Neurology, Neuropsychiatry, Psychosomatics

Advanced search

Alzheimer's disease

Full Text:


Despite progress made in laboratory methods, genetic studies, and modern neuroimaging, the diagnosis of diseases that cause dementia makes difficulties. The review presents an update on the epidemiology, risk factors, pathogenesis, clinical presentation, diagnosis, and treatment of Alzheimer's disease (AD). It discusses the issues of symptomatic and pathogenetic treatments and combination therapy for AD. The efficacy of memantine (akatinol memantine) and the expediency of its use at different stages of the disease in patients with AD are noted. Non-pharmacological treatments for this disease, including physical activity and cognitive training, are considered.

About the Author

N. N. Koberskaya
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia
Russian Federation

Department of Nervous System Diseases and Neurosurgery, Faculty of General Medicine, 

11, Rossolimo St., Build. 1, Moscow 119021


1. Prince M, Wimo A, Guerchet M, et al. An analysis of prevalence, incidence, cost & trends. In: Alzheimer's Disease International. World Alzheimer Report 2015. The global impact of dementia. London; 2015.

2. Parfenov VA, Kabaeva AR. Maintaining Alzheimer's patients. Medsovet. 2018;(1):6-11 (In Russ.).

3. Belousov YuB, Zyryanov SK, Belousov DYu, Beketov AS. Clinical and economic aspects of Alzheimer's disease therapy in Russia. Kachestvennaya Klinicheskaya Praktika. 2009;(1):3-28 (In Russ.).

4. Parfenov VA, Zakharov VV, Preobrazhenskaya IS. Kognitivnye rasstroistva [Cognitive disorders]. Moscow: Remedium; 2014 (In Russ.).

5. Hurd MD, Martorell P, Delavande A, et al. Monetary costs of dementia in the United States. New Engl J Med. 2013;368(14):1326-34. doi: 10.1056/NEJMsa1204629

6. Mielke MM, Vemuri P, Rocca WA. Clinical epidemiology of Alzheimer's disease: assessing sex and gender differences. Clin Epidemiol. 2014;6:37-48. doi: 10.2147/CLEP.S37929

7. Murray ME, Graff-Radford NR, Ross OA, et al. Neuropathologically defined subtypes of Alzheimer's disease with distinct clinical characteristics: a retrospective study. Lancet Neurol. 2011;10:785-96. doi: 10.1016/S1474-4422 (11)70156-9

8. Liesinger AM, Graff-Radford NR, Duara R, et al. Sex and age interact to determine clinicopathologic differences in Alzheimer's disease. Acta Neuropathol. 2018;136:873-85. doi: 10.1007/s00401-018-1908-x

9. Launer LJ, Andersen K, Dewey ME, et al. Rates and risk factors for dementia and Alzheimer's disease: results from EURODEM pooled analyses. EURODEM incidence research group and work groups. European studies of Dementia. Neurology. 1999;52:78-84. doi: 10.1212/WNL.52.1.78

10. Chene G, Beiser A, Au R, et al. Gender and incidence of dementia in the Framingham heart study from mid-adult life. Alzheimer's Dement. 2015;11:310-20. doi: 10.1016/j.jalz.2013.10.005

11. Ngandu T, Lehtisalo J, Solomon A, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015;385: 2255-63. doi: 10.1016/S0140-6736(15)60461-5

12. Gauthier S, Zhang H, Ng KP, et al. Impact of the biological definition of Alzheimer's disease using amyloid, tau and neurodegeneration (ATN): what about the role of vascular changes, inflammation, Lewy body pathology. Translat Neurodegenerat. 2018;7:12. doi: 10.1186/s40035-018-0117-9

13. Xu W, Tan L, Wang HF, et al. Education and Risk of Dementia: Dose-Response MetaAnalysis of Prospective Cohort Studies. Mol Neurobiol. 2016 Jul;53(5):3113-23. doi: 10.1007/s12035-015-9211-5. Epub 2015 May 17.

14. Meng X, D'Arcy C. Education and dementia in the context of the cognitive reserve hypothesis: a systematic review with meta-analyses and qualitative analyses. PLoS One. 2012;7:38268. doi: 10.1371/journal.pone.0038268

15. Mehta KM, Stewart AL, Langa KM, et al. «Below average» self-assessed school performance and Alzheimer's disease in the Aging, Demographics, and Memory Study. Alzheimers Dement. 2009;5:380-7. doi: 10.1016/j.jalz.2009.07.039

16. Snowdon DA, Greiner LH, Markesbery WR. Linguistic ability in early life, the neuropathology of Alzheimer's disease, cerebrovascular disease Findings from the Nun Study. Ann N Y Acad Sci. 2000;903:34-8. doi: 10.1111/j.1749-6632.2000.tb06347.x

17. Snowdon DA, Kemper SJ, Mortimer JA, et al. Linguistic ability in early life, cognitive function Alzheimer's disease in late life Findings from the Nun Study. JAMA. 1996; 275:528-32. doi: 10.1001/jama.1996.03530310034029

18. De Luca V, Orfei MD, Gaudenzi S, et al. Inverse effect of the APOE epsilon4 allele in late- and early-onset Alzheimer's disease. Eur Arch Psychiatry Clin Neurosci. 2016 Oct;266(7): 599-606. doi: 10.1007/s00406-015-0663-4. Epub 2015 Dec 29.

