The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
Open-Label, Multicenter, Phase 3 Extension Study of the Safety and Efficacy of Donepezil in Patients With Alzheimer Disease
Abstract
BACKGROUND: Donepezil hydrochloride is a selective acetylcholinesterase inhibitor approved for the symptomatic treatment of mild to moderately severe Alzheimer disease (AD). Controlled clinical trials of up to 24 weeks have demonstrated that donepezil treatment (5 and 10 mg/d) significantly improves cognition and global function. OBJECTIVE: To investigate the long-term benefits of donepezil treatment in patients with AD. DESIGN: Multicenter, open-label, 144-week extension of 2 US phase 3, double-blind, placebo-controlled clinical trials: a 15-week study (12 weeks of treatment followed by a 3-week placebo washout) and a 30-week study (24 weeks of treatment followed by a 6-week placebo washout). INTERVENTIONS: All patients (N = 763) initially received donepezil, 5 mg/d, for 6 weeks, after which an increase to 10 mg/d was encouraged. MEASURES: Primary efficacy measures were the Alzheimer's Disease Assessment Scale-cognitive subscale and the Clinical Dementia Rating-Sum of the Boxes. RESULTS: After the shorter 3-week placebo washout, donepezil-associated benefits remained above original baseline values for an additional 24 weeks of open-label treatment. Benefits on Alzheimer's Disease Assessment Scale-cognitive subscale scores for patients who received 10 mg/d in the double-blind study were evident compared with the other groups for 108 weeks of open-label treatment. In contrast, donepezil-associated benefits were lost after the 6-week placebo washout, and scores decreased below original baseline values for all patient groups. Although scores improved relative to the new open-label study baseline scores after drug use was restarted, patients remained below original baseline values. The most common adverse events were associated with the nervous and digestive systems and were generally mild and transient; 17% of patient discontinuations were associated with adverse events. CONCLUSIONS: Donepezil is an effective and safe drug for the long-term symptomatic treatment of mild to moderately severe AD for up to 144 weeks (2.8 years), and sustained treatment may confer some advantages.
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“Longer term benefits, from 2 to 4 or more years have been demonstrated in open-label extension 69,[88][89][90] and long-term prospective observational clinical cohort studies.[91][92][93][94][95]”
From The Alzheimer’s Disease Clinical Spectrum (2019) · cites this paper as [69]
In the citing paper
“Discontinuation of ChEI treatment is, on aggregate, harmful.”
From The Alzheimer’s Disease Clinical Spectrum (2019) · cites this paper as [69]
In the citing paper
“Patients taken off, or those inconsistently taking, anti-AD medications progress more rapidly than those who continue treatments, particularly ChEIs.”
From The Alzheimer’s Disease Clinical Spectrum (2019) · cites this paper as [69]
Citations
Cites
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915
A New Clinical Scale for the Staging of Dementia
Hughes, C. P., Berg, L., Danziger, W., Coben, L. A., & Martin, R. L. (1982) · British Journal of Psychiatry · doi:10.1192/bjp.140.6.566 · Cited by 7,056
A new rating scale for Alzheimer's disease
(1984) · American Journal of Psychiatry · doi:10.1176/ajp.141.11.1356 · Cited by 4,175
A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease
Rogers, S. L., Farlow, M. R., Doody, R. S., Mohs, R., Friedhoff, L. T., & Donepezil Study Group* (1998) · Neurology · doi:10.1212/wnl.50.1.136 · Cited by 1,618
Rosler, M., Anand, R., Cicin-Sain, A., Gauthier, S., Agid, Y., Dal-Bianco, P., Stahelin, H. B., Hartman, R., Gharabawi, M., & Bayer, T. (1999) · BMJ · doi:10.1136/bmj.318.7184.633 · Cited by 943
Rogers, S. L. (1998) · Archives of Internal Medicine · doi:10.1001/archinte.158.9.1021 · Cited by 770
Rogers, S. L., & Friedhoff, L. T. (1996) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000106895 · Cited by 743
The Effects of Donepezil in Alzheimer’s Disease – Results from a Multinational Trial1
Burns, A. S., Rossor, M. N., Hecker, J. R., Gauthier, S. G., Petit, H., Möller, H. ‐., Rogers, S. L., & Friedhoff, L. T. (1999) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000017126 · Cited by 585
Rogers, S. L., Doody, R. S., Pratt, R. D., & Ieni, J. R. (2000) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(00)00067-5 · Cited by 268
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Diniz, B. S., Pinto, J. A., Gonzaga, M. L. C., Guimarães, F. M., Gattaz, W. F., & Forlenza, O. V. (2009) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-008-0864-1 · Cited by 61
“phase of the studies with long-term administration of ChEIs for up to 5 years have shown a slower cognitive decline loop and better global clinical status in the AD patients taking ChEIs in comparison to AD patients who were not on ChEIs or the expected cognitive decline for the subjects who never used ChEIs [ 11 , 34…”
ResultBorroni, B., Colciaghi, F., Pastorino, L., Archetti, S., Corsini, P., Cattabeni, F., Luca, M. D., & Padovani, A. (2002) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(02)00013-5 · Cited by 61
“First, it has been argued when treatment is continued with a slower decline over that the ApoE genotype effect is related with its main several years, hence it argues against a solely symptomatic function, the control of cholesterol homeostasis (Mahley, role (Doody et al., 2001).”
