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Vol. 23, No. 3, 2007
Issue release date: February 2007
Dement Geriatr Cogn Disord 2007;23:150–160

Donepezil in Alzheimer’s Disease: What to Expect after 3 Years of Treatment in a Routine Clinical Setting

Wallin Å.K. · Andreasen N. · Eriksson S. · Båtsman S. · Näsman B. · Ekdahl A. · Kilander L. · Grut M. · Rydén M. · Wallin A. · Jonsson M. · Olofsson H. · Londos E. · Wattmo C. · Eriksdotter Jönhagen M. · Minthon L.
aClinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Malmö, bKarolinska Institutet, Alzheimer’s Disease Research Center, Department of Neurotec, Division of Geriatric Medicine, Karolinska University Hospital, Huddinge, Stockholm, cSection of Geriatric Medicine, Department of Community Medicine and Rehabilitation, Umeå University, Umeå, dDepartment of Primary Care, Kalix Vårdcentral, Kalix, eDepartment of Geriatric Medicine University Hospital Linköping, Linköping, fDepartment of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, gDepartment of Geriatric Medicine, Cognitive Section Danderyd Hospital, Danderyd, hInstitute of Neuroscience, Section of Psychiatry, Göteborg/Sahlgrenska University Hospital, Mölndal, and iMemory Clinic, Uddevalla Hospital, Uddevalla, Sweden

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Background/Aims: Clinical short-term trails have shown positive effects of donepezil treatment in patients with Alzheimer’s disease. The outcome of continuous long-term treatment in the routine clinical settings remains to be investigated. Methods: The Swedish Alzheimer Treatment Study (SATS) is a descriptive, prospective, longitudinal, multicentre study. Four hundred and thirty-five outpatients with the clinical diagnosis of Alzheimer’s disease, received treatment with donepezil. Patients were assessed with Mini-Mental State Examination (MMSE), Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog), global rating (CIBIC) and Instrumental Activities of Daily Living (IADL) at baseline and every 6 months for a total period of 3 years. Results: The mean MMSE change from baseline was positive for more than 6 months and in subgroups of patients for 12 months. After 3 years of treatment the mean change from baseline in MMSE-score was 3.8 points (95% CI, 3.0–4.7) and the ADAS-cog rise was 8.2 points (95% CI, 6.4–10.1). This is better than expected in untreated historical cohorts, and better than the ADAS-cog rise calculated by the Stern equation (15.6 points; 95% CI, 14.5–16.6). After 3 years with 38% of the patients remaining, 30% of the them were unchanged or improved in the global assessment. Conclusion: Three-year donepezil treatment showed a positive global and cognitive outcome in the routine clinical setting.

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  1. Fratiglioni L, Launer LJ, Andersen K, Breteler MMB, Copeland JRM, Dartigues J-F, Lobo A, Martinez-Lage J, Soininen H, Hofman A: Incidence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology 2000;54(suppl 5):10–15.
  2. Galasko D, Edland SD, Morris JC, Clark C, Mohs R, Koss E: The consortium to establish a registry for Alzheimer’s disease (CERAD). XI. Clinical milestones in patients with Alzheimer’s disease followed over 3 years. Neurology 1995;45:1451–1455.
  3. Rossor MN, Garrett NJ, Johnson AL, Mountjoy CQ, Roth M, Iversen LL: A post-mortem study of the cholinergic and GABA systems in senile dementia. Brain 1982;105:313–330.
  4. Bird TD, Stranahan S, Sumi SM, Raskind M: Alzheimer’s disease: choline acetyltransferase activity in brain tissue from clinical and pathological subgroups. Ann Neurol 1983;14:284–293.
  5. Cummings JL, Donohue JA, Brooks RL: The relationship between donepezil and behavioral disturbances in patients with Alzheimer’s disease. Am J Geriatr Psychiatry 2000;8:134–140.
  6. Whitehouse PJ: The cholinergic deficit in Alzheimer’s disease. J Clin Psychiatry 1998;59(suppl 13):19–22.

