Cholinesterase inhibitors for Alzheimer's disease

Jacqueline S Birks

doi:10.1002/14651858.CD005593

Inhibidores de la colinesterasa para la enfermedad de Alzheimer

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Referencias de los estudios incluidos en esta revisión

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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. Archives of Neurology 2001;58(3):427‐33.

Feldman H. Gauthier S. Hecker J. Vellas B. Subbiah P. Whalen E. Donepezil MSAD Study Investigators Group. Erratum: a 24‐week, randomized, double‐blind study of donepezil in moderate to severe alzheimer's disease. Neurology2001; Vol. 57, issue 11:2153.

Friedhoff LT, Rogers L. Donepezil lengthens time to loss of activities of daily living in patients with mild to moderate Alzheimer's disease ‐ results of a preliminary evaluation. Presented at the annual meeting of the American Academy of Neurology. Boston. Neurology 1997;48(3):A100.

Google Scholar

Friedhoff LT, Rogers SL. Donepezil lengthens time to loss of activities of daily living and cognition in patients with mild to moderate Alzheimer's disease. Proceedings of the 10th European College of Neuropsychopharmacology Congress; 1997 Sep 13‐17, Vienna, Austria1997. [MEDLINE: SR‐HANDSRCH]

Google Scholar

Friedhoff LT, Rogers SL. Donepezil maintains activities of daily living in patients with mild to moderately severe Alzheimer's disease: results of a retrospective analysis. Eur J Neurology 1997;4, Suppl 1:S9.

Google Scholar

Rogers SL. Donepezil new clinical trials support long term use. Proceedings of the Sixth International Stockholm/Springfield Symposium on Advances in Alzheimer Therapy; 2000 Apr 5‐8, Stockholm. 2000:133.

Google Scholar

Rogers SL, Doody R, Mohs R, Friedhoff LT. E2020 produces both clinical, global and cognitive test improvement in patients with mild to moderately severe Alzheimer's disease: Results of a 30‐week phase III trial. Neurology 1996;46:A217 S14.001 ARI‐8.

Google Scholar

Rogers SL, Doody R, Mohs R, Friedhoff T, Donepezil Study Group. E2020 (Aricept TM) improves global and cognitive function in patients with Alzheimer's Disease. Results of a 30‐week trial. unpublished paper1996b.

Google Scholar

Rogers SL, Farlow MR, Doody RS, Mohs R, Friedhoff LT, and the Donepezil Study Group. A 24‐week, double‐blind, placebo‐controlled trial of donepezil in patients with Alzheimer's disease. Neurology 1998;50(1):136‐145.

Rogers SL, Friedhoff LT, Farlow MR, Doody RS, Mohs R. Efficacy of donepezil in Alzheimer's disease: Fact or artifact? [Reply]. Neurology1999; Vol. 52, issue 1:218‐9.

Google Scholar

Rogers SL, Mohs RC, Friedhoff LT. Donepezil (E2020) improves cognition and function in patients with mild to moderately severe Alzheimer's disease. Results from Phase III trials. American Psychiatric Association 150th Annual Meeting, San Diego1997.

Google Scholar

Bayer AJ, Rossor M, Hecker J, Gauthier S, Burns A, Petite H, Moller HJ, Rogers SL, Friedhoff LT, International Donepezil Study Group. Donepezil improves functional activity in patients with Alzheimer's disease. Proceedings of the 21st Collegium Internationale Neuro psychopharmacologicum; 1998 Jul 12‐16, Glasgow, Scotland1998. [MEDLINE: SR‐HANDSRCH]

Google Scholar

Burns A, Rossor M, Hecker J, Gauthier S, Petit H, Möller H‐J, Rogers SL, Friedhoff LT and the International Donepezil Study Group. The effects of donepezil in Alzheimer's disease ‐ results from a multinational trial. Dement Geriatr Cogn Disord 1999;10(3):237‐244.

Gauthier S, Rosser M, Hecker J, Petite H, Rogers S, Mohr E, Burns A, Friedhoff LT, Rogers S. Donepezil Produces Both Clinical Global and Cognitive Test Improvement in Patients with Alzheimer's Disease. Proceedings of the 151st Annual Meeting of the American Psychiatric Association; 1998 May 30‐Jun 4, Toronto, Canada1998b. [MEDLINE: SR‐HANDSRCH]

Google Scholar

Gauthier S, Rossor M, Hecker J, et al. Results from a multinational Phase III clinical trial of donepezil in Alzheimer's disease. [abstract] [poster presentation at 5th International Geneva/Springfield Symposium on Advances in Alzheimer therapy] April 15‐18 1998.

Pratt RD, Gauthier S, Burns A, Perdomo CA. Donepezil provides long‐term clinical benefits for patients with Alzheimers Disease. Proceedings of the World Alzheimer Congress; 2000 Jul 9‐13, Washington2000a.

Google Scholar

Finucane TE, Tariot PN, Cummings JL, Katz IR, Mintzer J, Perdomo CA, Schwam EM, Whalen E. Getting donepezil into the nursing home. A randomized, double‐blind, placebo‐controlled study of the efficacy and safety of donepezil in patients with Alzheimer's disease in the nursing home setting. Journal of the American Geriatrics Society2003; Vol. 51, issue 1:133‐134.

Google Scholar

Steinman MA, Covinsky KE, Tariot PN, Cummings JL, Katz IR, Mintzer J, Perdomo CA, Schwam EM, Whalen E. Donepezil for nursing home patients with dementia: a reinterpretation of the evidence. A randomized, double‐blind, placebo‐controlled study of the efficacy and safety of donepezil in patients with Alzheimer's disease in the nursing home setting J Am Geriatr Soc 2001;49:1590‐9.. Journal of the American Geriatrics Society 2003;51(1):132‐133.

Tariot P, Cummings JL, Katz IR, Perdomo CA, Whalen E, Sovel MA, Schwam EM. Donepezil was well‐tolerated and enhanced cognition in nursing home patients with alzheimer's disease. Journal of the American Geriatrics Society1999; Vol. 47:S3.

Google Scholar

Tariot P, Perdomo CA, Whalen E, Sovel MA, Scham EM. Age is not a barrier to donepezil treatment of Alzheimer's disease in the long‐term care setting. International Psychogeriatrics. 1999; Vol. 11, issue Supplement 1:134.

Google Scholar

Tariot PN, Cummings JL, Katz IR, Mintzer J, Perdomo CA, Schwam EM, Whalen E. A randomised, double‐blind, placebo‐controlled study of the efficacy and safety of Donepezil in patients with Alzheimer's disease in the nursing home setting. Journal of the American Geriatrics Society2001; Vol. 49, issue 12:1590‐9.

Google Scholar

Seltzer B, Zolnouni P, Nunez M, Goldman R, Kumar D, Ieni J, Richardson S, Donepezil 402 Study Group. Efficacy of donepezil in early‐stage Alzheimer disease. Archives of Neurolology 2004;61:1852‐6.

Feldman H. Therapeutic benefits of acetylcholinesterase inhibitor therapy in the moderate to severe stage of alzheimer's disease. Proceedings of the Sixth International Stockholm/Springfield Symposium on Advances in Alzheimer Therapy; 2000 Apr 5‐8, Stockholm2000:59.

Google Scholar

Feldman H, Gauthier S, Hecker J, Vellas B, Hux M, Emir B, Subbiah P, Mastery V. Improved health outcomes with donepezil in moderate to severe Alzheimer's disease are associated with economic benefits. The 8th conference on Alzheimer's disease and related disorders, July 20‐25, 2002, Stockholm, Sweden. 2002:285.

Google Scholar

Feldman H, Gauthier S, Hecker J, Vellas B, Emir B, Mastey V, Subbiah P, and the Donepezil Study 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. Journal of the American Geriatrics Society 2003;51:737‐744.

Feldman H, Gauthier S, Hecker J, Vellas B, Hux M, Xu Y, Schwam EM, Shah S, Mastey V, Donepezil MSAD Study Investigators Group. Economic evaluation of donepezil in moderate to severe Alzheimer disease. Neurology 2004;63(4):644‐650.

Feldman H, Gauthier S, Hecker J, Vellas B, Ieni J, Xu Y, Schwam E. Treatment Benefits of Donepezil in Patients with Severe Alzheimer's Disease and Their Caregivers. 57th Annual Meeting of the American Academy of Neurology, Miami Beach, April 2005 2005b:P02.097. 2005.

Google Scholar

Feldman H, Gauthier S, Hecker J, Vellas B, Subbiah P, Whalen E. Donepezil provides benefits in global function in moderate to severe Alzheimer's Disease. Proceedings of the World Alzheimer Congress; 2000 Jul 9‐13, Washington DC2000.

Google Scholar

Feldman H, Gauthier S, Hecker J, Vellas B, Subbiah P, Whalen E. Donepezil's benefits on cognition, global function, activities of daily living and behavior in patients with moderate to severe alzheimer's disease. Proceedings of the Sixth International Stockholm/Springfield Symposium on Advances in Alzheimer Therapy; 2000 Apr 5‐8, Stockholm2000:174.

Google Scholar

Feldman H, Gauthier S, Hecker J, Vellas B, Subbiah P, Whalen E, Donepezil MSAD Study Group. Benefits of Donepezil on global function, behavior, cognition and ADLs in patients with moderate to severe Alzheimer's disease. Neurology2000; Vol. 54, issue Suppl 3:A469.

Google Scholar

Feldman H, Gauthier S, Hecker J, Vellas B, Subbiah P, Whalen E, Donepezil MSAD Study Investigators Group. A 24‐week, randomized, double‐blind study of donepezil in moderate to severe Alzheimer's disease. Neurology2001a; Vol. 57, issue 4:613‐20.

Google Scholar

Gauthier S, Feldman H, Hecker J, Vellas B, Emir B, McGill PS. Exploratory analysis of the effects af donepezil in moderate and severe Alzheimer's disease patients. The 8th conference on Alzheimer's disease and related disorders, July 20‐25, 2002, Stockholm, Sweden2002:277.

Google Scholar

Gauthier S, Feldman H, Hecker J, Vellas B, Ames D, Subbiah P, Whalen E, Emir B, Donepezil MSAD Study Investigators Group. Efficacy of donepezil on behavioral symptoms in patients with moderate to severe Alzheimer's disease. International Psychogeriatrics 2002;14(4):389‐404.

Gauthier S, Feldman H, Hecker J, Vellas B, Emir B, Subbiah P, The Donepezil MSAD Study Investigators' Group. . 2002a, 18(6):347‐54. Functional, cognitive and behavioral effects of donepezil in patients with moderate Alzheimer's disease. Dementia and Geriatric Cognitive Disorders 2002;18(6):347‐354.

Google Scholar

Gauthier S, Feldman H, Hecker J, Vellas B, Subbiah P, Whalen E. Benefits of Donepezil on performance of basic and instrumental activities of daily living in moderate to sever Alzheimer's Disease. Proceedings of the World Alzheimer Congress; 2000 Jul 9‐13, Washington DC2000a.

Google Scholar

Gauthier S, Feldman H, Hecker J, Vellas B, Subbiah P, Whalen E. Effects of donepezil on behaviour and other domains in moderate to severe alzheimer's disease. Journal of the European College of Neuropsychopharmacology. 2000b; Vol. 10, issue Suppl 3:S359. [MEDLINE: SR‐HANDSRCH]

Google Scholar

Gauthier S, Feldman H, Vellas B, Subbiah P. Efficacy of donepezil on functional, behavioural and cognitive symptoms in patients with moderate to severe alzheimer's disease. Journal of the American Geriatrics Society2000; Vol. 48, issue 8:S2.

Google Scholar

Hecker J, Foti D, Gauthier S, Vellas B, Subbiah P, Whalen E. Benefits of Donepezil in the treatment of behavioural problems in moderate to severe Alzheimer's Disease. Proceedings of the World Alzheimer Congress; 2000 Jul 9‐13, Washington DC2000.

Google Scholar

Luckmann R. Donepezil improved the clinical state and quality of life in moderate‐to‐severe Alzheimer disease. ACP‐Journal‐Club2002; Vol. 136, issue 2:59.

Google Scholar

Panisset M, Feldman H, Gauthier S, Hecker J, Vellas B, Subbiah P, Whalen E. Use of the severe impairment battery in a clinical trial of Donepezil in moderate to severe Alzheimers Disease. Proceedings of the World Alzheimer Congress; 2000 Jul 9‐13, Washington2000.

Google Scholar

Shah SN, Feldman H, Gauthier S, Hecker J, Vellas B, Hux M, Xu Y, Schwam E, Leaderer M, Pfizer Inc, New York, NY, USA. Pharmacoeconomic Benefits of Donepezil Treatment in Severe Alzheimer's Disease. NeuroBiology of Aging 2004;25(S2):208.

Vellas B, Feldman H, Gauthier S, Hecker J, Subbiah P, Whalen E, Mastey V. Donepezil treatment in patients with moderate to severe Alzheimer's Disease reduces caregiver stress. Proceedings of the World Alzheimer Congress; 2000 Jul 9‐13, Washington2000.

Google Scholar

Engedal K, Soininen H, Verhey F, Waldemar G, Winblad B, Wimo A, Wetterholm AL, Zhang R, Haglund A, Subbiah P. Donepezil improved or stabilized cognition over one year in patients with mild and moderate alzheimer's disease. Journal of the European College of Neuropsychopharmacology 2000;10(Suppl 3):S368.

Mastey V, Wimo A, Winblad B, Haglund A, Jacobson L, Miceli R, Zhang R, Subbiah P. An economic evaluation of donepezil in mild to moderate alzheimer's disease: results of a one year, double‐blind, randomized trial. Journal of the American Geriatrics Society 2001;49(4):S131.

Google Scholar

Mastey V, Wimo A, Winblad B, Haglund A, Jacobson L, Miceli R, Zhang R, Subbiah P. Donepezil reduces the time caregivers spend providing care: results of a one‐year, double‐blind, randomized trial in patients with mild to moderate Alzheimer's disease. Proceedings of the 14th Annual Meeting of the American Association for Geriatric Psychiatry; 2001 Feb 23‐26, San Francisco2001.