BackgroundRealistic Expectations: The Management of Severe Alzheimer Disease
Bullock, R. A., & Hammond, G. (2003) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-200307003-00004 · Cited by 61
“Evidence of the long-term cognitive benefits of donepezil comes from a study conducted by Doody et al.18 This multicenter, 144-week, open-label extension of two earlier doubleblind studies (of 15 and 30 weeks’ duration, followed by a placebo washout period of 3 or 6 weeks, respectively) evaluated the change from basel…”
BackgroundEconomics of dementia and pharmacoeconomics of dementia therapy
Fillit, H. M., & Hill, J. W. (2005) · The American Journal of Geriatric Pharmacotherapy · doi:10.1016/j.amjopharm.2005.03.005 · Cited by 58
Couteur, D. G. L., Hilmer, S. N., Glasgow, N., Naganathan, V., & Cumming, R. G. (2025) · Wiley eBooks · doi:10.1002/9781119870203.mpg006.pub2 · Cited by 59
Assessing Therapeutic Efficacy in a Progressive Disease
Johannsen, P., Salmon, É., Hampel, H. J., Xu, Y., Richardson, S., Qvitzau, S., & Schindler, R. J. (2006) · CNS Drugs · doi:10.2165/00023210-200620040-00005 · Cited by 58
Shega, J. W., Ellner, L., Lau, D. T., & Maxwell, T. L. (2009) · Journal of Palliative Medicine · doi:10.1089/jpm.2009.0059 · Cited by 59
Wolfson, C. M., Oremus, M., Shukla, V. K., Momoli, F., Demers, L., Perrault, A., & Moride, Y. (2002) · Clinical Therapeutics · doi:10.1016/s0149-2918(02)80004-2 · Cited by 57
Guidelines for the treatment of Alzheimer’s disease from the Italian Association of Psychogeriatrics
Caltagirone, C., Bianchetti, A., Luca, M. D., Mecocci, P., Padovani, A., Pirfo, E., Scapicchio, P., Senin, U., Trabucchi, M., & Musicco, M. (2005) · Drugs & Aging · doi:10.2165/00002512-200522001-00002 · Cited by 55
Changing Patient Characteristics and Survival Experience in an Alzheimer’s Center Patient Cohort
Doody, R. S., Pavlik, V., Massman, P. J., Kenan, M., Yeh, S., Powell, S. Z.-E., Cooke, N., Dyer, C. B., Demirovic, J., Waring, S. C., et al. (2005) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000087300 · Cited by 56
Jones, R. G., Sheehan, B., Phillips, P. P. J., Juszczak, E., Adams, J., Baldwin, A., Ballard, C. G., Banerjee, S., Barber, B., Bentham, P., et al. (2009) · Trials · doi:10.1186/1745-6215-10-57 · Cited by 55
“Typically, following a placebo washout period of 6 weeks at the end of a trial, the benefits of 24 weeks of donepezil treatment in terms of cognition and global function are lost [24].”
BackgroundPET Evidence of the Effect of Donepezil on Cognitive Performance in an Animal Model of Chemobrain
Lim, I., Joung, H.-Y., Yu, A., Shim, I., & Kim, J. S. (2016) · BioMed Research International · doi:10.1155/2016/6945415 · Cited by 55
“Donepezil is a reversible acetylcholinesterase inhibitor, which can facilitate the synaptic supply of acetylcholine, enhance cholinergic neural pathways, and consequently improve cognitive function [13, 14, 16, 20, 21].”