    External Resources

  7. Perry EK, Tomlinson BE, Blessed G, Bergmann K, Gibson PH, Perry RH: Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. BMJ 1978;2:1457–1459.
  8. Knapp MJ, Knopman DS, Solomon PR, Pendlebury WW, Davis CS, Gracon SI: A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer’s disease. The Tacrine Study Group. JAMA 1994;271:985–991.
  9. Harvey RJ, Eagger SA: The clinical efficacy of tacrine. Rev Contemp Pharmacother 1995;6:335–348.
  10. Winblad B, Engedal K, Soininen H, Verhey F, Waldemar G, Wimo A, Wetterholm A-L, Zhang R, Haglund A, Subbiah P; Donepezil Nordic Study Group: A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD. Neurology 2001;57:489–495.
  11. Doody RS, Geldmacher DS, Gordon B, Perdomo CA, Pratt RD; Donepezil Study Group: Open-label, multicenter, phase 3 extension study of the safety and efficacy of donepezil in patients with Alzheimer disease. Arch Neurol 2001;58:427–433.
  12. Birks JS, Harvey R: Donepezil for dementia due to Alzheimer’s disease (Cochrane Review); in The Cochrane Library. Chichester, Wiley, 2005.
  13. Trinh N-H, Hoblyn J, Mohanty S, Yaffe K: Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer’s disease: a meta-analysis. JAMA 2003;289:210–216.
  14. Cummings JL: Use of cholinesterase inhibitors in clinical practice: evidence-based recommendations. Am J Geriatr Psychiatry 2003;11:131–145.
  15. Ritchie CW, Ames D, Clayton T: Metaanalysis of randomized trials of the efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer’s disease. Am J Geriatr Psychiatry 2004;12:358–368.
  16. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders DSM-IV Fourth Edition. Washington, American Psychiatric Publishing, 1994.
  17. McKhann G, Drachman DA, Folstein MF, Katzman R, Prince D, Stadlan EM: Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA work group under the auspices of the Department of Health and Human Services task force on Alzheimer’s disease. Neurology 1984;34:939–944.
  18. 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;12:189–198.
  19. Rosen WG, Mohs RC, Davis KL: A new rating scale for Alzheimer’s disease. Am J Psychiatry 1984;141:1356–1364.
  20. Knopman DS, Knapp MJ, Gracon SI, Davis CS: The Clinician Interview-Based Impression (CIBI): a clinician’s global change rating scale in Alzheimer’s disease. Neurology 1994;44:2315–2321.
  21. Schneider LS, Olin JT, Doody RS, Clark CM, Morris JC, Riesberg B, Schmitt FA, Grundman M, Thomas RG, Ferris SH: Validity and reliability of the Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change. The Alzheimer’s Disease Cooperative Study. Alzheimer Dis Assoc Disord 1997;11(suppl 2):22–32.