Google Scholar

Soininen H, Winblad B, Engedal K, Verhey F, Waldemar G, Wimo A, Wetterholme AL, Zhang R, Hugland A, Subbiah P. Long term benefits of donepezil on ADLs in AD patients. Proceedings of the Annual Scientific Meeting of the American Geriatric Society and the American Federation for Aging Research; 2000 May 17‐21, Nashville.2000:171.

Google Scholar

Soininen H, Winblad B, Engedal K, Verhey F, Waldemar G, Wimo A, Zhang R, Subbiah P, Donepezil Nordic Study Group. Response to Donepezil is not predicted by apolipoprotein E genotype and/or gender. Proceedings of the World Alzheimer Congress; 2000 Jul 9‐13, Washington2000.

Google Scholar

Waldemar G, Winblad B, Engedal K, Soininen H, Donepezil Nordic Study Group et al. Benefits of Donepezil on cognition, function and/or neuropsychiatric symtoms in patients with Alzheimers Disease over one year. Proceedings of the World Alzheimer Congress; 2000 Jul 9‐13, Washington DC2000.

Google Scholar

Waldemar G, Winblad B, Engedal K, Soininen HS, Verhey FR, Wimo A, Wetterholm AL, Zhang R, Haglund AA, Subbiag P, Donepezil Nordic Study Group. Donepezil benefits patients with either mild of moderate Alzheimer's disease over one year. Neurology2000; Vol. 54, issue Suppl 3:A470.

Google Scholar

Wimo A. Erratum: an economic evaluation of donepezil in mild to moderate alzheimer's disease: results of a 1‐year, double‐blind, randomized trial (dementia and geriatric cognitive disorders (2003) 15 (44‐54)). Dementia and Geriatric Cognitive Disorders 2003;16(2):102.

Google Scholar

Wimo A, Winblad B, Engedal K, Soininen H, Verhey F, Waldemar G, Wetterholm AL, Mastey V, Haglund A, Zhang R, Miceli R, Chin W, Subbiah P, Donepezil Nordic Study Group. An economic evaluation of donepezil in mild to moderate Alzheimer's disease: results of a 1‐year, double‐blind, randomized trial. Dementia and geriatric cognitive disorders 2003;15(1):44‐54.

Wimo A, Winblad B, Mastey V, et al. An economic evaluation of Donepezil in mild to moderate Alzheimers Disease: Results of a one‐year, double‐blind, randomized trial. Proceedings of the World Alzheimer Congress; 2000 Jul 9‐13, Washington DC2000.

Google Scholar

Wimo A, Winblad B, Mastey V, Haglund A, Hertzman P, Miceli R, Jacobson L, Subbiah P. An economic evaluation of donepezil in mild to moderate alzheimer's disease patients: results of a one‐year, double‐blind, randomized trial. Proceedings of the 153rd Annual Meeting of the American Psychiatric Association; 2000 May 13‐18, Chicago, Illionois2000. [MEDLINE: SR‐HANDSRCH]

Google Scholar

Winblad B. Long term therapeutic benefits of acetylcholinesterase inhibitor therapy in patients with alzheimer's disease. Proceedings of the Sixth International Stockholm/Springfield Symposium on Advances in Alzheimer Therapy; 2000 Apr 5‐8, Stockholm2000:164.

Google Scholar

Winblad B, Engedal K, Soininen H, Verhey F, Waldemar G, Wimo A, Wetterholm A, Zhang R, Haglund A, Subbiah P. A 1‐year, randomized, placebo‐controlled study of donepezil in patients with mild to moderate AD. Neurology2001; Vol. 57, issue 3:489‐95.

Google Scholar

Winblad B, Engedal K, Soininen H, Verhey F, Waldemar G, Wimo A, Wetterholm AL, Zhang R, Haglund A, Subbiah P. Donepezil enhances global function and acitivities of daily living compared with placebo in a one‐year, double‐blind trial in patients with mild to moderate alzheimer's disease. Proceedings of the Quality Research in Dementia Conference; 2000 Nov 19‐22, London2000.

Google Scholar

Winblad B, Engedal K, Soininen H, Verhey F, Waldemar G, Wimo A, Wetterholm AL, Zhang R, Haglund A, Subbiah P. Donepezil enhances global function, cognition and activities of daily living compared with placebo in a one‐year, double‐blind trial in patients with mild to moderate Alzheimer's disease. International Psychogeriatrics 1999;11(Supplement 1):138.

Google Scholar

Bullock R, Touchon J, Bergman H, Gambina G, He Y, Rapatz G, Nagel J, Lane R. Rivastigmine and donepezil treatment in moderate to moderately severe Alzheimer's disease over a 2‐year period. Current Medical Research and Opinions 2005;21(8):1317‐1327.

Wilcock GK. Erratum: Efficacy and safety of galantamine in patients with mild to moderate Alzheimer's disease: Multicentre randomised controlled trial (British Medical Journal (December 9)(1445‐1449)). BR‐MED‐J: British‐Medical‐Journal 2001;322(7278):90.

Google Scholar

Wilcock GK. GALANTAMINE ALLEVIATES CAREGIVER BURDEN IN ALZHEIMER'S DISEASE: A 6‐MONTH PLACEBO‐CONTROLLED STUDY. Conference Proceedings World Alzheimer Congress; 9‐13 July, 2000, Washington. 2000.

Google Scholar

Wilcock GK, Lilienfeld S, Gaens E on behalf of the Galantamine International‐1 Study Group. Efficacy and safety of galantamine in patients with mild to moderate Alzheimer's disease: a multicentre randomised controlled trial. British Medical Journal 2000;321:1‐7.

Tariot PN, Solomon PR, Morris JC, Kershaw P, Lilienfeld S, Ding C, Galantamine USA‐10 Study Group. A 5‐month, randomized, placebo‐controlled trial of galamtine in AD. Neurology 2000;54(12):2269‐2276.

Raskind MA, Peskind ER, Wessel T, Yuan W, Galantamine USA‐1 Study Group. Galantamine in AD: A 6‐month randomized placebo‐controlled trial with a 6‐month extension. Neurology 2000;54(12):2261‐2268.

Anand R, Hartman R, Graham S. Effects dof Alzheimer's disease severity on activities of daily living with long‐term rivastigmine treatment. Journal of the American Geriatrics Society 2001;49(4):S151.

Google Scholar

Anand R, Messina J, Veach J, Hartman R. Effects of Rivastigmine in patients with moderately severe Alzheimer's disease. Sixth International Stockholm/Springfield Symposium on Advances in Alzheimer Therapy; April 5‐8, 2000; Stockholm, Sweden. 2000:199.

Google Scholar

Farlow M, Anand R, Messina J, Hartman R. Increased cognitive efficacy of rivastigmine in patients with moderate to severe Alzheimer's disease with co‐existing vascular risk. Sixth International Stockholm/Springfield Symposium on Advances in Alzheimer Therapy; April 5‐8, 2000; Stockholm, Sweden. 2000:206.

Google Scholar

Farlow M, Messina J, Anand R, Hartman R, Veach J. Dose dependent effect of rivastigmine on progression of cognitive deterioration in Alzheimer's disease. In: Sixth International Stockholm/Springfield Symposium on Advances in Alzheimer Therapy; April 5‐8, 2000; Stockholm, Sweden. 2000. 2000:172.

Google Scholar

Hebert M. [Alzheimer disease: efficacy and tolerance of rivastigmine] [Maladie d'Alzheimer: efficacite et tolerance de la rivastigmine]. Presse Medicale 1999;28(32):1757‐8.

Kumar V, Messina J, Hartman R, Anand R. Long‐term cognitive benefits of rivastigmine in Alzheimer's disease patients with vascular risk. Sixth International Stockholm/Springfield Symposium on Advances in Alzheimer Therapy; April 5‐8, 2000; Stockholm, Sweden. 2000:215.

Google Scholar

Lindesay J. An open label one‐year extension of SDZ‐ENA‐713 studies B303, B304 and B305 to prospectively evaluate long‐term safety, tolerability and efficacy of SDZ‐ENA‐713 in out‐patients with probable Alzheimer's disease. National Research Register2000.

Google Scholar

Roesler M, Retz W, Retz Junginger P, Dennler HJ. Effect of two‐year treatment with the cholinesterase inhibitor rivastigmine on behavioural symptoms in Alzheimer's disease. Behavioural‐Neurology 1998;11(4):211‐6.

Rösler M. Efficacy and safety of rivastigmine in patients with Alzheimer's disease: International randomised controlled trial [Erratum]. British Medical Journal2001; Vol. 322, issue 7300:1456.

Google Scholar

Rösler M, Anand R, Cicin‐Sain A, Gauthier S, Agid Y, Dal‐Bianco P, Stähelin HB, Hartman R, Gharabawi M on behalf of the B303 Exelon Study Group. Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomised controlled trial. BMJ 1999;318(7184):633‐638.

Rösler M, Dennler H, Retz W, Gastpar W. A double‐blind placebo controlled study of ENA 713 in Alzheimer's disease (DAT). Pharmacopsychiatry 1997;30:212. [MEDLINE: SR‐HANDSRCH]

Google Scholar

Rösler M, Retz W, Retz Junginger P, Dennler HJ. Effects of two‐year treatment with the cholinesterase inhibitor rivastigmine on behavioural symptoms in Alzheimer's disease. Behavioural‐Neurology 1998;11(4):211‐6.

Vincent S, Andrews C, Lane R. Rivastigmine shows particular efficacy in Alzheimer patients with concomitant hypertension. Proceedings of the 7th International Geneva/Springfield Symposium on Advances in Alzheimer therapy, 2002 Apr 3‐6, Geneva. 2002:253.

Google Scholar

Wilkinson DG. Rivastigmine was effective and safe in Alzheimer disease. ACP Journal Club 1999;131(2):34. [MEDLINE: Cinahl]

Lindesay J. An open label one‐year extension of SDZ‐ENA‐713 studies B303, B304 and B305 to prospectively evaluate long‐term safety, tolerability and efficacy of SDZ‐ENA‐713 in out‐patients with probable Alzheimer's disease. National Research Register2000.

Google Scholar

Novartis. No title. Unpublished. Data provided by Novartis No year.

Novartis Pharmaceuticals. ADENA Programme. Unpublished Data1998.

Google Scholar

Novartis. No title. Unpublished. Data provided by Novartis No year.

Novartis Pharmaceuticals. ADENA Programme. Unpublished Data1998.

Google Scholar

Corey‐Bloom J, Anand R and Veach J for ENA 713 B352 Study Group. A randomized trial evaluating the efficacy and safety of ENA 713 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe Alzheimer's disease. Int J Ger Psychopharmacology 1998;1:55‐65.

Google Scholar

Doraiswamy M. The effects of rivastigmine on the alzheimer's disease assessment scale‐cognitive subscale items scores of patients with alzheimer's disease. Health in aging the challenge and promise of new decade. Proceedings of the annual scientific meeting of the American geriatrics society and the American federation for aging research; 2000 May 17‐21, Nashville. 2000:173.

Google Scholar

Doraiswamy PM, Anand R, Hartman R. Cognitive effects of rivastigmine in patients with mild to moderate alzheimer's disease compared to those with moderately‐severe to severe AD. Clinical Neuropschological Assessment 2000;1(6):12.

Google Scholar

Doraiswamy PM, Anand R, Hartman R. Long term cognitive effects in Alzheimer's disease patients stratified by vascular risk score and treated for 1 year with rivastigmine. Clinical Neuropschological Assessment 2000;1(6):14.

Google Scholar

Farlow M, Hake A, Messina J, Veach J, Anand R. The response of patients with Alzheimer's disease to rivastigmine treatment is predicted by the rate of disease progression. Neurology2000; Vol. 54, issue Suppl 3:A469.

Google Scholar

Farlow M, Messina J, Anand R. Long term cognitive benefits associated with the use of rivastigmine in the treatment of Alzheimer's disease results following two years of treatment. Proceedings of the Annual Scientific Meeting of the American Geriatric Society and the American Federation for Aging Research; 2000 May 17‐21, Nashville. 2000:172.

Google Scholar

Farlow MR, Hake A, Messina J, Hartman R, Veach J, Anand R. Response of patients with Alzheimer disease to rivastigmine treatment is predicted by the rate of disease progression. Archives of Neurology 2001;58(3):417‐22.

Ferris S. Improving day to day functioning in patients with AD. Proceedings of the Ninth Congress of the International Psychogeriatric Association; 1999 Aug 15‐20, Vancouver. 1999:77.

Google Scholar

Krishnan KR, Dorasiswamy PM, Messina J, Veach J, ENA 713 B352 Study Group. Rivastigmine slows stage specific global deterioration in Alzheimer's disease. Journal of the American Geriatrics Society 1999;47:S3.

Google Scholar

Kumar V, Anand R, Messina J, Hartman R, Veach J. An efficacy and safety analysis of Exelon in Alzheimer's disease patients with concurrent vascular risk factors. European Journal of Neurology 2000;7(2):159‐69.

Veach KR, Doraiswamy PM. Rivastigmine slows stage‐specific global deterioration in Alzheimer's disease. Proceedings of the 152nd Annual Meeting of the American Psychiatric Association; 1999 May 15‐20, Washington DC. 1999. [MEDLINE: SR‐HANDSRCH]

Google Scholar

Referencias de los estudios excluidos de esta revisión

Ir a:

estudios incluidos
otras referencias

AD2000 Collaborative Group. Long‐term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double‐blind trial. Lancet 2004;363:2105‐15.

Bentham P, Gray R, Hill R, Sellwood E, Courtney C. Twelve week respone to cholinesterase inhibitors dose not predict future benefit the AD2000 trial experiance. The 8th conference on Alzheimer's disease and related disorders, July 20‐25, 2002, Stockholm, Sweden. 2002:337.