BackgroundPositron Emission Tomography Scans Obtained for the Evaluation of Cognitive Dysfunction
Silverman, D. H. S., Mosconi, L., Ercoli, L. M., Chen, W., & Small, G. W. (2008) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2008.02.006 · Cited by 55
Donepezil: a clinical review of current and emerging indications
Román, G. C., & Rogers, S. (2004) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.5.1.161 · Cited by 56
“8 years (144 weeks) and including a total of 941 patients, was an open-label, multicentre, Phase III extension trial [93] of two US controlled trials: the 15-week, 301 study [81] and the 30-week, 302 study [82].”
BackgroundDonepezil for Alzheimer’s disease
Benjamin, B., & Burns, A. S. (2007) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.7.10.1243 · Cited by 55
Seltzer, B. (2006) · Journal of International Medical Research · doi:10.1177/147323000603400401 · Cited by 54
Morphology of the inner structure of the hippocampal formation in Alzheimer disease.
Adachi, M., Kawakatsu, S., Hosoya, T., Otani, K., Honma, T., Shibata, A., & Sugai, Y. (2003) · PubMed Central · Cited by 54
Journal, C. (2006) · Core evidence · doi:10.2147/ce.s7447 · Cited by 53
“In this section, the content of several guidelines developed in the USA is described ( APA 1997; Doody et al. 2001b; California Workgroup 2002).”
InfluentialDonepezil for the Treatment of Behavioral Symptoms in Patients With Alzheimer's Disease
Paleacu, D., Mazeh, D., Mirecki, I., Even, M., & Barak, Y. (2002) · Clinical Neuropharmacology · doi:10.1097/00002826-200211000-00007 · Cited by 53
“8 years), and sustained treatment may confer some advantages (6).”
BackgroundLuttenberger, K., Hofner, B., & Graessel, E. (2012) · BMC Neurology · doi:10.1186/1471-2377-12-151 · Cited by 52
“Whereas it would be expected that the cognitive performance of Alzheimer patients who respond to drug therapy will inevitably deteriorate when the medication is withdrawn [8,9], preliminary evidence indicates that non-drug therapies may result in greater sustainability of cognition and the ability to carry out activit…”
BackgroundCholinergic modulation of working memory activity in primate prefrontal cortex
Zhou, X., Qi, X.-L., Douglas, K., Palaninathan, K., Kang, H. S., Buccafusco, J. J., Blake, D. T., & Constantinidis, C. (2011) · Journal of Neurophysiology · doi:10.1152/jn.00148.2011 · Cited by 53
Is donepezil therapy associated with reduced mortality in nursing home residents with dementia?
Gasper, M. C., Ott, B. R., & Lapane, K. L. (2005) · The American Journal of Geriatric Pharmacotherapy · doi:10.1016/j.amjopharm.2005.02.001 · Cited by 51
Can You Have Dementia With an MMSE Score of 30?
Shiroky, J. S., Schipper, H. M., Bergman, H., & Chertkow, H. M. (2007) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/1533317507304744 · Cited by 51
Tanaka, M., Namiki, C., Thuy, D. H. D., Yoshida, H., Kawasaki, K., Hashikawa, K., Fukuyama, H., & Kita, T. (2004) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2004.07.009 · Cited by 50
“However, the use of placebo controls was not ethically acceptable, because several clinical trials had demonstrated that donepezil improved cognitive and global functions in patients with AD [1–5].”
BackgroundMethodResultWallin, Å., Minthon, & Wattmo, C. (2011) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s24196 · Cited by 50
Farlow, M. R., Lilly, M. L., & for the ENA713 B352 Study Group (2005) · BMC Geriatrics · doi:10.1186/1471-2318-5-3 · Cited by 49
Delayed‐start analysis: Mild Alzheimer's disease patients in solanezumab trials, 3.5 years
Liu‐Seifert, H., Siemers, E., Holdridge, K. C., Andersen, S. W., Lipkovich, I. A., Carlson, C. D., Sethuraman, G., HOOG, S. L., Hayduk, R., Doody, R. S., et al. (2015) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2015.06.006 · Cited by 48
Do cholinergic therapies have disease‐modifying effects in Alzheimer's disease?
