The Effects of Donepezil, Galantamine, Rivastigmine and Memantine on Mini-Mental State Examination and Mean Flow Velocity in Patients with Vascular Dementia: A Double-Blinded Randomized Clinical Trial

Document Type: Original Article


1 Professor of Neurology, Stroke fellowship, Neurology Research Center, Kerman University of Medical Sciences, Kerman, Iran

2 Assistant Professor of Neurology, Neurology Research Center, Kerman University of Medical Sciences, Kerman, Iran

3 Neurologist, Neurology Research Center, Kerman University of Medical sciences, Kerman, Iran


Background: Vascular dementia is one of the most common forms of dementia. At now, there is no treatment available to cure vascular dementia or to alter its clinical course. Some studies suggest that some drugs may be useful in controlling symptoms. The aim of this study was to evaluate the effects of donepezil, memantine, rivastigmine and galantamine on mean flow velocity and Mini-Mental State Examination of patients with vascular dementia in a three- month follow-up period.
Methods: This double-blind clinical trial was conducted on 44 patients with vascular dementia. Vascular dementia was diagnosed based on the DSM-V criteria. According to the order of entry into the study, the participants were treated with one of the selected drugs [donepezil (10 mg/d), memantine (10 mg/d), galantamine (8 mg/d) and rivastigmine (6 mg/d)]. The sampling finished whenever 11 patients in each group completed the three-month trial. The MMSE and color Doppler ultrasound was performed for all participants before and three months after the intervention.
Results: According to the findings, there was no significant difference among the groups in the frequency of variables and the mean scores of Mini-Mental State Examination before the intervention, but the administration of memantine and donepezil significantly increased Mini-Mental State Examination score (P = 0.009 and P = 0.001 respectively). Moreover, rivastigmine, galantamin and donepezil significantly increased mean flow velocity in some arteries.
Discussion: Memantine and donepazil improve cognitive function in patients with vascular dementia. Rivastigmine, galantamin and donepezil have some effects on cerebral blood flow.