Google Scholar

Lendon CL. Determination of respones to anticholinesterase therapy in the treatment of Alzheimer's disaese. The 8th conference on Alzheimer's disease and related disorders, July 20‐25, 2002, Stockholm, Sweden2002:1287.

Google Scholar

Lendon CL. Determination of responses to anticholinesterase therapy in the treatment of Alzheimer's disease. Proceedings of the 8th International Conference on Alzheimer's Disease and Related Disorders; 2002 July 20‐25, Stockholm, Sweden: Abstract No 1287. 2002.

Google Scholar

Roberts N. A reliable assessment of the efficacy and safety of donepezil and aspirin in Alzheimer's disease (AD2000). National Research Register2001.

Google Scholar

Schneider LS. AD2000: donepezil in Alzheimer's disease. Lancet2004; Vol. 363, issue 9427:2100‐1.

Google Scholar

Waghray S. AD2000 A reliable assessment of the efficacy and safety of donepezil and aspirin in Alzheimer's disease. National Research Register2000. [MEDLINE: http://www.doh.gov.uk/nrr.htm]

Google Scholar

Tune L, Tiseo P, Hoffman J, Perdomo C, Votaw J, Rogers S, Friedhoff L. PET in AD: Donepezil HCl (E2020) maintains functional brain activity in patients with Alzheimer's disease: results of a 24‐week study. Proceedings of the 14th Annual Meeting of the American Association for Geriatric Psychiatry; 2001 Feb 23‐26 San Francisco. 2001.

Google Scholar

Tune L, Tiseo PJ, Ieni J, Perdomo C, Pratt RD, Votaw JR, Jewart RD, Hoffman JM. Donepezil HCl (E2020) maintains functional brain activity in patients with Alzheimer disease: results of a 24‐week, double‐blind, placebo‐controlled study. American Journal of Geriatric Psychiatry 2003;11(2):169‐177.

Tune LE, Tiseo PJ, Hoffman JM, Perdomo CA, Votow JR, Rogers SL, Friedhoff LT. Functional Brain Activity in Alzheimer's Disease. Proceedings of the 151st Annual Meeting of the American Psychiatric Association; 1998 May 30‐ Jun 4, Toronto. 1998:NR345. [MEDLINE: SR‐HANDSRCH]

Google Scholar

Anon. No title. Eisai Inc..

Jones RW, Soininen H, Hager K, Aarsland D, Passmore P, The DONGAL Study Group, Murthy A, Zhang R, Bahra R. A multinational, randomised, 12‐week study comparing the effects of donepezil and galantamine in patients with mild to moderate Alzheimer's disease. International Journal of Geriatric Psychiatry 2004;19:58‐67.

Wilcock G, Howe I, Coles H, Lilienfeld S, Truyen L, Young Z, Bullock R, and members of the GAL‐GBR‐2 Study Group. A long‐term comparison of galantamine and donepezil in the treatment of Alzheimer's disease. Drugs Aging 2003;20(10):777‐789.

Bullock R, Passmore F, Potocnik F, Hock C. The tolerability, ease of use and efficacy of donepezil and rivastigmine in alzeimer's disease patients: a 12‐week, multinational, comparative study. Journal of the American Geriatrics Society2001; Vol. 49, issue 4:S19.

Google Scholar

Bullock R, Wilkinson DG, Passmore P, Hopker SW, Smith R, Potocnik FC, Maud CM, Hock C. Caregiver and physician determination of satisfaction with and ease of use of donepezil and rivastigamine treatment in alzheimer's disease patients. Proceedings of the 17th Alzheimer's Disease International Conference; 2001 Oct 25‐27, Christchurch, New Zealand2001:39.

Google Scholar

Böttcher‐Buhler E. [Well tolerated, effective and inexpensive therapy of Alzheimer's dementia with donepezil] [Therapie der Alzheimer‐Demenz mit Donepezil: gut vertraglich, wirksam und kostengunstig]. Neurologie und Rehabilitation2000; Vol. 6, issue 6:332‐3.

Google Scholar

Potocnik FC, Smith R, Passmore P, Hock C, Wilkinson D, Maud CM, Hopker S. Tolerability, ease of use, and efficacy of donepezil and rivastigmine in alzheimer's disease patients. Proceedings of the Annual Meeting of the American Psychiatric Association; 2001 May 5‐10; New Orleans2001.

Google Scholar

Wilkinson D, Passmore P, Potocnik F, Maud C, Hock C. Donepezil compared to rivastigmine in Alzheimer's disease: similar efficacy but better tolerability and physician and caregiver satisfaction in a multinational randomized trial. Proceedings of the 14th Annual Meeting of the American Association for Geriatric Psychiatry; 2001 Feb 23‐26, San Francisco2001.

Google Scholar

Wilkinson DG, Passmore AP, Bullock R, Hopker SW, Smith R, Potocnik FCV, Maud CM, Engelbrecht I, Hock C, Ieni JR, Bahra RS. A multinational, randomised, 12‐week, comparative study of donepezil and rivastigmine in patients with mild to moderate Alzheimer's disease. International Journal of Clinical Practice 2002;56(6):441‐446.

Fuschillo C, La Pia S, Campana F, Pinto A, De Simone L. Cognitive deficits in alzheimer's disease: treatment with acetylcholinesterase inhibitor agents. Archives of Gerontology and Geriatrics 2001;33(Suppl 1):151‐8.

Brodaty H, Corey‐Bloom J, Potocnik FCV, Truyen L, Gold M, Damaraju CRV. Galantamine Prolonged‐Release Formulation in the Treatment of Mild to Moderate Alzheimer's Disease. Dement Geriatr Cogn Disord 2005;20(2‐3):120‐132.

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;359:1283‐1290..

Erkinjuntti T, Kurz A, Gauthier S, Bullock R, Lilienfeld S, Damaraju CV. The safety and efficacy of Galantamine in the treatment of vascular and mixed dementia (Double‐blind part only). (GAL‐INT‐6). Johnson and Johnson Pharmaceutical Research & Development.January 2004.

Google Scholar

Krishnan KR, Charles HC, Doraiswamy PM, Mintzer J, Weisler R, Yu X, Perdomo C, Ieni JR, Rogers S. Randomized, placebo‐controlled trial of the effects of donepezil on neuronal markers and hippocampal volumes in Alzheimer's disease. American journal of psychiatry, The 2003;160(11):2003‐11.

Mega M, Dinov I, Manese M, Felix J, O'Connor S, Toga A, Cummings J. Cerebral metabolic activation with cholinesterase inhibitor therapy in Alzheimer's disease. The 8th conference on Alzheimer's disease and related disorders, July 20‐25, 2002, Stockholm, Sweden2002:430.

Google Scholar

Rozzini L, Bargnani C, Bosio A, Chia F, Franzani S, Leonardi R, Ranzenigo A, Rozzini R, Saviotti FM, Turla M, Trabucchi m, Ghianda D, Borroni B, Chilovi BV, Padovani A. Acetylcholinesterase inhibitors are effective in real world patients with mild to moderate Alzheimer disease evidence from a large population treated with rivastigmine or donepezil. The 8th conference on Alzheimer's disease and related disorders, July 20‐25, 2002, Stockholm, Sweden. 2002:329.

Google Scholar

Rozzini L, Bargnani C, Bosio A, Chia F, Franzoni S, Leonardi R, Ranzenigo A, Rozzini R, Saviotti FM, Turla M, Trabucchi M, Vicini B, Borroni B, Padovani A. Comparison of efficacy and safety of rivastigmine and donepezil in patients with mild to moderate alzheimer disease: results from a multicentre randomised trial.. The 8th conference on Alzheimer's disease and related disorders, July 20‐25, 2002, Stockholm, Sweden. 2002:240.

Google Scholar

Shua‐Haim J, Smith J, Potel S. A head to study of donepezitl aricept rivastigmine exlon and galantamine reminyl for the treatment of Alzheimer's disease safety tolerability clinical and caregiver impression after 4‐5 months of trratment a prospective study. The 8th conference on Alzheimer's disease and related disorders, July 20‐25, 2002, Stockholm, Sweden2002:286.

Google Scholar

Ebell M. Does donepezil help patients with moderate Alzheimer's dementia preserve their ability to function independently?. Evidence Based Practice2002.

Google Scholar

Mohs R, Doody R, Morris J, Ieni J, Perdomo C, Pratt R, Rogers S. Donepezil preserves activities of daily living in alzheimer's disease patients: results from a one‐year placebo‐controlled functional survival study. Neurology2000; Vol. 54, issue Suppl 3:A415.

Google Scholar

Mohs R, Doody R, Morris J, Ieni J, Rogers S, Perdomo C, Pratt R. Donepezil preserves functional status and improves cognition in alzheimer's disease patients: results from a 1‐year propective placebo‐controlled study. Journal of the American Geriatrics Society2000; Vol. 48, issue 8:S46.

Google Scholar

Mohs R, Doody R, Morris J, Ieni JR, Rogers SL, Perdomo CA, Pratt RD. Donepezil preserves functional status in Alzheimer's disease patients: results from a 1‐year prospective placebo‐controlled attrition study. Journal of the European College of Neuropsychopharmacology 1999;9(Suppl 5):S328.

Mohs R, Doody R, Morris J, Ieni JR, Rogers SL, Perdomo CA, Pratt RD. Donepezil preserves functional status in Alzheimer's disease patients: results from a 1‐year prospective placebo‐controlled study. Proceedings of the Quality Research in Dementia Conference; 2000 Nov 19‐22, London. 2000.

Google Scholar

Mohs RC, Doody RS, Morris JC, Ieni JR, Rogers SL, Perdomo C, Pratt RD, 312 Study Group. A 1‐year, placebo‐controlled preservation of function survival study of donepezil in AD patients [Erratum]. Neurology2001; Vol. 57, issue 10:1942. [MEDLINE: http://www.lww.com]

Google Scholar

Mohs RC, Doody RS, Morris JC, Ieni JR, Rogers SL, Perdomo CA, Pratt RD. A 1‐year, placebo‐controlled preservation of function survival study of donepezil in AD patients. Neurology2001; Vol. 57, issue 3:481‐8.

Google Scholar

Mohs RC, Doody RS, Morris JC, Leni JR, Rogers SL, Perdomo CA, Pratt RD. Donepezil preserves functional status in Alzheimer's disease. Proceedings of the 153rd Annual Meeting of the American Psychiatric Association; 2000 May 13‐18, Chicago, Illionois. 2000. [MEDLINE: SR‐HANDSRCH]

Google Scholar

Pratt R, Mohs R, Doody R, Morris J, Rogers S, Ieni J, Perdomo C. Donepezil preserves functional status in Alzheimer's disease patients results from a 1‐year prospective placebo controlled functional study. Proceedings of the 6th International Stockholm/Springfield Symposium on Advances in Alzheimer Therapy; April 5‐8, 2000; Stockholm, Sweden2000b:178.

Google Scholar

Tsolaki M, Gerothanassis D, Aristotle CP. Efficacy and safety of cholinesterase inhibitors a longitudinal comparative study between donepezil and rivastigmine. The 8th conference on Alzheimer's disease and related disorders, July 20‐25, 2002, Stockholm, Sweden2002:2038.

Google Scholar

Wang Y, Chen Q, Zhang Z, et al. The treatment by using rivastigmine for patients with alzheimer disease: results of a multicenter, randomized, open‐labeled, controlled clinical trial. Chinese Journal of Neurology 2001;34(4):210‐3.

Google Scholar

Werber EA, Klein C, Rabey MJ. Evaluation of cholinergic treatment in demented by p300 evoked related potentials. The 8th conference on Alzheimer's disease and related disorders, July 20‐25, 2002, Stockholm, Sweden2002:442.

Google Scholar

Referencias adicionales

Ir a:

estudios incluidos
estudios excluidos

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 3rd Edition. Washington DC: APA, 1987:American Psychiatric Association.

Birks JS, Harvey R. Donepezil for dementia due to Alzheimer's disease (Cochrane Review). The Cochrane Library 2005, Issue 3.

Google Scholar

Birks J, Grimley Evans J, iakovidou V, Tsolaki M. Rivastigmine for Alzheimer's disease (Cochrane Review). The Cochrane Library 2005, Issue 3.

Google Scholar

Bucks RS, Ashworth DL, Wilcock GK, Siegfried K. Assessment of activities of daily living in dementia: development of the Bristol activities of daily living scale. Age Ageing 1996;25:113‐120.

Cummings JL, Mega M, Gray K, Rosenburg‐Thompson S, Carusi DA, Gornbein J. The neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia. Neurology 1994;44:2308‐2313.

DeJong R, Osterlund OW, Roy GW. Measurement of quality‐of‐life changes in patients with Alzheimer's disease. Clin Ther 1989;11(4):545‐554.

Erkinjuntti T, Skoog I, Lane R, Andrews C. Rivastigmine in patients with Alzheimer's disease and concurrent hypertension. International Journal of Clinical Practice 2002;56(10):791‐796.

Folstein NF, 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.

Galasko D, Bennett D, Sano M, et al. An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord 1997;11(Suppl 2):533‐539.

Google Scholar

Gottfries CG, Brane G, Gullberg B, Steen G. A new rating scale for dementia syndromes. Arch Gerontol Geriatr 1982;1:311‐330.

Gélinas I, Gauthier L, McIntyre M, et al. Development of a functional measure for persons with Alzheimer's disease: the Disability Assessment for Dementia. American Journal of Occupational Therapy 1999;53:471‐481.

Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327:557‐560.

Kumar V, Anand R, Messina J, Hartman R, Veach J. An efficacy and safety analysis of Exelon in Alzheimer's disease patients with concurrent vascular risk factors. European Journal of Neurology 2000;7(2):159‐169.

Loy C, Schneider L. Galantamine for Alzheimer's disease (Cochrane Review). The Cochrane Library 2005, Issue 3.