    External Resources

  22. Lawton MP, Brody EM: Assessments of older people: self-maintaining and instrumental activities of daily living. Gerontologist 1969;9:179–186.
  23. Stern RG, Mohs RC, Davidson M, Schmeidler J, Silverman J, Kramer-Ginsberg E, Searcey T, Bierer L, Davis KL: A longitudinal study of Alzheimer’s disease: Measurement, rate and predictors of cognitive deterioration. Am J Psychiatry 1994;151:390–396.
  24. Han L, Cole M, Bellavance F, McCusker J, Primeau F: Tracking cognitive decline in Alzheimer’s disease using the Mini-Mental State Examination: a meta-analysis. Int Psychogeriatr 2000;12:231–247.
  25. Salmon DP, Thal LJ, Butters N, Heindel WC: Longitudinal evaluation of dementia of the Alzheimer type: a comparison of 3 standardized mental status examinations. Neurology 1990;40:1225–1230.
  26. Mendiondo MS, Ashford JW, Kryscio RJ, Schmitt FA: Modelling mini mental state examination changes in Alzheimer’s disease. Stat Med 2000;19:1607–1616.
  27. AD2000 Collaborative Group: Long-term donepezil treatment in 565 patients with Alzheimer’s disease (AD2000): randomised double-blind trial. Lancet 2004;363:2105–2115.
  28. Yesavage JA, Poulsen AB, Sheikh J, Tanke E: Rates of change of common measures of impairment in senile dementia of the Alzheimer’s type. Psychopharmacol Bull 1988;24:531–534.
  29. Rogers SL, Doody RS, Pratt RD, Ieni JR: Long-term efficacy and safety of donepezil in the treatment of Alzheimer’s disease: final analysis of a US multicentre open-label study. Eur Neuropsychopharmacol 2000;10:195–203.
  30. Truyen L, Lilienfeld S, Kershaw P: Safety and efficacy of galatamine in Alzheimer’s disease after treatment for 4 years. Poster 2002.
  31. Grossberg G, Irwin P, Satlin A, Mesenbrink P, Spiegel R: Rivastigmine in Alzheimer disease – efficacy over two years. Am J Geriatr Psychiatry 2004;12:420–431.
  32. Pirtilla T, Wilcock G, Truyen L, Damaraju CV: Long-term efficacy and safety of galantamine in patients with mild-to-moderate Alzheimer’s disease: multicenter trial. Eur J Neurol 2004;11:734–741.
  33. Raskind MA, Peskind ER, Truyen L, Kershaw P, Damaraju CV: The cognitive benefits of galantamine are sustained for at least 36 months: a long-term extension trial. Arch Neurol 2004;61:252–256.
  34. Small GW, Kaufer D, Mendiondo MS, Quarg P, Spiegel R: Cognitive performance in Alzheimer’s disease patients receiving rivastigmine for up to 5 years. Int J Clin Pract 2005;59:473–477.
  35. Winblad B, Wimo A, Engedal K, Soininen H, Verhey F, Waldemar G, Wetterholm A-L, Haglund A, Zhang R, Schindler R; Donepezil Nordic Study Group: 3-year study of donepezil therapy in Alzheimer’s disease: effects of early and continuous therapy. Dement Geriatr Cogn Disord 2006;21:353–363.
  36. Quinn J, Moore M, Benson DF: A videotaped CIBIC for dementia patients: validity and reliability in a simulated clinical trial. Neurology 2002;58:433–437.
  37. Johannsen P: Long-term cholinesterase inhibitor treatment of Alzheimer’s disease. CNS Drugs 2004;18:757–768.
  38. Kurz A, Farlow M, Quarg P, Spiegel R: Disease stage in Alzheimer disease and treatment effects of rivastigmine. Alzheimer Dis Assoc Disord 2004;18:123–128.
  39. López-Pousa S, Turon-Estrada A, Garre-Olmo J, Pericot-NIerga I, Lozano-Gallego M, Vilalta-Franch M, Hernández-Ferràndiz M, Morante-Munoz V, Isern-Vila A, Gelada-Batlle E, Majó-Llopart J: Differential efficacy of treatment with acetylcholinesterase inhibitors in patients with mild and moderate Alzheimer’s disease over a 6-month period. Dement Geriatr Cogn Disord 2005;19:189–195.
  40. Connelly PJ, Prentice NP, Fowler KG: Predicting the outcome of cholinesterase inhibitor treatment in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2005;76:320–324.
  41. Minthon L, Gustafson L, Dahlfelt G, Hagberg B, Risberg J, Rosén I, Seiving B, Wendt PE: Oral tetrahydroaminoacridine treatment of Alzheimer’s disease evaluated clinically and by regional cerebral blood flow and EEG. Dement Geriatr Cogn Disord 1993;4:32–42.
  42. Feldman H, Gauthier S, Hecker J, Vellas B, Emir B, Mastey V, Subbiah P; Donepezil MSAD Study Investigators Group: Efficacy of donepezil on maintenance of activities of daily living in patients with moderate to severe Alzheimer’s disease and the effect on caregiver burden. J Am Geriatr Soc 2003;51:737–744.
  43. Waldemar G: Donepezil in the treatment of patients with Alzheimer’s disease. Expert Rev Neurother 2001;1:11–19.
  44. Wallin ÅK, Gustafson L, Sjögren M, Wattmo C, Minthon L: Five-year outcome of cholinergic treatment of Alzheimer’s disease: early response predicts prolonged time until nursing home placement, but does not alter life expectancy. Dement Geriatr Cogn Disord 2004;18:197–206.
  45. Birks J: Cholinesterase inhibitors for Alzheimer’s disease. The Cochrane Database of Systematic Reviews 2006.

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