Sabbagh, M. N., Farlow, M. R., Relkin, N. R., & Beach, T. G. (2006) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2006.02.001 · Cited by 48
Treatment of Alzheimer Disease
Geldmacher, D. (2024) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000001503 · Cited by 51
Quality Indicators for the Care of Dementia in Vulnerable Elders
Feil, D. G., MacLean, C. H., & Sultzer, D. L. (2007) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2007.01335.x · Cited by 47
What Constitutes Clinical Evidence for Neuroprotection in Alzheimer Disease
Mori, E., Hashimoto, M., Krishnan, K., & Doraiswamy, P. M. (2006) · Alzheimer Disease & Associated Disorders · doi:10.1097/01.wad.0000213805.66811.31 · Cited by 45
“Mean change in ADAS-cog scores from baseline in 2 open-label, 144-week extensions of double-blind, placebo-controlled clinical trials stratified by treatment originally received in the double-blind study.(40) Beneficial effects on ADAS-cog scores for patients who received 10 mg/d in the double-blind study were evident…”
ResultParsons, C., Lim, W. Y., Loy, C. T., McGuinness, B., Passmore, P., Ward, S. A., & Hughes, C. M. (2021) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009081.pub2 · Cited by 49
A Large, Community-Based, Open-Label Trial of Donepezil in the Treatment of Alzheimer’s Disease
Relkin, N. R., Reichman, W. E., Orazem, J. P., & McRae, T. D. (2003) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000069988 · Cited by 46
Rivastigmine in Alzheimer Disease
Grossberg, G. T., Irwin, P., Satlin, A., Mesenbrink, P. G., & Spiegel, R. (2004) · American Journal of Geriatric Psychiatry · doi:10.1097/00019442-200407000-00010 · Cited by 46
Wallin, Å. K., Gustafson, L., Sjögren, M., Wattmo, C., & Minthon, L. (2004) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000079201 · Cited by 45
A population-based study of dosing and persistence with anti-dementia medications
Brewer, L., Bennett, K., McGreevy, C., & Williams, D. J. (2013) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-013-1483-y · Cited by 45
“In trials of ChIs and memantine for dementia, positive results were seen when the drug dosage was maximised [9, 12].”
BackgroundDonepezil (Aricept®) for treatment of Alzheimer´s disease and other dementing conditions
Geldmacher, D. (2004) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.4.1.5 · Cited by 45
Cognitive effects of donepezil therapy in patients with brain tumors: a pilot study
Correa, D. D., Kryza‐Lacombe, M., Baser, R. E., Beal, K. P., & DeAngelis, L. M. (2016) · Journal of Neuro-Oncology · doi:10.1007/s11060-015-2035-3 · Cited by 47
“such as donepezil have been found to produce benefits in cognitive and functional symptoms in patients with early Alzheimer’s disease [11, 12] and vascular dementia [13].”
Effects of Donepezil on Verbal Memory After Semantic Processing in Healthy Older Adults
FitzGerald, D. B., Crucian, G. P., Mielke, J. B., Shenal, B. V., Burks, D. W., Womack, K. B., Ghacibeh, G. A., Drago, V., Foster, P. S., Valenstein, E., et al. (2008) · Cognitive and Behavioral Neurology · doi:10.1097/wnn.0b013e3181799df1 · Cited by 43
“This result was seen for both 5mg and 10mg/d treatments.(31) A second possibility to explain the persistent treatment effect is that the increased levels of acetylcholine enhanced brain plasticity, altering the systems that mediate declarative memory and that these alterations persisted when the donepezil was withdraw…”
BackgroundSilverman, D. H. S., Cummings, J. L., Small, G. W., Gambhir, S. S., Chen, W., Czernin, J. G., & Phelps, M. E. (2002) · Molecular Imaging and Biology · doi:10.1016/s1536-1632(02)00016-1 · Cited by 43
How Many Patients Complete an Adequate Trial of Donepezil?
Roe, C. M., Anderson, M. J., & Spivack, B. (2002) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-200201000-00008 · Cited by 43
“These findings are concerning given the results of a recent open-label study, which demonstrated that temporary withdrawal of donepezil may lead to less effective long-term treatment (Doody et al., 2001).”