Google Scholar

McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical Diagnosis of Alzheimer’s Disease: Report of the NINCDS‐ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984;4:939‐944.

Olin J, Schneider L. Galantamine for Alzheimer's disease (Cochrane Library). The Cochrane Library 2005, Issue 3.

Google Scholar

Panisset M, Roudier M, Saxton J, Boller F. Severe impairment battery. A neurological test for severely demented patients. Archives of Neurology 1994;51:41‐45.

Reisberg B, Ferris SH, De Leon MJ, Crook T. the global deterioration sclae for assessment of primary degenerative dementia. Am J Psychiatry 1982;139:1136‐1139.

Rosen WG, Mohs RC, Davis K. A new rating scale for Alzheimer's disease. Am J Psychiatry 1984;141:1356‐1364.

Schneider LS, Olin JT, Doody RS, et al. Validity and reliability of the Alzheimer's Disease Cooperative Study ‐ Clinical Global Impression of Change. AD Assoc Dis 1997;11(suppl 2):S22‐32.

Wimo A, Wetterholm AL, Mastey V, Winblad B. Evaluation of the healthcare resource utilization and caregiver time in anti‐dementia drug trials. In: Wimo A, Jönsson B, Karlsson G, Winblad B editor(s). Health Economics in Dementia. Chichester: Wiley, 1998:465‐477.

Google Scholar

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Ir a:

estudios excluidos

DON vs RIV/Bullock

Methods	104 week, randomized, double‐blind, parallel group
Participants	Country: Australia, Canada, France, Germany, Italy, Spain, UK 94 centres, 998 participants with mild to moderate probable Alzheimer's disease (DSM‐IV and NINCDS‐ADRDA criteria), mean MMSE 15.1(3.0), mean age 75.9 (6.7) Inclusion criteria: MMSE 10‐20 Exclusion criteria: other neurodegenerative disease, any advanced, unstable, severe disease, major depressive episode, seizure disorder, peptic ulceration, acute or severe asthma or cardiovascular disease, cerebrovascular disease, certain other medication
Interventions	1. donepezil (10mg/day) 2. rivastigmine (maximum 12mg/day in two doses)
Outcomes	SIB GDS ADCS‐ADL MMSE NPI
Notes

DON‐302

Methods	24‐week, randomized, double‐blind, parallel‐group, placebo‐controlled study ‐ a computer randomization schedule was used
Participants	Country: USA Multi‐centre (20 sites) 473 participants, aged 51‐94 years, 180 men and 293 women. Selection criteria: Eligible patients had a diagnosis of uncomplicated AD, according to the NINCDS‐ADRDA criteria and DSM‐III‐R categories 290.00 and 290.10, with no clinical or laboratory evidence of a cause other than AD for their dementia. MMSE between 10 and 26, and CDR=1 (mild dementia) or 2 (moderate dementia). All participants had a reliable caregiver. Exclusion criteria: evidence of insulin dependent diabetes mellitus or other endocrine disorder. Asthma, obstructive pulmonary disease or clinically significant uncontrolled gastrointestinal hepatic or cardiovascular diseases. Patients known to be hypersensitive to ChE inhibitors or who had taken tacrine or other investigational medicines within 1 month of baseline were excluded. Concomitant medications such as anticholinergics, anticonvulsants, antidepressants and antipsychotics were not allowed. Drugs with CNS activity were prohibited or partially restricted.
Interventions	1. placebo 2. donepezil 5mg/day 3. donepezil 10mg/day
Outcomes	Primary: ADAS‐Cog CIBIC plus (including caregiver information) secondary: MMSE QoL (patient rated) CDR‐SB (Clinical dementia scale, sum of boxes)
Notes	The group on 10mg/d of donepezil was on a blinded forced titration scheme of 5mg/d for week 1, and 10mg/d for the remainder of the study. Measures of clinical outcome were assessed at baseline and at 6‐week intervals

DON‐304

Methods	24‐week double‐blind, parallel‐group, placebo‐controlled, randomized study ‐ the randomization schedule was computer‐generated
Participants	Country: Europe Multi‐centre 818 participants, 348 men and 470 women, with mild to moderately severe AD, mean age 71.7 (8.3), mean MMSE 20.2 (5.0) Country: Europe, South Africa, New Zealand, Australia and Canada Multiple centre (82 sites) Selection criteria: Eligible patients had a diagnosis of probable AD, according to the NINCDS‐ADRDA criteria and DSM‐III‐R categories 290.00 and 290.10, with no clinical or laboratory evidence of a cause other than AD for their dementia. MMSE between 10 and 26, and CDR=1 (mild dementia) or 2 (moderate dementia). All participants had a reliable caregiver. CT or MRI within 6 months of entry. Exclusion criteria: evidence of insulin dependent diabetes mellitus or other endocrine disorder. Asthma, obstructive pulmonary disease or clinically significant uncontrolled gastrointestinal hepatic or cardiovascular diseases. Patients known to be hypersensitive to ChE inhibitors or who had taken tacrine or other investigational medicines within 1 month of baseline were excluded. Concomitant medications such as anticholinergics, anticonvulsants, antidepressants and antipsychotics were not allowed. Drugs with CNS activity were prohibited or partially restricted.
Interventions	1. placebo 2. donepezil 5 mg/day 3. donepezil 10 mg/day
Outcomes	ADAS‐Cog CIBIC‐Plus CDR‐SB (CDR sum of boxes) QoL IDDD (functional evaluations)
Notes	Patients in the 10mg/day group received 5mg/day for the first week of treatment. 6‐week placebo washout phase followed the double‐blind phase. The group on 10mg/d of donepezil was on a blinded forced titration scheme of 5mg/d for week 1, and 10mg/d for the remainder of the study. Measures of clinical outcome were assessed at baseline and at 6‐week intervals

DON‐311

Methods	24‐week double‐blind, parallel group, placebo controlled, randomized study
Participants	Country: USA Multi‐centre (27 sites) study with 208 participants, 37 men and 171 women, with possible or probable AD, or AD with cerebrovascular disease (but not vascular dementia) Inclusion criteria: MMSE between 5 and 26 inclusive, residence in nursing home, at least one NPI symptom reported at a frequency of at least several times per week. Exclusion: most concomitant medications were allowed except those with significant cholinergic or anticholinergic effects
Interventions	1. placebo 2. donepezil 10 mg/day
Outcomes	NPI‐NH MMSE CDR‐SB
Notes	The group on donepezil took 5 mg/d for the first 4 weeks, followed by 10 mg/d for 20 weeks.

DON‐402

Methods	24‐week double‐blind, parallel‐group, placebo‐controlled, randomized study
Participants	Country: USA Multi‐centre (17 sites) 153 participants, 71 men and 82 women, with probable AD diagnosed within the last year (DSM‐IV and NINCDS‐ADRDA), mean age 74.0 years, mean MMSE=24.1. Inclusion criteria: modified Hachinski <=4, CDR 0.5 or 1.0, MMSE 21‐26, only mild impairment of ADL Exclusion criteria: if memory impairment was due to stroke or Parkinson's disease, previous treatment with cholinesterase inhibitor
Interventions	1. placebo 2. donepezil 5mg/day for 6 weeks followed by forced escation to 10mg/day thereafter
Outcomes	mADAS‐Cog MMSE CDR‐sum of boxes CMBT Apathy scale patient rated global assessment
Notes	patients unable to tolerate 10mg/day were dropped from the study

DON‐Feldman

Methods	24‐week double‐blind, parallel‐group, placebo‐controlled, randomized study ‐ the randomization schedule was computer‐generated
Participants	Country: Canada, Australia, France Multi‐centre (32 sites) 292 participants, aged 51‐94 years, 115 men and 177 women. Selection criteria: Eligible patients had a diagnosis of probable or possible AD, of moderate or severe severity, according to the NINCDS‐ADRDA criteria with no clinical or laboratory evidence of a cause other than AD for their dementia. MMSE between 5 and 17. All participants had a reliable caregiver. Exclusion criteria: delirium, depression or other illness that may interfere with the study. Other neurologic or psychiatric diagnosis. History of drug or alcohol misuse. Hypersensitivity to AChE inhibitors. Clinically obstructive airway disease, asthma, haematologic or oncologic disorder within last 2 years. B12 or folate deficiency, active gastrointestinal, renal, hepatic, endocrine or cardiovascular system disease. Most concomitant medications were allowed except those with notable cholinomimetic or anticholinergic effects.
Interventions	1. placebo 2. donepezil 10 mg/day
Outcomes	CIBIC plus MMSE SIB DAD IADL PSMS NPI FRS CSS SF‐36 CAUST
Notes	The group on donepezil took 5 mg/d for the first 4 weeks, followed by 10 mg/d for 20 weeks. The dose could be reduced to 5mg/day at any point if necessary

DON‐Nordic

Methods	52‐week, double‐blind, parallel‐group, placebo‐controlled, randomized study
Participants	Country: Northern Europe multi‐centre (28 sites), 286 participants, 102 men and 184 women, age range 49‐88 years, with mild to moderate possible or probable AD. Selection criteria: Diagnosis of AD with DSM‐IV and NINCDS‐ADRDA criteria, with 9< MMSE <27
Interventions	1. placebo 2. donepezil 10 mg/day
Outcomes	GBS MMSE PDS GDS IADL PSMS RUD
Notes	The group on donepezil received 5mg/d for 28 days initially, and then 10mg/d according to the clinician's judgement for 1 year.

GAL‐INT‐1 Wilcock

Methods	Randomized Double‐blind Parallel‐group Placebo‐controlled, with 4‐week placebo run‐in Duration: 26 weeks
Participants	Country: 8 European No. of Centers: 86 Diagnosis: At least 6 month history of progressive cognitive decline, Senile Dementia Alzheimer's Type defined by: NINCDS‐ADRDA. Inclusion: MMSE score of 11 to 24, ADAS‐cog score > 11; CT or MRI < 12 months previously with no evidence of multi‐infarct dementia or active cerebrovascular disease; responsible caregiver; discontinued from antidementia medications; discontinued where possible form anticholinergic or cholinomimetic agents. Exclusion: Past cholinesterase inhibitor use; uncontrolled hypertension, heart failure, type II diabetes mellitus, hypothyroidism; other neurodegenerative disorders; cardiovascular disease that would affect completion of the trial; clinically significant psychiatric, hepatic, renal, pulmonary, metabolic, endocrine conditions; urinary outflow obstruction; active peptic ulcer; history of epilepsy, significant substance abuse. Total No. of patients: 653 Sex: Not stated. Age: [placebo 72.7 (7.6)] [galantamine 24mg 71.9 (8.3)] [galantamine 32mg 72,1 (8.6)]
Interventions	Route: oral Treatment: galantamine 12mg b.i.d. galantamine 16mg b.i.d. Treatment commenced at 4mg b.i.d. and was progressively increased weekly by 8mg/d to assigned maximum dose. Control: Placebo b.i.d.
Outcomes	ADAS‐cog ADCS‐CGIC Expanded ADAS‐cog DAD (Disability Assessment for Dementia)
Notes	No. excluded after randomization: 128 No. not included in analysis: 128

GAL‐USA‐1 Raskind

Methods	Randomized Double‐blind Parallel‐group Placebo‐controlled, with 4‐week placebo run‐in Duration: 26 weeks/ 6 months
Participants	Country: USA No. of Centers: 33 Diagnosis: Senile Dementia Alzheimer's Type defined by: NINCDS‐ADRDA. Inclusion: MMSE score of 11 to 24 inclusive, ADAS‐cog score > 11; responsible caregiver; free for 30 days of medications indicated for dementia (3 months for cholinesterase inhibitors); written informed consent by patient or appropriate representative. Exclusion: Uncontrolled hypertension, heart failure, type II diabetes mellitus, hypothyroidism; other neurodegenerative disorders; cardiovascular disease that would affect completion of the trial; clinically significant psychiatric, hepatic, renal, pulmonary, metabolic, endocrine conditions; urinary outflow obstruction; active peptic ulcer; history of epilepsy, significant substance abuse. Total No. of patients: 636 Sex: 242 males. Age: 70.3 +/‐ 1.6 to 71.1 +/‐ 1.5 (broken down by treatment group)
Interventions	Route: oral Treatment: galantamine 12mg b.i.d. galantamine 16mg b.i.d. Treatment commenced at 4mg b.i.d. and was increased weekly by 8mg/d to assigned maximum dose. Control: Placebo b.i.d.
Outcomes	ADAS‐cog ADCS‐CGIC DAD (Disability Assessment for Dementia)
Notes	No. excluded after randomization: 198 No. not included in observed case analysis: 198

GAL‐USA‐10 Tariot

Methods	Randomized Double‐blind Parallel‐group Placebo‐controlled, with 4‐week placebo run in Duration: 5 months
Participants	Country: United States No. of Centers: Unstated Diagnosis: At least 6 month history of progressive cognitive decline, Senile Dementia Alzheimer's Type defined by: NINCDS‐ADRDA. Inclusion: MMSE score of 10 to 22, ADAS‐cog score > 17; CT or MRI < 12 months previously with no evidence of multi‐infarct dementia or active cerebrovascular disease; responsible caregiver; free for 30 days of medications indicated for dementia; free for 60 days for cholinomimetic agents. Exclusion: Uncontrolled hypertension, heart failure, type II diabetes mellitus, hypothyroidism; other neurodegenerative disorders; cardiovascular disease that would affect completion of the trial; clinically significant psychiatric, hepatic, renal, pulmonary, metabolic, endocrine conditions; urinary outflow obstruction; active peptic ulcer; history of epilepsy, significant substance abuse. Total No. of patients: 978 Sex: 353 males Age: 76.0 +/‐ 0.6 to 77.7 +/‐ 0.4
Interventions	Route: oral Treatment: galantamine 4mg b.i.d. galantamine 8mg b.i.d. galantamine 12mg b.i.d. Treatment commenced at 8mg/d and was increased 8mg/d every 4 weeks until the target dose had been reached. Control: Placebo b.i.d.
Outcomes	ADAS‐cog ADCS‐CGIC ADCS‐ADL (Alzheimer's Disease Cooperative Study Activities of Daily Living), NPI (Neuropsychiatric Inventory)
Notes	No. excluded after randomization: 199 No. not included in observed cases analysis: 199

