Management of patients with cognitive impairment

The management of patients with cognitive impairment (CI) is one of the urgent problems of modern medicine. Issues of diagnostics and therapy of patients with CI and their high mortality during the period of coronavirus infection are discussed. A wide prevalence of patients with mild CI (MCI), an important role of neuropsychological research in establishing CI, and frequent diagnosis of CI only at the stage of dementia were noted. In our country, CI is poorly diagnosed, the most common cause of CI in the elderly – Alzheimer's disease (AD) – is rarely established, patients are observed for a long time with a diagnosis of cerebrovascular disease (CVD). Some non-drug and drug methods can reduce the manifestations of CI, improve the quality of life of both the patients themselves and those around them. In severe CI, socio-psychological methods, stimulating patients to feasible household and social, physical and mental activity, and avoiding prolonged hospitalization are of primary importance. In addition to lifestyle changes, much attention in CI is given to the prevention of stroke, the treatment of arterial hypertension and diabetes mellitus. At the stage of dementia, cholinomimetic drugs (acetylcholinesterase inhibitors, donepezil, rivastigmine, galantamine) and the glutamate receptor blocker memantine are used. The use of choline alfoscerate in CI and the results of the multicenter, placebo-controlled ASCOMALVA study are discussed, in which, in patients with AD and CVD, the addition of choline alfoscerate to donepezil reduced the severity of CI, manifestations of depression, anxiety, and apathy. A new oral form of choline alfoscerate (Cerpechol) is reported that may improve patient compliance and be used in patients with swallowing disorders.

1. World Health Organization. Risk reduction of cognitive decline and dementia: WHO guidelines. Geneva: World Health Organization; 2019.

2. Orgeta V, Mukadam N, Sommerlad A, Livingston G. The Lancet Commission on dementia prevention, intervention, and care: a call for action. Ir J Psychol Med. 2019 Jun;36(2):85-8. doi:10.1017/ipm.2018.4

3. GBD 2016 Dementia Collaborators Global, regional, and national burden of Alzheimer's disease and other dementias, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019 Jan;18(1):88-106. doi:10.1016/S1474-4422(18)30403

4. Yakhno NN, Zakharov VV, Lokshina AB, et al. Dementsii. Rukovodstvo dlya vrachey [Dementia. Guide for doctors]. 3rd ed. Moscow: MEDpressinform; 2011 (In Russ.).

5. Parfenov VA, Zaharov VV, Preobrazhenskaja IS. Kognitivnyye rasstroystva [Cognitive disorders]. Moscow: Remedium; 2014 (In Russ.).

6. Parfenov VA. Distsirkulyatornaya entsefalopatiya i sosudistyye kognitivnyye rasstroystva [Dyscirculatory encephalopathy and vascular cognitive disorders]. Moscow: IMA-PRESS; 2017 (In Russ.).

7. Parfenov VA, Koberskaya NN. Bolezn' Al'tsgeymera [Alzheimer's disease]. Moscow: IMA-PRESS; 2022 (In Russ.).

8. Foley NC, Affoo RH, Martin RE. A systematic review and meta-analysis examining pneumonia-associated mortality in dementia. Dement Geriatr Cogn Disord. 2015;39(1-2):52-67. doi:10.1159/000367783. Epub 2014 Oct 22.

9. U.S. Department of Health and Human Services. Centers for Disease Control and Prevention. National Center for Health Statistics. CDC WONDER online database: About Provisional Mortality Statistics, 2018 Through Last Month. Available from: https://wonder.cdc.gov/mcd-icd10-provisional.html (accessed 07.02.2022).