  1. Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement 2013; 9(1):63-75.e2.
  2. Birks J, McGuinness B, Craig D. Rivastigmine for vascular cognitive impairment. Cochrane Database Syst Rev 2013; 5:CD004744.
  3. Farooq MU, Min J, Goshgarian C, Gorelick PB. Pharmacotherapy for vascular cognitive impairment. CNS Drugs 2017; 31(9):759-76.
  4. Malouf R, Birks J. Donepezil for vascular cognitive impairment. Cochrane Database Syst Rev 2004; (1):CD004395.
  5. Moretti R, Torre P, Antonello RM, Cazzato G, Bava A. Rivastigmine in subcortical vascular dementia: an open 22-month study. J Neurol Sci 2002; 203-204:141-6.
  6. Liu Q, Wang XJ, Zhang ZC, Xue R, Li P, Li B. Neuroprotection against vascular dementia after acupuncture combined with donepezil hydrochloride: P300 event related potential. Neural Regen Res 2016; 11(3):460-4.
  7. Servello A, Andreozzi P, Bechini F, De Angelis R, Pontecorvo ML, Vulcano A, et al. Effect of AChE and BuChE inhibition by rivastigmin in a group of old-old elderly patients with cerebrovascular impairment (SIVD type). Minerva Med 2014; 105(2):167-74. [In Italian].
  8. Kandiah N, Pai MC, Senanarong V, Looi I, Ampil E, Park KW, et al. Rivastigmine: the advantages of dual inhibition of acetylcholinesterase and butyrylcholinesterase and its role in subcortical vascular dementia and Parkinson's disease dementia. Clin Interv Aging 2017; 12:697-707.
  9. Chen YD, Zhang J, Wang Y, Yuan JL, Hu WL. Efficacy of cholinesterase inhibitors in vascular dementia: an updated meta-analysis. Eur Neurol 2016; 75(3-4):132-41.
  10. Wang F, Zou Z, Gong Y, Yuan D, Chen X, Sun T. Regulation of human brain microvascular endothelial cell adhesion and barrier functions by memantine. J Mol Neurosci 2017; 62(1):123-29.
  11. Ghorbani A, Chitsaz A, Shishegar M, Akbari M. Evaluation the effect of donepezil on cerebral blood flow velocity in alzheimer's disease. Neurosciences (Riyadh) 2010; 15(3):172-6.
  12. D'Andrea A, Conte M, Scarafile R, Riegler L, Cocchia R, Pezzullo E, et al. Transcranial doppler ultrasound: physical principles and principal applications in neurocritical care unit. J Cardiovasc Echogr 2016; 26(2):28-41.
  13. Purkayastha S, Sorond F. Transcranial doppler ultrasound: technique and application. Semin Neurol 2012; 32(4):411-20.
  14. Sinha P, Bharath S, Chandra SR. DSM-5 in Vascular Dementia- Comparison with other diagnostic criteria in a retrospective study. EC Neurology 2015; 2(3):135-43.
  15. Seifaddini R, Hamze Moghadam A, Iranmanesh F, Arvan H, Naghibzadeh-Tahami A. The effects of citicoline on cerebrovascular hemodynamic status in ischemic stroke patients. Journal of Kerman University of Medical Sciences 2017; 24(6):480-6.
  16. Wilkinson D, Doody R, Helme R, Taubman K, Mintzer J, Kertesz A, et al. Donepezil in vascular dementia: a randomized, placebo-controlled study. Neurology 2003; 61(4):479-86.
  17. Black S, Román GC, Geldmacher DS, Salloway S, Hecker J, Burns A, et al. Efficacy and tolerability of donepezil in vascular dementia: positive results of a 24-week, multicenter, international, randomized, placebo-controlled clinical trial. Stroke 2003; 34(10):2323-30.
  18. Román GC, Salloway S, Black SE, Royall DR, Decarli C, Weiner MW, et al. Randomized, placebo-controlled, clinical trial of donepezil in vascular dementia: differential effects by hippocampal size. Stroke 2010; 41(6):1213-21.
  19. Dichgans M, Markus HS, Salloway S, Verkkoniemi A, Moline M, Wang Q, et al. Donepezil in patients with subcortical vascular cognitive impairment: a randomised double-blind trial in CADASIL. Lancet Neurol 2008; 7(4):310-8.
  20. Wilcock G, Möbius HJ, Stöffler A, MMM 500 group. A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM500). Int Clin Psychopharmacol 2002; 17(6):297-305.
  21. Orgogozo JM, Rigaud AS, Stöffler A, Möbius HJ, Forette F. Efficacy and safety of memantine in patients with mild to moderate vascular dementia: a randomized, placebo-controlled trial (MMM 300). Stroke 2002; 33(7):1834-9.
  22. Erkinjuntti T, Kurz A, Gauthier S, Bullock R, Lilienfeld S, Damaraju CV. Efficacy of galantamine in probable vascular dementia and Alzheimer's disease combined with cerebrovascular disease: a randomised trial. Lancet 2002; 359(9314):1283-90.
  23. Auchus AP, Brashear HR, Salloway S, Korczyn AD, De Deyn PP, Gassmann-Mayer C, et al. Galantamine treatment of vascular dementia: a randomized trial. Neurology 2007; 69(5):448-58.
  24. Ballard C, Sauter M, Scheltens P, He Y, Barkhof F, van Straaten EC, et al. Efficacy, safety and tolerability of rivastigmine capsules in patients with probable vascular dementia: the VantagE study. Curr Med Res Opin 2008; 24(9):2561-74.
  25. Mok V, Wong A, Ho S, Leung T, Lam WW, Wong KS. Rivastigmine in Chinese patients with subcortical vascular dementia. Neuropsychiatr Dis Treat 2007; 3(6):943-8.
  26. Narasimhalu K, Effendy S, Sim CH, Lee JM, Chen I, Hia SB, et al. A randomized controlled trial of rivastigmine in patients with cognitive impairment no dementia because of cerebrovascular disease. Acta Neurol Scand 2010; 121(4):217-24.
  27. Jin BR, Liu HY. Comparative efficacy and safety of cognitive enhancers for treating vascular cognitive impairment: systematic review and Bayesian network meta-analysis. Neural Regen Res 2019; 14(5):805-16.