RIV‐B303

Methods	26 week double‐blind randomized: method described placebo‐controlled parallel‐group
Participants	Country: Europe and North America 45 centres 725 participants (428 female, 297 male) age range 45‐95 years mean age=72 years Inclusion: DSM‐IV, NINCDS‐ADRDA criteria for probable AD. MMSE 10‐26 inclusive 50‐85 years old (outside this range with approval of medical expert), most concomitant disease, most medications Exclusion: severe and unstable cardiac disease, severe obstructive pulmonary disease, other life threateneing conditions (eg rapidly progressing malignancies), , anticholinergic drugs, acetylcholine precursor health food supplements, memory enhancers, insulin, psychotropic drugs (apart from occasional use of chloral hydrate for agitation or insomnia)
Interventions	1.rivastigmine 1‐4mg/day divided into 2 doses 2.rivastigmine 6‐12mg/day divided into 2 doses 3.placebo doses increased weekly insteps of 1.5mg/day during weeks 1‐12, but had to be within target range by week 7
Outcomes	ADAS‐Cog CIBIC‐plus PDS GDS CAS MMSE
Notes	Main hypothesis: to assess the effects of rivastigmine on the core domains of AD Assessments: baseline, 12,18,26 weeks

RIV‐B304

Methods	26 week double‐blind randomized placebo‐controlled parallel‐group
Participants	Country: Australia, Canada, Italy, South Africa, UK 38 centres 678 participants Inclusion: DSM‐IV, NINCDS‐ADRDA criteria for probable AD. MMSE range 10‐26 inclusive Exclusion: significant illness, severe chronic pulmonary disease, psychiatric or neurological disorder, severe cardiovascular problems, clinically significant lab tests, including those indicative of impaired renal or liver function
Interventions	1.rivastigmine 2‐12 mg/day divided into 2 doses 2.rivastigmine 2‐12 mg/day divided into 3 doses 3.placebo titration to highest tolerated dose during weeks 1 and 2. During weeks 3‐26 dose variation allowed
Outcomes	ADAS‐Cog CIBIC‐plus PDS GDS CAS MMSE
Notes	Main hypothesis: to evaluate the efficacy and safety of individual highest well tolerated doses (range 2‐12 mg/d) of rivastigmine bid or tid for 26 weeks compared to placebo, in the therapy of patients with probable AD

RIV‐B351

Methods	26 week double‐blind randomized placebo‐controlled parallel‐group
Participants	Country: USA 14 centres 702 participants (393 female, 309 male) age range 45‐89 years, mean =74.5 years Inclusion: DSM‐IV, NINCDS‐ADRDA criteria for probable AD. MMSE range 10‐26 inclusive head computed tomography or magnetic resonance imaging scan consistent with AD within 12 months , most concomitant disease, most medications Exclusion: severe and unstable medical illnesses, anticholinergic drugs, acetylcholine precursor health food supplements, memory enhancers, insulin, psychotropic drugs (apart from occasional use of chloral hydrate for agitation or insomnia)
Interventions	1.rivastigmine:3 mg/day divided into 2 doses 2.rivastigmine:6 mg/day divided into 2 doses 3.rivastigmine:9 mg/day divided into 2 doses 4.placebo titration during weeks 1‐12 to the fixed dose, no dose reductions allowed
Outcomes	ADAS‐Cog CIBIC‐plus PDS GDS CAS MMSE CAS
Notes	Main hypothesis: to evaluate the efficacy and safety of 3 fixed doses of rivastigmine (3,6,9 mg/d) and placebo for 26 weeks of treatment, and dose/efficacy and dose/safety relationships in patients with probable mild to moderate AD Assessments: baseline, 12,18,26 weeks

RIV‐B352

Methods	26 week double‐blind randomized:method described placebo‐controlled parallel‐group
Participants	Country: USA 22 centres 699 participants (426 female, 273 male) age range 45‐89 years, mean =74.5 years inclusion: DSM‐IV, NINCDS‐ADRDA criteria for probable AD. MMSE range 10‐26 inclusive head computed tomography or magnetic resonance imaging scan consistent with AD within 12 months, most concomitant disease, most medications exclusion: severe and unstable medical illnesses, anticholinergic drugs, acetylcholine precursor health food supplements, memory enhancers, insulin, psychotropic drugs (apart from occasional use of chloral hydrate for agitation or insomnia)
Interventions	1.rivastigmine 1‐4mg/day divided into 2 doses 2.rivastigmine 6‐12mg/day divided into 2 doses 3.placebo titration phase week 0‐7, flexible phase weeks 8‐26, dose bid with food
Outcomes	ADAS‐Cog CIBIC‐plus PDS GDS CAS MMSE
Notes	primary hypothesis:to evaluate efficacy and safety of rivastigmine assessments: baseline, 12,18,26 weeks open label extension

Characteristics of excluded studies [ordered by study ID]

Ir a:

estudios incluidos

Study	Reason for exclusion
AD2000	Randomized, placebo controlled, double blind trial of donepezil. Results for the 5 and 10 mg/day groups were not reported separately. Complex design and high numbers of dropouts made analysis and interpretation difficult.
DON vs GAL/Jones	Single‐blinded study of 12 weeks only.
DON vs GAL/Wilcock	Single blinded study.
DON vs RIV/Wilkinson	Single‐blinded study of 12 weeks only.
Donepezil‐203	Randomized, placebo controlled, double blind trial of donepezil. Designed to evaluate effect on brain glucose metabolism and no data to contribute to this review.
Donepezil‐204	Randomized, placebo controlled, double blind trial of donepezil. Designed to evaluate effect on brain glucose metabolism and no data to contribute to this review.
Fuschillo 2001	Randomized study of donepezil 5 mg/day compared with rivastigmine 6‐9 mg/day for AD. Not blinded.
GAL‐INT‐10	Randomized, double‐blind, placebo controlled study of galantamine. Dose available could be as high as 24 mg/day, but the mean dose was 17mg/day, which was too low for this review.
GAL‐INT‐6Erkinjuntti	Diagnosis of the included patients was not for simply AD. Randomized, placebo controlled, double blind trial of donepezil, for AD with cerebrovascular disease
Krishnan 2003	Randomized, placebo controlled, double blind trial of donepezil. Designed to evaluate effect on N‐acetylasparate concentration and hippocampal volume and no data to contribute to this review.
Mega 2002	Non‐randomized study of donepezil, metrifonate or galantamine. Outcome is response to cerebral metabolic activation.
Rozzini 2002	Donepezil compared with rivastigmine in a non‐randomzied study.
Shua‐Haim 2002b	Donepezil compared with rivastigmine compared with galantamine. No mention of randomization
Study 312/314	Randomized, placebo controlled, double blind trial of donepezil. Designed to evaluate preservation of function. Patients left the trial when function declined to a specified level and no data to contribute to this review.
Tsolaki 2002	Donepezil compared with rivastigmine in a non‐randomized study.
Wang 2001	Open label, randomized study, comparing rivastigmine with donepezil.
Werber 2002	Non‐randomized study of tacrine, donepezil or rivastigmine.

