Pharmacotherapy for dementia

치매의 약물요법

  • Youn, HyunChul (Department of Psychiatry, Korea University Guro Hospital, Korea University College of Medicine) ;
  • Jeong, Hyun-Ghang (Department of Psychiatry, Korea University Guro Hospital, Korea University College of Medicine)
  • 윤현철 (고려대학교 의과대학 고려대학교구로병원 정신건강의학과) ;
  • 정현강 (고려대학교 의과대학 고려대학교구로병원 정신건강의학과)
  • Received : 2018.12.06
  • Accepted : 2018.12.13
  • Published : 2018.12.20


Dementia is a clinical syndrome characterized by a cluster of symptoms and signs that manifest as difficulties in cognitive functions such as memory, psychological and psychiatric changes, and impairments in activities of daily living. As a result of worldwide trends of population aging, dementia has had a huge impact on public health in almost all countries. Disease modification therapies for dementia have not yet been developed. However, pharmacotherapy is essential in patients with dementia to combat delays in their cognitive and functional decline. In this article, we review the current pharmacotherapy for dementia. Three acetylcholinesterase inhibitors-donepezil, rivastigmine, galantamine-and memantine are the only medications that have been approved for the treatment of dementia. We present the indications, dose recommendations, side effects, and criteria for National Health Insurance coverage in Korea of these medications for dementia treatment. Although the Ministry of Food and Drug Safety in Korea has not approved any medications for managing the behavioral and psychological symptoms of dementia, some antipsychotics and antidepressants have been studied and used clinically for those purposes. Clinicians may consider vitamin E, Ginkgo biloba extract, choline alfoscerate, or omega-3 fatty acids as additional treatment options. Non-steroid anti-inflammatory drugs, estrogen hormone therapy, and statins are not generally recommended for dementia treatment. We believe that our findings will aid clinicians in the treatment of patients with cognitive decline.