19. Dean DC 3rd, Jerskey BA, Chen K, et al. Brain Differences in Infants at Differential Genetic Risk for Late-Onset Alzheimer Disease: A Cross-sectional Imaging Study. JAMA Neurol. 2014;71(1):11-22. doi: 10.1001/jamaneurol.2013.4544

20. Shaw P, Lerch JP, Pruessner JC, et al. Cortical morphology in children and adolescents with different apolipoprotein E gene polymorphisms: an observational study. Lancet Neurol. 2007;6:494-500. doi: 10.1016/S1474-4422(07)70106-0

21. Valla J, Yaari R, Wolf AB, et al. Reduced posterior cingulate mitochondrial activity in expired young adult carriers of the APOE epsilon4 allele, the major late-onset Alzheimer's susceptibility gene. J Alzheimers Dis. 2010;22: 307-13. doi: 10.3233/JAD-2010-100129

22. Bloss CS, Delis DC, Salmon DP, Bondi MW. Decreased cognition in children with risk factors for Alzheimer's disease. Biol Psychiatry. 2008;64:904-6. doi: 10.1016/j.biopsych.2008.07.004

23. Chartier-Harlin MC, Parfitt M, Legrain S, et al. Apolipoprotein E, epsilon 4 allele as a major risk factor for sporadic early and lateonset forms of Alzheimer's disease: analysis of the 19q13.2 chromosomal region. Hum Mol Genet. 1994;3:569-74. doi: 10.1093/hmg/3.4.569

24. Nicolas G, Charbonnier C, Wallon D, et al. SORL1 rare variants: a major risk factor for familial early-onset Alzheimer's disease. Molecular Psychiatry. 2016;21(6):831-6. doi: 10.1038/mp.2015.121

25. Bralten J, Arias-Vasquez A, Makkinje R, et al. Association of the Alzheimer's gene SORL1 with hippocampal volume in young, healthy adults. Am J Psychiatry. 2011;168: 1083-9. doi: 10.1176/appi.ajp.2011.10101509

26. Vos SJ, Xiong C, Visser PJ, et al. Preclinical Alzheimer's disease and its outcome: a longitudinal cohort study. Lancet Neurol. 2013;12: 957-65. doi: 10.1016/S1474-4422(13)70194-7

27. Gomez-Isla T, Hollister R, West H, et al. Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease. Ann Neurol. 1997;41:17-24. doi: 10.1002/ana.410410106

28. Chertkow H, Feldman HH, Jcova C, et al. Definitions of dementia and predementia states in Alzheimer's disease and vascular cognitive impairment: consensus from the Canadian conference on diagnosis of dementia. Alzheimers Res Ther. 2013;5(Suppl 1).

29. Yakhno NN, Koberskaya NN, Zakharov VV, et al. The effect of age, comorbid cardiovascular and emotional factors on a mild cognitive decline in middle, old and old age. Nevrologicheskii Zhurnal. 2018;23(6):309-15 (In Russ.).

30. Dubois B, Hampel H, Feldman HH, et al. Proceedings of the Meeting of the International Working Group (IWG) and the American Alzheimer's Association on «The Preclinical State of AD»; July 23, 2015; Washington DC, USA. Alzheimers Dement. 2016;12:292-323. doi: 10.1016/j.jalz.2016.02.002

31. Sperling R, Mormino E, Johnson K. The evolution of preclinical Alzheimer's disease: implications for prevention trials. Neuron. 2014; 84:608-22. doi: 10.1016/j.neuron.2014.10.038

32. Mattsson N, Andreasson U, Persson S, et al. The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers. Alzheimers Dement. 2011;7:386-95. doi: 10.1016/j.jalz.2011.05.2243

33. Dubois B, Feldman HH, Jacova C, et al. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDSADRDA criteria. Lancet Neurol. 2007;6:734-46. doi: 10.1016/S1474-4422(07)70178-3

34. Mapstone M, Cheema AK, Fiandaca MS, et al. (2014) Plasma phospholipids identify antecedent memory impairment in older adults. Nat Med. 2014;20:415-8. doi: 10.1038/nm.3466

35. Yerbury JJ, Poon S, Meehan S, et al. The extracellular chaperone clusterin influences amyloid formation and toxicity by interacting with prefibrillar structures. FASEB J. 2007;21: 2312-22. doi: 10.1096/fj.06-7986com

36. Schrijvers EMC, Koudstaal PJ, Hofman A, Breteler MMB. Plasma clusterin and the risk of Alzheimer disease. JAMA. 2011;305:1322-6. doi: 10.1001/jama.2011.381

37. Jack Jr CR, Knopman DS, Jagust WJ, et al. Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013;12:207-16. doi: 10.1016/S1474-4422(12)70291-0

38. Ossenkoppele R, Schonhaut DR, Schö ll M, et al. Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease. Brain. 2016;139:1551-67. doi: 10.1093/brain/aww027

39. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging and the Alzheimer's Association workgroup. Synergistic effect of β-amyloid and neurodegeneration on cognitive decline in clinically normal individuals. JAMA Neurol. 2014;71:1379-85. doi: 10.1001/jamaneurol.2014.2031

40. Onyike CU, Chaney G-AS. Alzheimer Disease at the Extremes of Age: Clinical Epidemiology, Diagnosis and Care. Alzheimer's Association International Conference, AAIC. London; 2017.