Data and analyses

Open in table viewer

Comparison 1. Cholinesterase inhibitor (optimum dose) vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 ADAS‐Cog mean changes in score from baseline at 6 months or later (ITT‐LOCF) Show forest plot	10	4236	Mean Difference (IV, Fixed, 95% CI)	‐2.37 [‐2.73, ‐2.02]
Open in figure viewer Analysis 1.1 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 1 ADAS‐Cog mean changes in score from baseline at 6 months or later (ITT‐LOCF).
2 MMSE mean change in score from baseline at 6 months or later (ITT‐LOCF) Show forest plot	9	3118	Mean Difference (IV, Fixed, 95% CI)	1.37 [1.13, 1.61]
Open in figure viewer Analysis 1.2 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 2 MMSE mean change in score from baseline at 6 months or later (ITT‐LOCF).
3 Activities of daily living (DAD) mean changes in score from baseline at 6 months or later (ITT‐LOCF) Show forest plot	2	669	Mean Difference (IV, Fixed, 95% CI)	4.39 [1.96, 6.81]
Open in figure viewer Analysis 1.3 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 3 Activities of daily living (DAD) mean changes in score from baseline at 6 months or later (ITT‐LOCF).
4 Activities of daily living (PDS) mean change in score from baseline at 6 months (ITT) Show forest plot	5	2188	Mean Difference (IV, Fixed, 95% CI)	2.46 [1.55, 3.37]
Open in figure viewer Analysis 1.4 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 4 Activities of daily living (PDS) mean change in score from baseline at 6 months (ITT).
5 Behavioural disturbance (NPI) mean changes from score from baseline at 6 months (ITT) Show forest plot	3	1005	Mean Difference (IV, Fixed, 95% CI)	‐2.44 [‐4.12, ‐0.76]
Open in figure viewer Analysis 1.5 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 5 Behavioural disturbance (NPI) mean changes from score from baseline at 6 months (ITT).
6 Global assessment with carer input (CIBIC‐Plus) (numbers improved or unchanged) at 6 months (ITT) Show forest plot	3	1306	Odds Ratio (M‐H, Fixed, 95% CI)	1.84 [1.47, 2.30]
Open in figure viewer Analysis 1.6 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 6 Global assessment with carer input (CIBIC‐Plus) (numbers improved or unchanged) at 6 months (ITT).
7 Global assessment with carer input (CIBIC‐Plus) (numbers improved) at 6 months (ITT) Show forest plot	8	3402	Odds Ratio (M‐H, Fixed, 95% CI)	1.56 [1.32, 1.85]
Open in figure viewer Analysis 1.7 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 7 Global assessment with carer input (CIBIC‐Plus) (numbers improved) at 6 months (ITT).
8 GBS‐global assessment mean change in score from baseline at 52 weeks (ITT) Show forest plot	1	282	Mean Difference (IV, Fixed, 95% CI)	‐3.26 [‐7.38, 0.86]
Open in figure viewer Analysis 1.8 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 8 GBS‐global assessment mean change in score from baseline at 52 weeks (ITT).
9 Time spent by carer assisting in IADL and PSMS (mean changes in score from baseline min/day) at 6 months (ITT) Show forest plot	1	221	Mean Difference (IV, Fixed, 95% CI)	‐52.4 [‐118.78, 13.98]
Open in figure viewer Analysis 1.9 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 9 Time spent by carer assisting in IADL and PSMS (mean changes in score from baseline min/day) at 6 months (ITT).
10 Total number of withdrawals before end of treatment at 6 months or later (ITT) Show forest plot	13	5143	Odds Ratio (M‐H, Fixed, 95% CI)	1.76 [1.54, 2.02]
Open in figure viewer Analysis 1.10 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 10 Total number of withdrawals before end of treatment at 6 months or later (ITT).
11 Total number of withdrawals due to an adverse event before end of treatment at 6 months or later (ITT) Show forest plot	13	5143	Odds Ratio (M‐H, Fixed, 95% CI)	2.32 [1.95, 2.76]
Open in figure viewer Analysis 1.11 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 11 Total number of withdrawals due to an adverse event before end of treatment at 6 months or later (ITT).
12 Number who suffered at least one adverse event before end of treatment at 6 months or later Show forest plot	12	4824	Odds Ratio (M‐H, Fixed, 95% CI)	2.51 [2.14, 2.95]
Open in figure viewer Analysis 1.12 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 12 Number who suffered at least one adverse event before end of treatment at 6 months or later.
13 Number who suffered at least one adverse event of abdominal pain before end of treatment at 6 months or later Show forest plot	7	2704	Odds Ratio (M‐H, Fixed, 95% CI)	1.95 [1.46, 2.61]
Open in figure viewer Analysis 1.13 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 13 Number who suffered at least one adverse event of abdominal pain before end of treatment at 6 months or later.
14 Number who suffered at least one adverse event of abnormal gait before end of treatment at 6 months or later Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	1.60 [0.63, 4.09]
Open in figure viewer Analysis 1.14 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 14 Number who suffered at least one adverse event of abnormal gait before end of treatment at 6 months or later.
15 Number who suffered at least one adverse event of abnormal dreams before end of treatment at 6 months or later Show forest plot	1	153	Peto Odds Ratio (Peto, Fixed, 95% CI)	5.38 [1.34, 21.55]
Open in figure viewer Analysis 1.15 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 15 Number who suffered at least one adverse event of abnormal dreams before end of treatment at 6 months or later.
16 Number who suffered at least one adverse event of accidental injury before end of treatment at 6 monthsorlater Show forest plot	3	651	Odds Ratio (M‐H, Fixed, 95% CI)	1.35 [0.86, 2.10]
Open in figure viewer Analysis 1.16 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 16 Number who suffered at least one adverse event of accidental injury before end of treatment at 6 monthsorlater.
17 Number who suffered at least one adverse event of agitation before end of treatment at 6 months or later Show forest plot	2	767	Odds Ratio (M‐H, Fixed, 95% CI)	0.95 [0.57, 1.56]
Open in figure viewer Analysis 1.17 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 17 Number who suffered at least one adverse event of agitation before end of treatment at 6 months or later.
18 Number who suffered at least one adverse event of anorexia before end of treatment at 6 months or later Show forest plot	10	4419	Odds Ratio (M‐H, Fixed, 95% CI)	3.75 [2.89, 4.87]
Open in figure viewer Analysis 1.18 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 18 Number who suffered at least one adverse event of anorexia before end of treatment at 6 months or later.
19 Number who suffered at least one adverse event of anxiety before end of treatment at 6 months or later Show forest plot	1	286	Odds Ratio (M‐H, Fixed, 95% CI)	2.01 [0.82, 4.90]
Open in figure viewer Analysis 1.19 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 19 Number who suffered at least one adverse event of anxiety before end of treatment at 6 months or later.
20 Number who suffered at least one adverse event of arthralgia before end of treatment at 6 months or later Show forest plot	2	498	Odds Ratio (M‐H, Fixed, 95% CI)	1.22 [0.62, 2.40]
Open in figure viewer Analysis 1.20 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 20 Number who suffered at least one adverse event of arthralgia before end of treatment at 6 months or later.
21 Number who suffered at least one adverse event of asthenia before end of treatment at 6 months or later Show forest plot	3	729	Odds Ratio (M‐H, Fixed, 95% CI)	2.47 [1.27, 4.81]
Open in figure viewer Analysis 1.21 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 21 Number who suffered at least one adverse event of asthenia before end of treatment at 6 months or later.
22 Number who suffered at least one adverse event of back pain before end of treatment at 6 months or later Show forest plot	1	290	Odds Ratio (M‐H, Fixed, 95% CI)	1.64 [0.62, 4.36]
Open in figure viewer Analysis 1.22 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 22 Number who suffered at least one adverse event of back pain before end of treatment at 6 months or later.
23 Number who suffered at least one adverse event of confusion before end of treatment at 6 months or later Show forest plot	4	1331	Odds Ratio (M‐H, Fixed, 95% CI)	0.83 [0.52, 1.32]
Open in figure viewer Analysis 1.23 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 23 Number who suffered at least one adverse event of confusion before end of treatment at 6 months or later.
24 Number who suffered at least one adverse event of conjunctivitis before end of treatment at 6 months or later Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	1.97 [0.70, 5.55]
Open in figure viewer Analysis 1.24 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 24 Number who suffered at least one adverse event of conjunctivitis before end of treatment at 6 months or later.
25 Number who suffered at least one adverse event of constipation before end of treatment at 6 months or later Show forest plot	1	286	Odds Ratio (M‐H, Fixed, 95% CI)	0.66 [0.23, 1.91]
Open in figure viewer Analysis 1.25 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 25 Number who suffered at least one adverse event of constipation before end of treatment at 6 months or later.
26 Number who suffered at least one adverse event of depression before end of treatment at 6 months or later Show forest plot	2	576	Odds Ratio (M‐H, Fixed, 95% CI)	1.58 [0.82, 3.04]
Open in figure viewer Analysis 1.26 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 26 Number who suffered at least one adverse event of depression before end of treatment at 6 months or later.
27 Number who suffered at least one adverse event of diarrhoea before end of treatment at 6 months or later Show forest plot	13	5173	Odds Ratio (M‐H, Fixed, 95% CI)	1.91 [1.59, 2.30]
Open in figure viewer Analysis 1.27 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 27 Number who suffered at least one adverse event of diarrhoea before end of treatment at 6 months or later.
28 Number who suffered at least one adverse event of dizziness before end of treatment at 6 months or later Show forest plot	12	4583	Odds Ratio (M‐H, Fixed, 95% CI)	1.99 [1.64, 2.42]
Open in figure viewer Analysis 1.28 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 28 Number who suffered at least one adverse event of dizziness before end of treatment at 6 months or later.
29 Number who suffered at least one adverse event of ecchymosis before end of treatment at 6 months or later Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	1.58 [0.54, 4.61]
Open in figure viewer Analysis 1.29 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 29 Number who suffered at least one adverse event of ecchymosis before end of treatment at 6 months or later.
30 Number who suffered at least one adverse event of fatigue before end of treatment at 6 months or later Show forest plot	1	319	Odds Ratio (M‐H, Fixed, 95% CI)	4.39 [1.21, 15.85]
Open in figure viewer Analysis 1.30 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 30 Number who suffered at least one adverse event of fatigue before end of treatment at 6 months or later.
31 Number who suffered at least one adverse event of fever before end of treatment at 6 months or later Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	0.87 [0.39, 1.93]
Open in figure viewer Analysis 1.31 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 31 Number who suffered at least one adverse event of fever before end of treatment at 6 months or later.
32 Number who suffered at least one adverse event of fracture before end of treatment at 6 months or later Show forest plot	5	2269	Odds Ratio (M‐H, Fixed, 95% CI)	0.96 [0.53, 1.74]
Open in figure viewer Analysis 1.32 $Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 32 Number who suffered at least one adverse event of fracture before end of treatment at 6 months or later.$ Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 32 Number who suffered at least one adverse event of fracture before end of treatment at 6 months or later.
33 Number who suffered at least one adverse event of haemorrhage before end of treatment at 6 months or later Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	1.02 [0.35, 3.02]
Open in figure viewer Analysis 1.33 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 33 Number who suffered at least one adverse event of haemorrhage before end of treatment at 6 months or later.
34 Number who suffered at least one adverse event of headache before end of treatment at 6 months or later Show forest plot	9	3686	Odds Ratio (M‐H, Fixed, 95% CI)	1.56 [1.27, 1.91]
Open in figure viewer Analysis 1.34 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 34 Number who suffered at least one adverse event of headache before end of treatment at 6 months or later.
35 Number who suffered at least one adverse event of hostility before end of treatment at 6 months or later Show forest plot	2	576	Odds Ratio (M‐H, Fixed, 95% CI)	0.96 [0.49, 1.87]
Open in figure viewer Analysis 1.35 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 35 Number who suffered at least one adverse event of hostility before end of treatment at 6 months or later.
36 Number who suffered at least one adverse event of increased cough before end of treatment at 6 months or later Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	1.19 [0.56, 2.52]
Open in figure viewer Analysis 1.36 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 36 Number who suffered at least one adverse event of increased cough before end of treatment at 6 months or later.
37 Number who suffered at least one adverse event of infection before end of treatment at 6 months or later Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	1.10 [0.51, 2.37]
Open in figure viewer Analysis 1.37 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 37 Number who suffered at least one adverse event of infection before end of treatment at 6 months or later.
38 Number who suffered at least one adverse event of insomnia before end of treatment at 6 months or later Show forest plot	7	2906	Odds Ratio (M‐H, Fixed, 95% CI)	1.49 [1.12, 2.00]
Open in figure viewer Analysis 1.38 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 38 Number who suffered at least one adverse event of insomnia before end of treatment at 6 months or later.
39 Number who suffered at least one adverse event of muscle cramp before end of treatment at 6 months or later Show forest plot	1	319	Odds Ratio (M‐H, Fixed, 95% CI)	13.32 [1.71, 103.74]
Open in figure viewer Analysis 1.39 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 39 Number who suffered at least one adverse event of muscle cramp before end of treatment at 6 months or later.
40 Number who suffered at least one adverse event of myasthenia before end of treatment at 6 months or later Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	2.10 [0.51, 8.64]
Open in figure viewer Analysis 1.40 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 40 Number who suffered at least one adverse event of myasthenia before end of treatment at 6 months or later.
41 Number who suffered at least one adverse event of nausea before end of treatment at 6 months or later Show forest plot	13	5089	Odds Ratio (M‐H, Fixed, 95% CI)	4.87 [4.13, 5.74]
Open in figure viewer Analysis 1.41 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 41 Number who suffered at least one adverse event of nausea before end of treatment at 6 months or later.
42 Number who suffered at least one adverse event of pain before end of treatment at 6 months or later Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	0.91 [0.47, 1.78]
Open in figure viewer Analysis 1.42 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 42 Number who suffered at least one adverse event of pain before end of treatment at 6 months or later.
43 Number who suffered at least one adverse event of peripheral oedema before end of treatment at 6 monthsorlater Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	2.08 [1.01, 4.28]
Open in figure viewer Analysis 1.43 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 43 Number who suffered at least one adverse event of peripheral oedema before end of treatment at 6 monthsorlater.
44 Number who suffered at least one adverse event of a rash before end of treatment at 6 months or later Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	0.72 [0.37, 1.42]
Open in figure viewer Analysis 1.44 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 44 Number who suffered at least one adverse event of a rash before end of treatment at 6 months or later.
45 Number who suffered at least one adverse event of a respiratory tract infection before end of treatment at 6 m Show forest plot	1	290	Odds Ratio (M‐H, Fixed, 95% CI)	1.02 [0.49, 2.12]
Open in figure viewer Analysis 1.45 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 45 Number who suffered at least one adverse event of a respiratory tract infection before end of treatment at 6 m.
46 Number who suffered at least one adverse event of rhinitis before end of treatment at 6 months or later Show forest plot	2	527	Odds Ratio (M‐H, Fixed, 95% CI)	1.38 [0.74, 2.58]
Open in figure viewer Analysis 1.46 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 46 Number who suffered at least one adverse event of rhinitis before end of treatment at 6 months or later.
47 Number who suffered at least one adverse event of skin ulcer before end of treatment at 6 months or later Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	1.51 [0.55, 4.12]
Open in figure viewer Analysis 1.47 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 47 Number who suffered at least one adverse event of skin ulcer before end of treatment at 6 months or later.
48 Number who suffered at least one adverse event of syncope before end of treatment at 6 months or later Show forest plot	5	2206	Odds Ratio (M‐H, Fixed, 95% CI)	1.90 [1.09, 3.33]
Open in figure viewer Analysis 1.48 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 48 Number who suffered at least one adverse event of syncope before end of treatment at 6 months or later.
49 Number who suffered at least one adverse event of tremor before end of treatment at 6 months or later Show forest plot	2	633	Odds Ratio (M‐H, Fixed, 95% CI)	6.82 [1.99, 23.37]
Open in figure viewer Analysis 1.49 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 49 Number who suffered at least one adverse event of tremor before end of treatment at 6 months or later.
50 Number who suffered at least one adverse event of urinary tract infection before end of treatment at 6 month Show forest plot	3	784	Odds Ratio (M‐H, Fixed, 95% CI)	0.90 [0.54, 1.48]
Open in figure viewer Analysis 1.50 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 50 Number who suffered at least one adverse event of urinary tract infection before end of treatment at 6 month.
51 Number who suffered at least one adverse event of vertigo before end of treatment at 6 months or later Show forest plot	1	286	Odds Ratio (M‐H, Fixed, 95% CI)	3.95 [1.08, 14.46]
Open in figure viewer Analysis 1.51 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 51 Number who suffered at least one adverse event of vertigo before end of treatment at 6 months or later.
52 Number who suffered at least one adverse event of vomiting before end of treatment at 6 months or later Show forest plot	11	4703	Odds Ratio (M‐H, Fixed, 95% CI)	4.82 [3.91, 5.94]
Open in figure viewer Analysis 1.52 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 52 Number who suffered at least one adverse event of vomiting before end of treatment at 6 months or later.
53 Number who suffered at least one adverse event of weight loss before end of treatment at 6 months or later Show forest plot	4	1358	Odds Ratio (M‐H, Fixed, 95% CI)	2.99 [1.89, 4.75]
Open in figure viewer Analysis 1.53 Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 53 Number who suffered at least one adverse event of weight loss before end of treatment at 6 months or later.

Open in table viewer

Comparison 2. Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 MMSE mean change from baseline (ITT‐LOCF) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.1 Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 1 MMSE mean change from baseline (ITT‐LOCF).
1.1 At 24 months	1	955	Mean Difference (IV, Fixed, 95% CI)	‐0.5 [‐1.33, 0.33]
2 Activities of daily living (ADCS‐ADL) (ITT‐LOCF) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.2 Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 2 Activities of daily living (ADCS‐ADL) (ITT‐LOCF).
2.1 At 24 months	1	929	Mean Difference (IV, Fixed, 95% CI)	‐2.08 [‐4.58, 0.42]
3 Behavioural disturbance (NPI‐10) (ITT‐LOCF) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.3 Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 3 Behavioural disturbance (NPI‐10) (ITT‐LOCF).
3.1 At 24 months	1	955	Mean Difference (IV, Fixed, 95% CI)	0.54 [‐1.68, 2.76]
4 Cognitive function (SIB) (ITT‐LOCF) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.4 Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 4 Cognitive function (SIB) (ITT‐LOCF).
4.1 At 24 months	1	954	Mean Difference (IV, Fixed, 95% CI)	‐0.61 [‐3.66, 2.44]
5 Global Deterioration Scale (GDS) (ITT‐LOCF) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.5 Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 5 Global Deterioration Scale (GDS) (ITT‐LOCF).
5.1 At 24 months	1	954	Mean Difference (IV, Fixed, 95% CI)	0.11 [‐0.00, 0.22]
6 Total number of patients who withdrew before end of treatment Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.6 Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 6 Total number of patients who withdrew before end of treatment.
6.1 At 104 weeks	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.64 [0.50, 0.83]
7 Total number of patients who withdrew before end of treatment due to an adverse event Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.7 Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 7 Total number of patients who withdrew before end of treatment due to an adverse event.
7.1 At 104 weeks	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.47 [0.32, 0.68]
8 Total number of patients who suffered an adverse event of nausea Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.8 Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 8 Total number of patients who suffered an adverse event of nausea.
8.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.37 [0.27, 0.50]
8.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	0.38 [0.23, 0.63]
9 Total number of patients who suffered an adverse event of vomiting Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.9 Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 9 Total number of patients who suffered an adverse event of vomiting.
9.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.16 [0.10, 0.24]
9.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	0.25 [0.15, 0.43]
10 Total number of patients who suffered an adverse event of agitation Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.10 Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 10 Total number of patients who suffered an adverse event of agitation.
10.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	1.46 [0.93, 2.30]
10.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	1.26 [0.79, 2.00]
11 Total number of patients who suffered an adverse event of anorexia Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.11 Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 11 Total number of patients who suffered an adverse event of anorexia.
11.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.42 [0.24, 0.72]
11.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	0.46 [0.24, 0.90]
12 Total number of patients who suffered an adverse event of diarrhoea Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.12 Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 12 Total number of patients who suffered an adverse event of diarrhoea.
12.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.81 [0.50, 1.30]
12.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	1.03 [0.60, 1.77]
13 Total number of patients who suffered an adverse event of weight loss Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.13 Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 13 Total number of patients who suffered an adverse event of weight loss.
13.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.28 [0.13, 0.61]
13.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	1.07 [0.67, 1.71]
14 Total number of patients who suffered an adverse event of headache Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.14 Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 14 Total number of patients who suffered an adverse event of headache.
14.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.84 [0.47, 1.48]
14.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	0.82 [0.37, 1.81]
15 Total number of patients who suffered an adverse event of a fall Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.15 Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 15 Total number of patients who suffered an adverse event of a fall.
15.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.38 [0.18, 0.81]
15.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	1.21 [0.75, 1.94]
16 Total number of patients who suffered an adverse event of hypertension Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.16 Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 16 Total number of patients who suffered an adverse event of hypertension.
16.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.34 [0.14, 0.81]
16.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	0.75 [0.40, 1.44]
17 Total number of patients who suffered an adverse event of depression Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.17 Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 17 Total number of patients who suffered an adverse event of depression.
17.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.51 [0.24, 1.11]
17.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	0.67 [0.34, 1.30]
18 Total number of patients who suffered an adverse event of a urinary tract infection Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.18 Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 18 Total number of patients who suffered an adverse event of a urinary tract infection.
18.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	1.63 [0.67, 3.96]
18.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	1.31 [0.70, 2.42]
19 Total number of patients who suffered an adverse event of aggression Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.19 Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 19 Total number of patients who suffered an adverse event of aggression.
19.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	1.57 [0.60, 4.09]
19.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	1.18 [0.64, 2.18]
20 Total number of patients who suffered a serious adverse event Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.20 Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 20 Total number of patients who suffered a serious adverse event.
20.1 At 104 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	1.03 [0.79, 1.35]
21 Total number of patients who died before end of treatment Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.21 Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 21 Total number of patients who died before end of treatment.
21.1 At 104 weeks	1	994	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.32 [0.78, 2.22]

Analysis 1.1

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 1 ADAS‐Cog mean changes in score from baseline at 6 months or later (ITT‐LOCF).

