov S.V. Cognitive Impairment: A Guide for Physicians. Moscow, 2019, 416 p. (In Russian).Захаров В.В. Когнитивная неврология. М.: Медфорум — Альфа, 2019, 188 с.Zaharov V.V. Cognitive neurology. M.: Medforum — Al'fa, 2019, 188 p. (In Russian).Гаврилова С.И. Болезнь Альцгеймера. Современные представления о диагностике и терапии. М., 2018, 136 с.Gavrilova S.I. Alzheimer's disease. Modern ideas about diagnosis and therapy. М., 2018, 136 p. (In Russian).Kishi T., Matsunaga S., Oya K. et al. Memantine for Alzheimer's Disease: An Updated Systematic Review and Meta-analysis. J. Alzheimers Dis. 2017;60(2):401–425. doi:10.3233/JAD-170424.Kishi T., Matsunaga S., Oya K. et al. Memantine for Alzheimer's Disease: An Updated Systematic Review and Meta-analysis. J. Alzheimers Dis. 2017;60(2):401–425. doi:10.3233/JAD-170424.McShane R., Westby M.J., Roberts E. et al. Memantine for dementia. Cochrane Database Syst Rev., 2019;Mar 20;3:CD003154. doi:10.1002/14651858.CD003154.pub6.McShane R., Westby M.J., Roberts E. et al. Memantine for dementia. Cochrane Database Syst Rev., 2019;Mar 20;3:CD003154. doi:10.1002/14651858.CD003154.pub6.Schmidt R., Hofer E., Bouwman F.H. 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;22:889–898.Schmidt R., Hofer E., Bouwman F.H. 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;22:889–898.Яхно Н.Н., Преображенская И.С., Захаров В.В., Мхитарян Э.А. Эффективность акатинола мемантина у пацентов с недементными когнитивными расстройствами. Результаты многоцентрового клинического наблюдения. Неврологический журнал. 2010;15(2):52–58.Yakhno N.N., Preobrazhenskaya I.S., Zaharov V.V., Mhitaryan E.A. Efficacy of akatinol memantine in patients with non-cognitive cognitive impairment. Results of a multicenter clinical observation. Nevrologicheskij zhurnal. 2010;15(2): 52–58. (In Russian).Захаров В.В., Вознесенская Т.Г. Нервно-психические нарушения: диагностические тесты. М.: МЕДпресс-информ, 2013; 320 с.Zaharov V.V., Voznesenskaya T.G. Neuropsychiatric Disorders: Diagnostic Tests. M.: MEDpress-inform, 2013; 320 p. (In Russian).Chen R., Chan P.T., Chu H., et al. Treatment effects between monotherapy of donepezil versus combination with memantine for Alzheimer disease: A meta-analysis. PLoS One. 2017;12(8):e0183586. Published 2017 Aug 21. doi:10.1371/journal.pone.0183586.Chen R., Chan P.T., Chu H., et al. Treatment effects between monotherapy of donepezil versus combination with memantine for Alzheimer disease: A meta-analysis. PLoS One. 2017;12(8):e0183586. Published 2017 Aug 21. doi:10.1371/journal.pone.0183586.Kennedy R.E., Cutter G.R., Fowler M.E., Schneider L.S. Association of Concomitant Use of Cholinesterase Inhibitors or Memantine With Cognitive Decline in Alzheimer Clinical Trials: A Meta-analysis. JAMA Netw Open. 2018;1(7):e184080. Published 2018 Nov 2. doi:10.1001/jamanetworkopen.2018.4080.Kennedy R.E., Cutter G.R., Fowler M.E., Schneider L.S. Association of Concomitant Use of Cholinesterase Inhibitors or Memantine With Cognitive Decline in Alzheimer Clinical Trials: A Meta-analysis. JAMA Netw Open. 2018;1(7):e184080. Published 2018 Nov 2. doi:10.1001/jamanetworkopen.2018.4080.Folch J., Busquets O., Ettcheto M., et al. Memantine for the Treatment of Dementia: A Review on its Current and Future Applications. J Alzheimers Dis. 2018;62(3):1223–1240. doi:10.3233/JAD-170672.Folch J., Busquets O., Ettcheto M., et al. Memantine for the Treatment of Dementia: A Review on its Current and Future Applications. J Alzheimers Dis. 2018;62(3):1223–1240. doi:10.3233/JAD-170672.Lopez O.L., Becker J.T., Wahed A.S., et al. Long-term effects of the concomitant use of memantine with cholinesterase inhibition in Alzheimer disease [published correction appears in J. Neurol Neurosurg Psychiatry. 2009 Sep 1;80(9):1056]. J. Neurol Neurosurg Psychiatry. 2009;80(6):600–607. doi:10.1136/jnnp.2008.158964.Lopez O.L., Becker J.T., Wahed A.S., et al. Long-term effects of the concomitant use of memantine with cholinesterase inhibition in Alzheimer disease [published correction appears in J. Neurol Neurosurg Psychiatry. 2009 Sep 1;80(9):1056]. J. Neurol Neurosurg Psychiatry. 2009;80(6):600–607. doi:10.1136/jnnp.2008.158964.Parsons C.G., Danysz W., Dekundy A., Pulte I. Memantine and Cholinesterase Inhibitors: Complementary Mechanisms in the Treatment of Alzheimer’s Diseas. Neurotox Res. 2013;24(3): 358–36. Published online 2013 May 9. doi:10.1007/s12640-013-9398-z.Parsons C.G., Danysz W., Dekundy A., Pulte I. Memantine and Cholinesterase Inhibitors: Complementary Mechanisms in the Treatment of Alzheimer’s Diseas. Neurotox Res. 2013;24(3): 358–36. Published online 2013 May 9. doi:10.1007/s12640-013-9398-z.Fournier G.N., Materi L.M., Semba K., Rasmusson D.D. Cortical acetylcholine release and electroencephalogram activation evoked by ionotropic glutamate receptor agonists in the rat basal forebrain. Neuroscience. 