ResultImaging treatment effects in Alzheimer's disease
Venneri, A. (2007) · Magnetic Resonance Imaging · doi:10.1016/j.mri.2007.02.004 · Cited by 43
McRae, T. D., & Schwam, E. M. (2002) · Current Medical Research and Opinion · doi:10.1185/030079902125000949 · Cited by 42
Outcome of Alzheimer's disease: potential impact of cholinesterase inhibitors
Gillette-Guyonnet, S., Andrieu, S., Cortes, F., Nourhashemi, F., Cantet, C., Ousset, P.-J., Reynish, E., Grandjean, H., & Vellas, B. (2006) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/61.5.516 · Cited by 41
Pharmacokinetic and pharmacodynamic evaluation of donepezil for the treatment of Alzheimer's disease
Prvulovic, D., & Schneider, B. (2014) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2014.915028 · Cited by 41
“Similarly, two other open-label extension trials covering periods of 144 -- 240 weeks of active treatment were suggestive of treatment-related cognitive or functional benefits [89,90].”
BackgroundAcetylcholinesterase inhibitors may improve myelin integrity
Bartzokis, G. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.08.020 · Cited by 41
Managing Cognitive Dysfunction through the Continuum of Alzheimerʼs Disease
Delrieu, J., Piau, A., Caillaud, C., Voisin, T., & Vellas, B. J. (2011) · CNS Drugs · doi:10.2165/11539810-000000000-00000 · Cited by 44
Hartz, S., Getsios, D., Tao, S., Blume, S., & Maclaine, G. D. H. (2012) · BMC Neurology · doi:10.1186/1471-2377-12-2 · Cited by 39
“To improve on existing economic evaluations by including the effects of disease on behavior and function, data were analyzed from the CERAD (Consortium to Establish A Registry for Alzheimer’s Disease) registry [32], and seven donepezil clinical trials in AD [28-30,33-36], including data from open label extensions of t…”
MethodAlbani, D., Boneschi, F. M., Biella, G., Giacalone, G., Lupoli, S., Clerici, F., Benussi, L., Ghidoni, R., Galimberti, D., Squitti, R., et al. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-112123 · Cited by 39
Hogan, D. B., & Patterson, C. (2002) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s031716710000216x · Cited by 39
Safety and Effectiveness of Donepezil on Behavioral Symptoms in Patients With Alzheimer Disease
Carrasco, M. M., Agüera, L., Gil, P., Moríñigo, Á., & León, T. (2011) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e318212ab7a · Cited by 38
Alzheimer's disease: Seeing the signs early
Leifer, B. P. (2009) · Journal of the American Academy of Nurse Practitioners · doi:10.1111/j.1745-7599.2009.00436.x · Cited by 40
“from therapy for 6 weeks resulted in unrecoverable losses in function (Doody et al., 2001).”
BackgroundJelić, V., & Darreh‐Shori, T. (2010) · Clinical Medicine Insights Therapeutics · doi:10.4137/cmt.s5410 · Cited by 35
Review: Donepezil in Severe Alzheimer's Disease
Winblad, B. G. (2009) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/1533317509332094 · Cited by 38
Molinuevo, J. L., Berthier, M. L., & Rami, L. (2009) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2009.11.004 · Cited by 37
Joshi, S., & Morley, J. E. (2006) · Medical Clinics of North America · doi:10.1016/j.mcna.2006.05.014 · Cited by 38
Parsons, C., McCorry, N., Murphy, K. D., Byrne, S., O’Sullivan, D., O’Mahony, D., Passmore, P., Patterson, S. M., & Hughes, C. M. (2013) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.4006 · Cited by 36
“…therapy (Birks, 2006; Herrmann et al., 2007a; Herrmann and Gauthier, 2008) and reports of adverse events associated with discontinuation (Doody et al., 2001; Singh and Dudley, 2003; Holmes et al., 2004; Simpson et al., 2005; Okazaki et al., 2006; Daiello et al., 2009; Shega et al.,…”
BackgroundRockwood, K. J., Dai, D., & Mitnitski, A. (2007) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.1864 · Cited by 36
“Even though stability or slowing are desired, (Doody et al., 2001; Lyketsos et al., 2004; Raskind et al., 2004; Bullock and Dengiz, 2005; Farlow and Lilly, 2005) for most treated patients, dementia progresses (Birks, 2006).”
BackgroundIs Long-Term Treatment of Alzheimer’s Disease with Cholinesterase Inhibitor Therapy Justified?