10. Bianchetti A, Rozzini R, Guerini F, et al. Clinical Presentation of COVID19 in Dementia Patients. J Nutr Health Aging. 2020;24(6):560-2. doi:10.1007/s12603-020-1389-1

11. Morandi A, Di Santo SG, Zambon A, et al. Italian Study Group on Delirium (ISGoD). Delirium, Dementia, and In-Hospital Mortality: The Results From the Italian Delirium Day 2016, A National Multicenter Study. J Gerontol A Biol Sci Med Sci. 2019 May 16;74(6):910-6. doi:10.1093/gerona/gly154

12. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189-98. doi:10.1016/0022-3956(75)90026-6

13. Karimi L, Mahboub-Ahari A, Jahangiry L, et al. A systematic review and meta-analysis of studies on screening for mild cognitive impairment in primary healthcare. BMC Psychiatry. 2022;22:97. doi:10.1186/s12888-022-03730-8

14. Woods B, Arosio F, Diaz A, et al. Timely diagnosis of dementia? Family carers' experiences in 5 European countries. Int J Geriatr Psychiatry. 2019 Jan;34(1):114-21. doi:10.1002/gps.4997. Epub 2018 Oct 9.

15. Petersen RC. How early can we diagnose Alzheimer disease (and is it sufficient)? The 2017 Wartenberg lecture. Neurology. 2018 Aug 28;91(9):395-402. doi:10.1212/WNL.0000000000006088. Epub 2018 Aug 8.

16. Jack CR, Bennett DA, Blennow K, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018 Apr;14(4):535-62. doi:10.1016/j.jalz.2018.02.018

17. Dubois B, Villain N, Frisoni GB, et al. Clinical diagnosis of Alzheimer's disease: recommendations of the International Working Group. Lancet Neurol. 2021 Jun;20(6):484-96. doi:10.1016/S1474-4422(21)00066-1. Epub 2021 Apr 29.

18. Perini G, Cotta Ramusino M, Sinforiani E, et al. Cognitive impairment in depression: recent advances and novel treatments. Neuropsychiatr Dis Treat. 2019 May 10;15:1249-58. doi:10.2147/NDT.S199746. eCollection 2019.

19. Heser K, Bleckwenn M, Wiese B, et al. Age CoDe Study Group. Late-Life Depressive Symptoms and Lifetime History of Major Depression: Cognitive Deficits are Largely Due to Incipient Dementia rather than Depression. J Alzheimers Dis. 2016 Aug 1;54(1):185-99. doi:10.3233/JAD-160209

20. Connors MH, Quinto L, Brodaty H. Longitudinal outcomes of patients with pseudodementia: a systematic review. Psychol Med. 2019;49:727-37. doi:10.1017/S0033291718002829. Epub 2018 Oct 15.

21. Van Dyck CH, Swanson CJ, Aisen P. Lecanemab in Early Alzheimer's Disease. N Engl J Med. 2023;388:9-21. doi:10.1056/NEJMoa2212948

22. Tampi RR, Forester BP, Agronin M. Aducanumab: evidence from clinical trial data and controversies. Drugs Context. 2021 Oct 4;10:2021-7-3. doi:10.7573/dic.2021-7-3

23. Chalfont G, Milligan C, Simpson J. A mixed methods systematic review of multimodal non-pharmacological interventions to improve cognition for people with dementia. Dementia (London). 2020 May;19(4):1086-130. doi:10.1177/1471301218795289. Epub 2018 Sep 7.

24. Chalghaf N, Binarelli G. Effectiveness of Computerized Cognitive Training in Delaying Cognitive Function Decline in People With Mild Cognitive Impairment: Systematic Review and Meta-analysis. J Med Internet Res. 2022 Oct 27;24(10):e38624. doi:10.2196/38624

25. Komulainen P, Tuomilehto J, Savonen K, et al. Exercise, diet, and cognition in a 4-year randomized controlled trial: Dose-Responses to Exercise Training (DR's EXTRA). Am J Clin Nutr. 2021 Jun 1;113(6):1428-39. doi:10.1093/ajcn/nqab018

26. Van den Brink AC, Brouwer-Brolsma EM, Berendsen AAM, van de Rest O. The Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) Diets Are Associated with Less Cognitive Decline and a Lower Risk of Alzheimer's Disease – A Review. Adv Nutr. 2019 Nov 1;10(6):1040-65. doi:10.1093/advances/nmz054

27. Cocchiara RA, De Lucia F, Koci L, et al. Management of the early stage of Alzheimer's disease: a systematic review of literature over the past 10 years. Clin Ter. 2020 JulAug;171(4):e357-e368. doi:10.7417/CT.2020.2239

28. Chen R, Chan PT, Chu H, et al. Treatment effects between monotherapy of donepezil versus combination with memantine for Alzheimer disease: a metaanalysis. PloS One. 2017 Aug 21;12(8):e0183586. doi:10.1371/journal.pone.0183586. eCollection 2017.