41. Giacobini E. Cholinesterases in human brain: the effect of cholinesterase inhibitors on Alzheimer's disease and related disorders. In: Giacobini E, Pepeu G, editors. The Brain Cholinergic System in Health and Disease. Oxon, UK: Informa Healthcare; 2006. P. 235-64.

42. Pharmaceutical Research and Manufacturers of America. Researching Alzheimer's Medicines: Setbacks and Stepping Stones. 2012.

43. Hardy J, Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends Pharmacol Sci. 1991;12:383-8. doi: 10.1016/0165-6147(91)90609-V

44. Hung SY, Fu WM. Drug candidates in clinical trials for Alzheimer's disease. J Biomed Sci. 2017;24:47. doi: 10.1186/s12929-017-0355-7

45. Adolfsson O, Pihlgren M, Toni N, et al. An effector-reduced anti-β-Amyloid (Aβ) antibody with unique Aβ binding properties promotes neuroprotection and glial engulfment of Aβ. J Neurosci. 2012;32:9677-89. doi: 10.1523/JNEUROSCI.4742-11.2012

46. Doody RS, Thomas RG, Farlow M, et al. (2014) Phase 3 trials of solanezumab for mildto-moderate Alzheimer's disease. N Engl J Med. 2014;370:311-21. doi: 10.1056/NEJMoa1312889

47. Sevigny J, Chiao P, Bussiere T, et al. (2016) The antibody aducanumab reduces A plaques in Alzheimer's disease. Nature. 2016;537:50-6. doi: 10.1038/nature19323

48. Liang J, Li J, Jia R. Identification of the optimal cognitive drugs among Alzheimer's disease: a Bayesian meta-analytic review. Clin Intervent Aging. 2018;13:2061-73. doi: 10.2147/CIA.S184968

49. Cummings J, Aisen PS, DuBois B, et al. Drug development in Alzheimer's disease: The path to 2025. Alzheimer's Res Ther. 2016 Sep 20;8(1):39. doi: 10.1186/s13195-016-0207-9

50. Schmidt R, Ropele S, Ebenbauer B, et al. Memantine effects on brain volume, glucose metabolism and cognition in AD patients. Eur J Neurol. 2007;14(1):2526.

51. Inoue Y, Ueda M, Masuda T, et al. Memantine attenuates vascular amyloid β deposits and spontaneous hemorrhages in mouse models of cerebral amyloid angiopathy. Alzheimer's Association International Conference, AAIC. London; 2017.

52. Walker V, Davies N, Kehoe P, et al. What isthe impact of regulatory guidance and expiry ofdrug patents on dementia drug prescriptions in England? A trend analysis in the Clinical Practice Research Datalink. Alzheimers Res Ther. 2018 May 29;10(1):51. doi: 10.1186/s13195-018-0379-6

53. Erickson KI, Raji CA, Lopez OL, et al. Physical activity predicts gray matter volume in late adulthood: The Cardiovascular Health Study. Neurology. 2010;75:1415-22. doi: 10.1212/WNL.0b013e3181f88359

54. Nagamatsu LS, Handy TC, Hsu CL, et al. Resistance training promotes cognitive and functional brain plasticity in seniors with probable mild cognitive impairment: A 6-month randomized controlled trial. Arch Intern Med. 2013;172:666-8. doi: 10.1001/archinternmed.2012.379

55. Laxton AW, Tang-Wai DF, McAndrews MP, et al. A phase I trial of deep brain stimulation of memory circuits in Alzheimer's disease. Ann Neurol. 2010;68:521-34. doi: 10.1002/ana.22089

56. Leinenga G, Gö tz J. Scanning ultrasound removes amyloid- and restores memory in an Alzheimer's disease mouse model. Sci Transl Med. 2015;7:278ra33. doi: 10.1126/scitranslmed.aaa2512

57. Koberskaya NN. Current views of the risk factors, diagnosis, and therapy of Alzheimer's disease (according to the proceedings of the Alzheimer's Association International Conference, London, 2017). Nevrologiya, Neiropsikhiatriya, Psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2017;9(3):81-7 (In Russ.). doi: 10.14412/2074-2711-2017-3-81-87

58. Koberskaya NN. Early diagnosis of Alzheimer's disease. Effektivnaya farmakoterapiya. Nevrologiya. 2017;3(31):20-7 (In Russ.).


For citations:

Koberskaya N.N. Alzheimer's disease. Neurology, Neuropsychiatry, Psychosomatics. 2019;11(3S):52-60. (In Russ.)

Views: 819

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

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