2004;123:785–792.Fournier G.N., Materi L.M., Semba K., Rasmusson D.D. Cortical acetylcholine release and electroencephalogram activation evoked by ionotropic glutamate receptor agonists in the rat basal forebrain. Neuroscience. 2004;123:785–792.Wu M., Hajszan T., Xu C., Leranth C., Alreja M. Group I metabotropic glutamate receptor activation produces a direct excitation of identified septohippocampal cholinergic neurons. J Neurophysiol. 2004;92:1216–1225.Wu M., Hajszan T., Xu C., Leranth C., Alreja M. Group I metabotropic glutamate receptor activation produces a direct excitation of identified septohippocampal cholinergic neurons. J Neurophysiol. 2004;92:1216–1225.Fadel J., Sarter M., Bruno J.P. Basal forebrain glutamatergic modulation of cortical acetylcholine release. Synapse. 2001;39:201–212.Fadel J., Sarter M., Bruno J.P. Basal forebrain glutamatergic modulation of cortical acetylcholine release. Synapse. 2001;39:201–212.Moor E., Auth F., DeBoer P., Westerink B.H.C. Septal and hippocampal glutamate receptors modulate the output of acetyl-choline in hippocampus: a microdialysis study. J. Neurochem. 1996;67:310–316.Moor E., Auth F., DeBoer P., Westerink B.H.C. Septal and hippocampal glutamate receptors modulate the output of acetyl-choline in hippocampus: a microdialysis study. J. Neurochem. 1996;67:310–316.Allen T.G., Abogadie F.C., Brown D.A. Simultaneous release of glutamate and acetylcholine from single magnocellular “cholinergic” basal forebrain neurons. J. Neurosci. 2006;26:1588–1595.Allen T.G., Abogadie F.C., Brown D.A. Simultaneous release of glutamate and acetylcholine from single magnocellular “cholinergic” basal forebrain neurons. J. Neurosci. 2006;26:1588–1595.Enz A., Gentsch C. Co-administration of memantine has no effect on the in vitro or ex vivo determined acetylcholinesterase inhibition of rivastigmine in the rat brain. Neuropharmacology. 2004;47:408–413.Enz A., Gentsch C. Co-administration of memantine has no effect on the in vitro or ex vivo determined acetylcholinesterase inhibition of rivastigmine in the rat brain. Neuropharmacology. 2004;47:408–413.Wenk G.L., Quack G., Moebius H.J., Danysz W. No interaction of memantine with acetylcholinesterase inhibitors approved for clinical use. Life Sci. 2000;66:1079–1083.Wenk G.L., Quack G., Moebius H.J., Danysz W. No interaction of memantine with acetylcholinesterase inhibitors approved for clinical use. Life Sci. 2000;66:1079–1083.Patel L., Grossberg G.T. Combination therapy for Alzheimer’s disease. Drugs Aging. 2011;28:539–546.Patel L., Grossberg G.T. Combination therapy for Alzheimer’s disease. Drugs Aging. 2011;28:539–546.Schmidtke K., Holthoff V., Kressig R.W., Molinuevo J.L. Combination of Memantine and cholinesterase inhibitors in the treatment of AD. Neurology News. 2011;1:1–8.Schmidtke K., Holthoff V., Kressig R.W., Molinuevo J.L. Combination of Memantine and cholinesterase inhibitors in the treatment of AD. Neurology News. 2011;1:1–8.Gillette-Guyonnet S., Andrieu S., Nourhashemi F., Gardette V., Coley N., Cantet C., et al. Long-term progression of Alzheimer’s disease in patients under antidementia drugs. Alzheimers Dement. 2011;7:579–592.Gillette-Guyonnet S., Andrieu S., Nourhashemi F., Gardette V., Coley N., Cantet C., et al. Long-term progression of Alzheimer’s disease in patients under antidementia drugs. Alzheimers Dement. 2011;7:579–592.Howard R., McShane R., Lindesay J., Ritchie C., Baldwin A., Barber R., et al. Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N. Engl. J. Med. 2012;366:893–903.Howard R., McShane R., Lindesay J., Ritchie C., Baldwin A., Barber R., et al. Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N. Engl. J. Med. 2012;366:893–903.Lachaine J., Beauchemin C., Legault M., Bineau S. Economic evaluation of the impact of memantine on time to nursing home admission in the treatment of Alzheimer disease. Can. J. Psychiatry. 2011;56:596–604.Lachaine J., Beauchemin C., Legault M., Bineau S. Economic evaluation of the impact of memantine on time to nursing home admission in the treatment of Alzheimer disease. Can. J. Psychiatry. 2011;56:596–604.

The authors declare that there are no conflicts of interest present.