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Analysis 1.2

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 2 MMSE mean change in score from baseline at 6 months or later (ITT‐LOCF).

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Analysis 1.3

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 3 Activities of daily living (DAD) mean changes in score from baseline at 6 months or later (ITT‐LOCF).

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Analysis 1.4

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 4 Activities of daily living (PDS) mean change in score from baseline at 6 months (ITT).

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Analysis 1.5

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 5 Behavioural disturbance (NPI) mean changes from score from baseline at 6 months (ITT).

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Analysis 1.6

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 6 Global assessment with carer input (CIBIC‐Plus) (numbers improved or unchanged) at 6 months (ITT).

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Analysis 1.7

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 7 Global assessment with carer input (CIBIC‐Plus) (numbers improved) at 6 months (ITT).

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Analysis 1.8

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 8 GBS‐global assessment mean change in score from baseline at 52 weeks (ITT).

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Analysis 1.9

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 9 Time spent by carer assisting in IADL and PSMS (mean changes in score from baseline min/day) at 6 months (ITT).

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Analysis 1.10

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 10 Total number of withdrawals before end of treatment at 6 months or later (ITT).

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Analysis 1.11

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 11 Total number of withdrawals due to an adverse event before end of treatment at 6 months or later (ITT).

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Analysis 1.12

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 12 Number who suffered at least one adverse event before end of treatment at 6 months or later.

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Analysis 1.13

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 13 Number who suffered at least one adverse event of abdominal pain before end of treatment at 6 months or later.

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Analysis 1.14

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 14 Number who suffered at least one adverse event of abnormal gait before end of treatment at 6 months or later.

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Analysis 1.15

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 15 Number who suffered at least one adverse event of abnormal dreams before end of treatment at 6 months or later.

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Analysis 1.16

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 16 Number who suffered at least one adverse event of accidental injury before end of treatment at 6 monthsorlater.

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Analysis 1.17

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 17 Number who suffered at least one adverse event of agitation before end of treatment at 6 months or later.

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Analysis 1.18

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 18 Number who suffered at least one adverse event of anorexia before end of treatment at 6 months or later.

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Analysis 1.19

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 19 Number who suffered at least one adverse event of anxiety before end of treatment at 6 months or later.

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Analysis 1.20

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 20 Number who suffered at least one adverse event of arthralgia before end of treatment at 6 months or later.

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Analysis 1.21

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 21 Number who suffered at least one adverse event of asthenia before end of treatment at 6 months or later.

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Analysis 1.22

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 22 Number who suffered at least one adverse event of back pain before end of treatment at 6 months or later.

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Analysis 1.23

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 23 Number who suffered at least one adverse event of confusion before end of treatment at 6 months or later.

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Analysis 1.24

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 24 Number who suffered at least one adverse event of conjunctivitis before end of treatment at 6 months or later.

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Analysis 1.25

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 25 Number who suffered at least one adverse event of constipation before end of treatment at 6 months or later.

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Analysis 1.26

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 26 Number who suffered at least one adverse event of depression before end of treatment at 6 months or later.

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Analysis 1.27

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 27 Number who suffered at least one adverse event of diarrhoea before end of treatment at 6 months or later.

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Analysis 1.28

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 28 Number who suffered at least one adverse event of dizziness before end of treatment at 6 months or later.

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Analysis 1.29

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 29 Number who suffered at least one adverse event of ecchymosis before end of treatment at 6 months or later.

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Analysis 1.30

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 30 Number who suffered at least one adverse event of fatigue before end of treatment at 6 months or later.

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Analysis 1.31

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 31 Number who suffered at least one adverse event of fever before end of treatment at 6 months or later.

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$Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 32 Number who suffered at least one adverse event of fracture before end of treatment at 6 months or later.$

Analysis 1.32

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 32 Number who suffered at least one adverse event of fracture before end of treatment at 6 months or later.

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Analysis 1.33

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 33 Number who suffered at least one adverse event of haemorrhage before end of treatment at 6 months or later.

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Analysis 1.34

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 34 Number who suffered at least one adverse event of headache before end of treatment at 6 months or later.

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Analysis 1.35

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 35 Number who suffered at least one adverse event of hostility before end of treatment at 6 months or later.

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Analysis 1.36

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 36 Number who suffered at least one adverse event of increased cough before end of treatment at 6 months or later.

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Analysis 1.37

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 37 Number who suffered at least one adverse event of infection before end of treatment at 6 months or later.

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Analysis 1.38

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 38 Number who suffered at least one adverse event of insomnia before end of treatment at 6 months or later.

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Analysis 1.39

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 39 Number who suffered at least one adverse event of muscle cramp before end of treatment at 6 months or later.

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Analysis 1.40

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 40 Number who suffered at least one adverse event of myasthenia before end of treatment at 6 months or later.

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Analysis 1.41

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 41 Number who suffered at least one adverse event of nausea before end of treatment at 6 months or later.

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Analysis 1.42

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 42 Number who suffered at least one adverse event of pain before end of treatment at 6 months or later.

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Analysis 1.43

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 43 Number who suffered at least one adverse event of peripheral oedema before end of treatment at 6 monthsorlater.

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Analysis 1.44

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 44 Number who suffered at least one adverse event of a rash before end of treatment at 6 months or later.

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Analysis 1.45

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 45 Number who suffered at least one adverse event of a respiratory tract infection before end of treatment at 6 m.

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Analysis 1.46

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 46 Number who suffered at least one adverse event of rhinitis before end of treatment at 6 months or later.

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Analysis 1.47

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 47 Number who suffered at least one adverse event of skin ulcer before end of treatment at 6 months or later.

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Analysis 1.48

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 48 Number who suffered at least one adverse event of syncope before end of treatment at 6 months or later.

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Analysis 1.49

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 49 Number who suffered at least one adverse event of tremor before end of treatment at 6 months or later.

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Analysis 1.50

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 50 Number who suffered at least one adverse event of urinary tract infection before end of treatment at 6 month.

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Analysis 1.51

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 51 Number who suffered at least one adverse event of vertigo before end of treatment at 6 months or later.

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Analysis 1.52

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 52 Number who suffered at least one adverse event of vomiting before end of treatment at 6 months or later.

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Analysis 1.53

Comparison 1 Cholinesterase inhibitor (optimum dose) vs placebo, Outcome 53 Number who suffered at least one adverse event of weight loss before end of treatment at 6 months or later.

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Analysis 2.1

Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 1 MMSE mean change from baseline (ITT‐LOCF).

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Analysis 2.2

Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 2 Activities of daily living (ADCS‐ADL) (ITT‐LOCF).

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Analysis 2.3

Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 3 Behavioural disturbance (NPI‐10) (ITT‐LOCF).

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Analysis 2.4

Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 4 Cognitive function (SIB) (ITT‐LOCF).

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Analysis 2.5

Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 5 Global Deterioration Scale (GDS) (ITT‐LOCF).

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Analysis 2.6

Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 6 Total number of patients who withdrew before end of treatment.

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Analysis 2.7

Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 7 Total number of patients who withdrew before end of treatment due to an adverse event.

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Analysis 2.8

Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 8 Total number of patients who suffered an adverse event of nausea.

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Analysis 2.9

Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 9 Total number of patients who suffered an adverse event of vomiting.

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Analysis 2.10

Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 10 Total number of patients who suffered an adverse event of agitation.

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Analysis 2.11

Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 11 Total number of patients who suffered an adverse event of anorexia.

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Analysis 2.12

Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 12 Total number of patients who suffered an adverse event of diarrhoea.

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Analysis 2.13

Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 13 Total number of patients who suffered an adverse event of weight loss.

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Analysis 2.14

Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 14 Total number of patients who suffered an adverse event of headache.

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Analysis 2.15

Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 15 Total number of patients who suffered an adverse event of a fall.

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Analysis 2.16

Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 16 Total number of patients who suffered an adverse event of hypertension.

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Analysis 2.17

Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 17 Total number of patients who suffered an adverse event of depression.

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Analysis 2.18

Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 18 Total number of patients who suffered an adverse event of a urinary tract infection.

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Analysis 2.19

Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 19 Total number of patients who suffered an adverse event of aggression.

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Analysis 2.20

Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 20 Total number of patients who suffered a serious adverse event.

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Analysis 2.21

Comparison 2 Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day), Outcome 21 Total number of patients who died before end of treatment.

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Table 1. Description of included studies at baseline

Study	duration weeks	number of patients	mean age	% female	mean MMSE	dose mg/day donep.	phase	country	funded by
DON vs RIV/Bullock	104	988	75.9	69	15.1	10 donepezil, maximum 12 (in 2 doses) rivastigmine	‐	Australia, Canada, France, Germany, Italy, Spain, UK	Novartis
Donepezil‐302	24	473	73.4	62	19.0	5, 10	III	USA	Eisai
Donepezil‐304	24	818	71.7	57	20.0	5, 10	III	EUROPE	Eisai
Donepezil‐311	24	208	85.7	82	14.4	10	III	USA	Eisai
Donepezil‐402	24	153	74.0	53.6	24.1	10		USA	Eisai/Pfizer
Donepezil‐Feldman	24	290	73.6	61	11.8	10		CANADA, AUSTRALIA, FRANCE	Eisai/Pfizer
DON‐Nordic	52	286	72.5	64	19.3	10		EUROPE	Pfizer
GAL‐INT‐1	26	653	72.2	63	19.3	24, 32		EUROPE	UK NHS R&D health technology assessment programme
GAL‐USA‐1	26	636	70.7	62	19.3	24, 32		USA	Janssen
GAL‐USA‐10	22	978	76.9	64	17.8	8, 16, 24		USA	Janssen
Rivastigmine‐B303	26	725	72.0	59	20.0	6‐12	III	EUROPE, CANADA, USA	Novartis
Rivastigmine‐B304	26	677	71.4	59	18.5	2‐12	III	UK, IRELAND, AUSTRALIA, CANADA, RSA, ITALY	Novartis
Rivastigmine‐B351	26	702	74.1	56	20.0	6,9	III	USA	Novartis
Rivastigmine‐B352	26	699	74.5	61	19.7	6‐12	III	USA	Novartis

Table 1. Description of included studies at baseline

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Comparison 1. Cholinesterase inhibitor (optimum dose) vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 ADAS‐Cog mean changes in score from baseline at 6 months or later (ITT‐LOCF) Show forest plot	10	4236	Mean Difference (IV, Fixed, 95% CI)	‐2.37 [‐2.73, ‐2.02]

2 MMSE mean change in score from baseline at 6 months or later (ITT‐LOCF) Show forest plot	9	3118	Mean Difference (IV, Fixed, 95% CI)	1.37 [1.13, 1.61]

3 Activities of daily living (DAD) mean changes in score from baseline at 6 months or later (ITT‐LOCF) Show forest plot	2	669	Mean Difference (IV, Fixed, 95% CI)	4.39 [1.96, 6.81]

4 Activities of daily living (PDS) mean change in score from baseline at 6 months (ITT) Show forest plot	5	2188	Mean Difference (IV, Fixed, 95% CI)	2.46 [1.55, 3.37]

5 Behavioural disturbance (NPI) mean changes from score from baseline at 6 months (ITT) Show forest plot	3	1005	Mean Difference (IV, Fixed, 95% CI)	‐2.44 [‐4.12, ‐0.76]

6 Global assessment with carer input (CIBIC‐Plus) (numbers improved or unchanged) at 6 months (ITT) Show forest plot	3	1306	Odds Ratio (M‐H, Fixed, 95% CI)	1.84 [1.47, 2.30]

7 Global assessment with carer input (CIBIC‐Plus) (numbers improved) at 6 months (ITT) Show forest plot	8	3402	Odds Ratio (M‐H, Fixed, 95% CI)	1.56 [1.32, 1.85]

8 GBS‐global assessment mean change in score from baseline at 52 weeks (ITT) Show forest plot	1	282	Mean Difference (IV, Fixed, 95% CI)	‐3.26 [‐7.38, 0.86]

9 Time spent by carer assisting in IADL and PSMS (mean changes in score from baseline min/day) at 6 months (ITT) Show forest plot	1	221	Mean Difference (IV, Fixed, 95% CI)	‐52.4 [‐118.78, 13.98]