29. 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 Jun 6;385(9984):2255-63. doi:10.1016/S0140-6736(15)60461-5. Epub 2015 Mar 12.

30. Barbagallo SG, Barbagallo M, Giordano M, et al. alpha-Glycerophosphocholine in the mental recovery of cerebral ischemic attacks. An Italian multicenter clinical trial. Ann N Y Acad Sci. 1994 Jun 30;717:253-69. doi:10.1111/j.1749-6632.1994.tb12095.x

31. Scapicchio PL. Revisiting choline alphoscerate profile: a new, perspective, role in dementia? Int J Neurosci. 2013 Jul;123(7):444-9. doi:10.3109/00207454.2013.765870. Epub 2013 Feb 19.

32. Amenta F, Carotenuto A, Fasanaro AM, et al. The ASCOMALVA trial: association between the cholinesterase inhibitor donepezil and the cholinergic precursor choline alphoscerate in Alzheimer's disease with cerebrovascular injury: interim results. J Neurol Sci. 2012;322(1-2):96-101. doi:10.1016/j.jns.2012.07.003

33. Amenta F, Carotenuto A, Fasanaro AM, et al. The ASCOMALVA (Association between the Cholinesterase Inhibitor Donepezil and the Cholinergic Precursor Choline Alphoscerate in Alzheimer's Disease) trial: interim results after two years of treatment. J Alzheimers Dis. 2014;42(Suppl 3):S281-S288. doi:10.3233/JAD-140150

34. Carotenuto A, Rea R, Traini E, et al. The Effect of the Association between Donepezil and Choline Alphoscerate on Behavioral Disturbances in Alzheimer's Disease: Interim Results of the ASCOMALVA Trial. J Alzheimers Dis. 2017;56(2):805-15. doi:10.3233/JAD-160675

35. Traini E, Carotenuto A, Fasanaro AM, Amenta F. Volume Analysis of Brain Cognitive Areas in Alzheimer's Disease: Interim 3-Year Results from the ASCOMALVA Trial. J Alzheimers Dis. 2020;76(1):317-29. doi:10.3233/JAD-190623

36. Nikonov VV, Savitskaya IB, Beletskiy AV. Choline alfoscerate in the treatment of acute ischemic stroke. Meditsina neotlozhnykh sostoyaniy. 2013;(1):68-71 (In Russ.).

37. Kovalchuk VV, Barantsevich YeR. Chronic Cerebral Ischemia. Current Understanding of Etiopathogenesis, Diagnostics and Therapy. Effektivnaya farmakoterapiya. 2017;(19):26-33 (In Russ.).

38. Van der Flier WM, Skoog I, Schneider JA, et al. Vascular cognitive impairment. Nat Rev Dis Primers. 2018 Feb 15;4:18003. doi:10.1038/nrdp.2018.3

39. Gorelick PB, Scuteri A, Black SE, et al.; American Heart Association Stroke Council, Council on Epidemiology and Prevention, Council on Cardiovascular Nursing, Council on Cardiovascular Radiology and Intervention, and Council on Cardiovascular Surgery and Anesthesia. 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

40. Iadecola C, Duering M, Hachinski V, et al. Vascular Cognitive Impairment and Dementia: JACC Scientific Expert Panel. J Am Coll Cardiol. 2019 Jul 2;73(25):3326-44. doi:10.1016/j.jacc.2019.04.034

41. Sweeney MD, Montagne A, Sagare AP, et al. Vascular dysfunction – The disregarded partner of Alzheimer's disease. Alzheimer's Dement. 2019;15:158-6. doi:10.1016/j.jalz.2018.07.222

42. Gottesman RF, Schneider AL, Zhou Y, et al. Association between midlife vascular risk factors and estimated brain amyloid deposition. JAMA. 2017;317:1443-50. doi:10.1001/jama.2017.3090