  1. Jeong HG, Han C. Diagnosis and treatment of dementia in primary care. J Korean Med Assoc 2013;56:1104-1112.
  2. Xu J, Qiu C. Worldwide economic costs and societal burden of dementia. In: Perneczky R, editor. Biomarkers for preclinical Alzheimer's disease. New York: Springer; 2018. p. 3-13.
  3. Ministry of Health and Welfare. Korean dementia observatory 2017. Sejong: Ministry of Health and Welfare; 2017.
  4. Hahn SJ, Paik NJ. Pharmacological treatment of dementia. Brain Neurorehabil 2015;8:19-23.
  5. Francis PT, Palmer AM, Snape M, Wilcock GK. The cholinergic hypothesis of Alzheimer's disease: a review of progress. J Neurol Neurosurg Psychiatry 1999;66:137-147.
  6. Birks J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev 2006;(1):CD005593.
  7. Hansen RA, Gartlehner G, Webb AP, Morgan LC, Moore CG, Jonas DE. Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer's disease: a systematic review and meta-analysis. Clin Interv Aging 2008;3:211-225.
  8. Zhu CW, Livote EE, Scarmeas N, Albert M, Brandt J, Blacker D, Sano M, Stern Y. Long-term associations between cholinesterase inhibitors and memantine use and health outcomes among patients with Alzheimer's disease. Alzheimers Dement 2013;9:733-740.
  9. Courtney C, Farrell D, Gray R, Hills R, Lynch L, Sellwood E, Edwards S, Hardyman W, Raftery J, Crome P, Lendon C, Shaw H, Bentham P; AD2000 Collaborative Group. Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial. Lancet 2004;363:2105-2115.
  10. Korean Association for Geriatric Psychiatry. Geriatric psychiatry. 2nd ed. Seoul: ML Communication; 2015.
  11. Mendez MF, Cummings JL. Dementia: a clinical approach. Philadelphia: Butterworth-Heinemann; 2003.
  12. Ministry of Food and Drug Safety. Online library of medicine [Internet]. Cheongju: Ministry of Food and Drug Safety; 2018 [cited 2018 Nov 1]. Available from:
  13. Farlow MR, Salloway S, Tariot PN, Yardley J, Moline ML, Wang Q, Brand-Schieber E, Zou H, Hsu T, Satlin A. Effectiveness and tolerability of high-dose (23 mg/d) versus standard-dose (10 mg/d) donepezil in moderate to severe Alzheimer's disease: a 24-week, randomized, double-blind study. Clin Ther 2010;32:1234-1251.
  14. Polinsky RJ. Clinical pharmacology of rivastigmine: a new-generation acetylcholinesterase inhibitor for the treatment of Alzheimer's disease. Clin Ther 1998;20:634-647.
  15. Cummings JL, Farlow MR, Meng X, Tekin S, Olin JT. Rivastigmine transdermal patch skin tolerability: results of a 1-year clinical trial in patients with mild-to-moderate Alzheimer's disease. Clin Drug Investig 2010;30:41-49.
  16. Seltzer B. Galantamine-ER for the treatment of mild-to-moderate Alzheimer's disease. Clin Interv Aging 2010;5:1-6.
  17. Wong CW. Pharmacotherapy for dementia: a practical approach to the use of cholinesterase inhibitors and memantine. Drugs Aging 2016;33:451-460.
  18. Deschaintre Y, Richard F, Leys D, Pasquier F. Treatment of vascular risk factors is associated with slower decline in Alzheimer disease. Neurology 2009;73:674-680.
  19. Kerchner GA, Tartaglia MC, Boxer A. Abhorring the vacuum: use of Alzheimer's disease medications in frontotemporal dementia. Expert Rev Neurother 2011;11:709-717.
  20. Ngo J, Holroyd-Leduc JM. Systematic review of recent dementia practice guidelines. Age Ageing 2015;44:25-33.
  21. Tricco AC, Soobiah C, Berliner S, Ho JM, Ng CH, Ashoor HM, Chen MH, Hemmelgarn B, Straus SE. Efficacy and safety of cognitive enhancers for patients with mild cognitive impairment: a systematic review and meta-analysis. CMAJ 2013;185:1393-1401.
  22. Emre M. Switching cholinesterase inhibitors in patients with Alzheimer's disease. Int J Clin Pract Suppl 2002;(127):64-72.
  23. Rogawski MA, Wenk GL. The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease. CNS Drug Rev 2003;9:275-308.
  24. Schneider LS, Dagerman KS, Higgins JP, McShane R. Lack of evidence for the efficacy of memantine in mild Alzheimer disease. Arch Neurol 2011;68:991-998.
  25. Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I; Memantine Study Group. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA 2004;291:317-324.
  26. Howard R, McShane R, Lindesay J, Ritchie C, Baldwin A, Barber R, Burns A, Dening T, Findlay D, Holmes C, Hughes A, Jacoby R, Jones R, Jones R, McKeith I, Macharouthu A, O'Brien J, Passmore P, Sheehan B, Juszczak E, Katona C, Hills R, Knapp M, Ballard C, Brown R, Banerjee S, Onions C, Griffin M, Adams J, Gray R, Johnson T, Bentham P, Phillips P. Donepezil and memantine for moderate-to-severe Alzheimer's disease. N Engl J Med 2012;366:893-903.
  27. Wilkinson D. A review of the effects of memantine on clinical progression in Alzheimer's disease. Int J Geriatr Psychiatry 2012;27:769-776.
  28. Azermai M, Petrovic M, Elseviers MM, Bourgeois J, Van Bortel LM, Vander Stichele RH. Systematic appraisal of dementia guidelines for the management of behavioural and psychological symptoms. Ageing Res Rev 2012;11:78-86.
  29. Trinh NH, Hoblyn J, Mohanty S, Yaffe K. Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: a meta-analysis. JAMA 2003;289:210-216.
  30. Azermai M. Dealing with behavioral and psychological symptoms of dementia: a general overview. Psychol Res Behav Manag 2015;8:181-185.
  31. Wang F, Feng TY, Yang S, Preter M, Zhou JN, Wang XP. Drug therapy for behavioral and psychological symptoms of dementia. Curr Neuropharmacol 2016;14:307-313.
  32. Katz IR, Jeste DV, Mintzer JE, Clyde C, Napolitano J, Brecher M. Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized, double-blind trial. Risperidone Study Group. J Clin Psychiatry 1999;60:107-115.
  33. Bains J, Birks J, Dening T. Antidepressants for treating depression in dementia. Cochrane Database Syst Rev 2002;(4):CD003944.
  34. Tampi RR, Tampi DJ. Efficacy and tolerability of benzodiazepines for the treatment of behavioral and psychological symptoms of dementia: a systematic review of randomized controlled trials. Am J Alzheimers Dis Other Demen 2014;29:565-574.
  35. Pinheiro D. [Anticonvulsant mood stabilizers in the treatment of behavioral and psychological symptoms of dementia (BPSD)]. Encephale 2008;34:409-415.
  36. Farina N, Llewellyn D, Isaac MG, Tabet N. Vitamin E for Alzheimer's dementia and mild cognitive impairment. Cochrane Database Syst Rev 2017;1:CD002854.
  37. Dysken MW, Sano M, Asthana S, Vertrees JE, Pallaki M, Llorente M, Love S, Schellenberg GD, McCarten JR, Malphurs J, Prieto S, Chen P, Loreck DJ, Trapp G, Bakshi RS, Mintzer JE, Heidebrink JL, Vidal-Cardona A, Arroyo LM, Cruz AR, Zachariah S, Kowall NW, Chopra MP, Craft S, Thielke S, Turvey CL, Woodman C, Monnell KA, Gordon K, Tomaska J, Segal Y, Peduzzi PN, Guarino PD. Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial. JAMA 2014;311:33-44.
  38. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev 2012;(3):CD007176.
  39. Yuan Q, Wang CW, Shi J, Lin ZX. Effects of Ginkgo biloba on dementia: an overview of systematic reviews. J Ethnopharmacol 2017;195:1-9.
  40. Scapicchio PL. Revisiting choline alphoscerate profile: a new, perspective, role in dementia? Int J Neurosci 2013;123:444-449.
  41. Gavrilova SI, Kolykhalov IV, Ponomareva EV, Fedorova YB, Selezneva ND. Clinical efficacy and safety of choline alfoscerate in the treatment of late-onset cognitive impairment. Zh Nevrol Psikhiatr Im S S Korsakova 2018;118:45-53.
  42. Burckhardt M, Herke M, Wustmann T, Watzke S, Langer G, Fink A. Omega-3 fatty acids for the treatment of dementia. Cochrane Database Syst Rev 2016;4:CD009002.
  43. Mulnard RA, Cotman CW, Kawas C, van Dyck CH, Sano M, Doody R, Koss E, Pfeiffer E, Jin S, Gamst A, Grundman M, Thomas R, Thal LJ. Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. Alzheimer's Disease Cooperative Study. JAMA 2000;283:1007-1015.
  44. Maki PM, Henderson VW. Hormone therapy, dementia, and cognition: the Women's Health Initiative 10 years on. Climacteric 2012;15:256-262.
  45. King DS, Wilburn AJ, Wofford MR, Harrell TK, Lindley BJ, Jones DW. Cognitive impairment associated with atorvastatin and simvastatin. Pharmacotherapy 2003;23:1663-1667.