10 Total number of withdrawals before end of treatment at 6 months or later (ITT) Show forest plot	13	5143	Odds Ratio (M‐H, Fixed, 95% CI)	1.76 [1.54, 2.02]

11 Total number of withdrawals due to an adverse event before end of treatment at 6 months or later (ITT) Show forest plot	13	5143	Odds Ratio (M‐H, Fixed, 95% CI)	2.32 [1.95, 2.76]

12 Number who suffered at least one adverse event before end of treatment at 6 months or later Show forest plot	12	4824	Odds Ratio (M‐H, Fixed, 95% CI)	2.51 [2.14, 2.95]

13 Number who suffered at least one adverse event of abdominal pain before end of treatment at 6 months or later Show forest plot	7	2704	Odds Ratio (M‐H, Fixed, 95% CI)	1.95 [1.46, 2.61]

14 Number who suffered at least one adverse event of abnormal gait before end of treatment at 6 months or later Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	1.60 [0.63, 4.09]

15 Number who suffered at least one adverse event of abnormal dreams before end of treatment at 6 months or later Show forest plot	1	153	Peto Odds Ratio (Peto, Fixed, 95% CI)	5.38 [1.34, 21.55]

16 Number who suffered at least one adverse event of accidental injury before end of treatment at 6 monthsorlater Show forest plot	3	651	Odds Ratio (M‐H, Fixed, 95% CI)	1.35 [0.86, 2.10]

17 Number who suffered at least one adverse event of agitation before end of treatment at 6 months or later Show forest plot	2	767	Odds Ratio (M‐H, Fixed, 95% CI)	0.95 [0.57, 1.56]

18 Number who suffered at least one adverse event of anorexia before end of treatment at 6 months or later Show forest plot	10	4419	Odds Ratio (M‐H, Fixed, 95% CI)	3.75 [2.89, 4.87]

19 Number who suffered at least one adverse event of anxiety before end of treatment at 6 months or later Show forest plot	1	286	Odds Ratio (M‐H, Fixed, 95% CI)	2.01 [0.82, 4.90]

20 Number who suffered at least one adverse event of arthralgia before end of treatment at 6 months or later Show forest plot	2	498	Odds Ratio (M‐H, Fixed, 95% CI)	1.22 [0.62, 2.40]

21 Number who suffered at least one adverse event of asthenia before end of treatment at 6 months or later Show forest plot	3	729	Odds Ratio (M‐H, Fixed, 95% CI)	2.47 [1.27, 4.81]

22 Number who suffered at least one adverse event of back pain before end of treatment at 6 months or later Show forest plot	1	290	Odds Ratio (M‐H, Fixed, 95% CI)	1.64 [0.62, 4.36]

23 Number who suffered at least one adverse event of confusion before end of treatment at 6 months or later Show forest plot	4	1331	Odds Ratio (M‐H, Fixed, 95% CI)	0.83 [0.52, 1.32]

24 Number who suffered at least one adverse event of conjunctivitis before end of treatment at 6 months or later Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	1.97 [0.70, 5.55]

25 Number who suffered at least one adverse event of constipation before end of treatment at 6 months or later Show forest plot	1	286	Odds Ratio (M‐H, Fixed, 95% CI)	0.66 [0.23, 1.91]

26 Number who suffered at least one adverse event of depression before end of treatment at 6 months or later Show forest plot	2	576	Odds Ratio (M‐H, Fixed, 95% CI)	1.58 [0.82, 3.04]

27 Number who suffered at least one adverse event of diarrhoea before end of treatment at 6 months or later Show forest plot	13	5173	Odds Ratio (M‐H, Fixed, 95% CI)	1.91 [1.59, 2.30]

28 Number who suffered at least one adverse event of dizziness before end of treatment at 6 months or later Show forest plot	12	4583	Odds Ratio (M‐H, Fixed, 95% CI)	1.99 [1.64, 2.42]

29 Number who suffered at least one adverse event of ecchymosis before end of treatment at 6 months or later Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	1.58 [0.54, 4.61]

30 Number who suffered at least one adverse event of fatigue before end of treatment at 6 months or later Show forest plot	1	319	Odds Ratio (M‐H, Fixed, 95% CI)	4.39 [1.21, 15.85]

31 Number who suffered at least one adverse event of fever before end of treatment at 6 months or later Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	0.87 [0.39, 1.93]

32 Number who suffered at least one adverse event of fracture before end of treatment at 6 months or later Show forest plot	5	2269	Odds Ratio (M‐H, Fixed, 95% CI)	0.96 [0.53, 1.74]

33 Number who suffered at least one adverse event of haemorrhage before end of treatment at 6 months or later Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	1.02 [0.35, 3.02]

34 Number who suffered at least one adverse event of headache before end of treatment at 6 months or later Show forest plot	9	3686	Odds Ratio (M‐H, Fixed, 95% CI)	1.56 [1.27, 1.91]

35 Number who suffered at least one adverse event of hostility before end of treatment at 6 months or later Show forest plot	2	576	Odds Ratio (M‐H, Fixed, 95% CI)	0.96 [0.49, 1.87]

36 Number who suffered at least one adverse event of increased cough before end of treatment at 6 months or later Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	1.19 [0.56, 2.52]

37 Number who suffered at least one adverse event of infection before end of treatment at 6 months or later Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	1.10 [0.51, 2.37]

38 Number who suffered at least one adverse event of insomnia before end of treatment at 6 months or later Show forest plot	7	2906	Odds Ratio (M‐H, Fixed, 95% CI)	1.49 [1.12, 2.00]

39 Number who suffered at least one adverse event of muscle cramp before end of treatment at 6 months or later Show forest plot	1	319	Odds Ratio (M‐H, Fixed, 95% CI)	13.32 [1.71, 103.74]

40 Number who suffered at least one adverse event of myasthenia before end of treatment at 6 months or later Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	2.10 [0.51, 8.64]

41 Number who suffered at least one adverse event of nausea before end of treatment at 6 months or later Show forest plot	13	5089	Odds Ratio (M‐H, Fixed, 95% CI)	4.87 [4.13, 5.74]

42 Number who suffered at least one adverse event of pain before end of treatment at 6 months or later Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	0.91 [0.47, 1.78]

43 Number who suffered at least one adverse event of peripheral oedema before end of treatment at 6 monthsorlater Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	2.08 [1.01, 4.28]

44 Number who suffered at least one adverse event of a rash before end of treatment at 6 months or later Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	0.72 [0.37, 1.42]

45 Number who suffered at least one adverse event of a respiratory tract infection before end of treatment at 6 m Show forest plot	1	290	Odds Ratio (M‐H, Fixed, 95% CI)	1.02 [0.49, 2.12]

46 Number who suffered at least one adverse event of rhinitis before end of treatment at 6 months or later Show forest plot	2	527	Odds Ratio (M‐H, Fixed, 95% CI)	1.38 [0.74, 2.58]

47 Number who suffered at least one adverse event of skin ulcer before end of treatment at 6 months or later Show forest plot	1	208	Odds Ratio (M‐H, Fixed, 95% CI)	1.51 [0.55, 4.12]

48 Number who suffered at least one adverse event of syncope before end of treatment at 6 months or later Show forest plot	5	2206	Odds Ratio (M‐H, Fixed, 95% CI)	1.90 [1.09, 3.33]

49 Number who suffered at least one adverse event of tremor before end of treatment at 6 months or later Show forest plot	2	633	Odds Ratio (M‐H, Fixed, 95% CI)	6.82 [1.99, 23.37]

50 Number who suffered at least one adverse event of urinary tract infection before end of treatment at 6 month Show forest plot	3	784	Odds Ratio (M‐H, Fixed, 95% CI)	0.90 [0.54, 1.48]

51 Number who suffered at least one adverse event of vertigo before end of treatment at 6 months or later Show forest plot	1	286	Odds Ratio (M‐H, Fixed, 95% CI)	3.95 [1.08, 14.46]

52 Number who suffered at least one adverse event of vomiting before end of treatment at 6 months or later Show forest plot	11	4703	Odds Ratio (M‐H, Fixed, 95% CI)	4.82 [3.91, 5.94]

53 Number who suffered at least one adverse event of weight loss before end of treatment at 6 months or later Show forest plot	4	1358	Odds Ratio (M‐H, Fixed, 95% CI)	2.99 [1.89, 4.75]

Comparison 1. Cholinesterase inhibitor (optimum dose) vs placebo

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Comparison 2. Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 MMSE mean change from baseline (ITT‐LOCF) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.1 At 24 months	1	955	Mean Difference (IV, Fixed, 95% CI)	‐0.5 [‐1.33, 0.33]
2 Activities of daily living (ADCS‐ADL) (ITT‐LOCF) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

2.1 At 24 months	1	929	Mean Difference (IV, Fixed, 95% CI)	‐2.08 [‐4.58, 0.42]
3 Behavioural disturbance (NPI‐10) (ITT‐LOCF) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

3.1 At 24 months	1	955	Mean Difference (IV, Fixed, 95% CI)	0.54 [‐1.68, 2.76]
4 Cognitive function (SIB) (ITT‐LOCF) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

4.1 At 24 months	1	954	Mean Difference (IV, Fixed, 95% CI)	‐0.61 [‐3.66, 2.44]
5 Global Deterioration Scale (GDS) (ITT‐LOCF) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

5.1 At 24 months	1	954	Mean Difference (IV, Fixed, 95% CI)	0.11 [‐0.00, 0.22]
6 Total number of patients who withdrew before end of treatment Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

6.1 At 104 weeks	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.64 [0.50, 0.83]
7 Total number of patients who withdrew before end of treatment due to an adverse event Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

7.1 At 104 weeks	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.47 [0.32, 0.68]
8 Total number of patients who suffered an adverse event of nausea Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

8.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.37 [0.27, 0.50]
8.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	0.38 [0.23, 0.63]
9 Total number of patients who suffered an adverse event of vomiting Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

9.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.16 [0.10, 0.24]
9.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	0.25 [0.15, 0.43]
10 Total number of patients who suffered an adverse event of agitation Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

10.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	1.46 [0.93, 2.30]
10.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	1.26 [0.79, 2.00]
11 Total number of patients who suffered an adverse event of anorexia Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

11.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.42 [0.24, 0.72]
11.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	0.46 [0.24, 0.90]
12 Total number of patients who suffered an adverse event of diarrhoea Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

12.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.81 [0.50, 1.30]
12.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	1.03 [0.60, 1.77]
13 Total number of patients who suffered an adverse event of weight loss Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

13.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.28 [0.13, 0.61]
13.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	1.07 [0.67, 1.71]
14 Total number of patients who suffered an adverse event of headache Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

14.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.84 [0.47, 1.48]
14.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	0.82 [0.37, 1.81]
15 Total number of patients who suffered an adverse event of a fall Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

15.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.38 [0.18, 0.81]
15.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	1.21 [0.75, 1.94]
16 Total number of patients who suffered an adverse event of hypertension Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

16.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.34 [0.14, 0.81]
16.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	0.75 [0.40, 1.44]
17 Total number of patients who suffered an adverse event of depression Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

17.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	0.51 [0.24, 1.11]
17.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	0.67 [0.34, 1.30]
18 Total number of patients who suffered an adverse event of a urinary tract infection Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

18.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	1.63 [0.67, 3.96]
18.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	1.31 [0.70, 2.42]
19 Total number of patients who suffered an adverse event of aggression Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

19.1 By 16 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	1.57 [0.60, 4.09]
19.2 Between 16 and 104 weeks of treatment	1	857	Odds Ratio (M‐H, Fixed, 95% CI)	1.18 [0.64, 2.18]
20 Total number of patients who suffered a serious adverse event Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only

20.1 At 104 weeks of treatment	1	994	Odds Ratio (M‐H, Fixed, 95% CI)	1.03 [0.79, 1.35]
21 Total number of patients who died before end of treatment Show forest plot	1		Peto Odds Ratio (Peto, Fixed, 95% CI)	Subtotals only

21.1 At 104 weeks	1	994	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.32 [0.78, 2.22]

Comparison 2. Donepezil (10mg/day) vs rivastigmine (3‐12 mg/day)

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Referencias

Referencias de los estudios incluidos en esta revisión

DON‐302 {published data only}

DON‐304 {published and unpublished data}

DON‐311 {published data only}

DON‐402 {published data only}

DON‐Feldman {published data only}

DON‐Nordic {published data only}

DON vs RIV/Bullock {published data only}

GAL‐INT‐1 Wilcock {published data only}

GAL‐USA‐10 Tariot {published data only}

GAL‐USA‐1 Raskind {published data only}

RIV‐B303 {published data only}

RIV‐B304 {published data only}

RIV‐B351 {published data only}

RIV‐B352 {published data only}

Referencias de los estudios excluidos de esta revisión

AD2000 {published data only}

Donepezil‐203 {published data only}

Donepezil‐204 {published data only}

DON vs GAL/Jones {published data only}

DON vs GAL/Wilcock {published data only}

DON vs RIV/Wilkinson {published data only}

Fuschillo 2001 {published data only}

GAL‐INT‐10 {published data only}

GAL‐INT‐6Erkinjuntti {published data only}

Krishnan 2003 {published data only}

Mega 2002 {published data only}

Rozzini 2002 {published data only}

Shua‐Haim 2002b {published data only}

Study 312/314 {published data only}

Tsolaki 2002 {published data only}

Wang 2001 {published data only}

Werber 2002 {published data only}

Referencias adicionales

APA 1987

Birks 2005

Birks 2005b

Bucks 1996

Cummings 1994

DeJong 1989

Erkinjuntti 2002

Folstein 1975

Galasko 1997

Gottfries 1982

Gélinas 1999

Higgins 2003

Kumar 2000

Loy 2005

McKhann 1987

Olin 2005

Panisset 1994

Reisberg 1982

Rosen 1984

Schneider 1997

Wimo 1998

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Characteristics of excluded studies [ordered by study ID]

Data and analyses

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Idioma de la web

Instituciones a las que se accedió previamente

Usuarios institucionales

Instituciones a las que se accedió previamente

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