Seltzer, B. (2007) · Drugs & Aging · doi:10.2165/00002512-200724110-00001 · Cited by 36
Errorless practice as a possible adjuvant to donepezil in Alzheimer’s disease
Rothi, L. J. G., Fuller, R., Leon, S. A., Kendall, D. L., MOORE, A. B., Wu, S. S., Crosson, B., Heilman, K. M., & Nadeau, S. E. (2009) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617709090201 · Cited by 35
“…multiple double-blind placebo-controlled studies have demonstrated that acetyl cholinesterase inhibitors are safe and delay cognitive decline in people with AD to a statistically signifi cant degree (Burns et al., 1999), the clinical effects of these drugs are less impressive (Doody et al., 2001 ).”
BackgroundResultDrug Therapy: Alzheimer's Disease
Jeffrey, L. P. (2004) · Cited by 36
Ott, B. R., Blake, L. M., Kagan, E., Resnick, M., & for the Memantine MEM-MD-11AB Study Group (2007) · Journal of Neurology · doi:10.1007/s00415-006-0374-x · Cited by 35
“Thus, the safety and tolerability of long-term maintenance therapy with memantine compares favorably with open label studies of cholinesterase inhibitors that have reported incidences of nausea and diarrhea in 10% or more patients [ 8 , 16].”
Drug persistency of cholinesterase inhibitors for patients with dementia of Alzheimer type in Korea
Ahn, S.-H., Choi, N., Kim, Y., Seong, J.-M., Shin, J., Jung, S.-Y., & Park, B. (2014) · Archives of Pharmacal Research · doi:10.1007/s12272-014-0500-8 · Cited by 35
“After a 6-week placebo washout, the benefits of 24 weeks of treatment with donepezil were completely lost, suggesting that interrupting treatment for as long as 6 weeks might result in patients not returning to the levels of cognition and global function that they had attained before interruption (Doody et al. 2001).”
Pathogenic Feed-Forward Mechanisms in Alzheimer’s and Parkinson’s Disease Converge on GSK-3
Albeely, A. M., Ryan, S. D., & Perreault, M. L. (2018) · Brain Plasticity · doi:10.3233/bpl-180078 · Cited by 33
Progress update: Pharmacological treatment of Alzheimer’s disease
Hogan, D. B. (2007) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.a931 · Cited by 32
Moulin-Romsee, G., Maes, A., Silverman, D. H. S., Mortelmans, L., & Laere, K. V. (2005) · European Journal of Neurology · doi:10.1111/j.1468-1331.2004.00940.x · Cited by 34
“We have used the standard methods for decision analysis (Drummond et al., 1997; Gambhir and Schwimmer, 2000) to quantify the major outcomes of this analysis: overall costs, costs per accurate diagnosis and number of accurate diagnoses.”
MethodMild cognitive impairment: new neuropsychological and pharmacological target
Rivas-Vazquez, R. A., Mendez, C., Rey, G. J., & Carrazana, E. J. (2003) · Archives of Clinical Neuropsychology · doi:10.1016/s0887-6177(02)00167-1 · Cited by 37
Pharmacologic treatment of adolescent and child schizophrenia
Young, C., & Findling, R. L. (2004) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.4.1.53 · Cited by 31
Social and family load of Alzheimer’s disease
Marešová, P., Mohelská, H., & Kuča, K. (2015) · Applied Economics · doi:10.1080/00036846.2015.1111986 · Cited by 31
“For example, aged 65 plus could significantly reduce the number of diagnosis by increasing their exercise rate by 50% (Doody et al. 2001).”
BackgroundAlzheimer's Disease: Current Pharmacotherapy in the Context of Patient and Family Needs
Geldmacher, D. (2003) · Journal of the American Geriatrics Society · doi:10.1046/j.1365-2389.2003.5154.x · Cited by 29
Patterns of cholinesterase-inhibitor use in the nursing home setting: A retrospective analysis
Dybicz, S. B., Keohane, D. J., Erwin, W. G., McRae, T. D., & Shah, S. N. (2006) · The American Journal of Geriatric Pharmacotherapy · doi:10.1016/j.amjopharm.2006.06.002 · Cited by 28
Clinically tested drugs for Alzheimer?s disease
McGeer, E. G., & McGeer, P. L. (2003) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.12.7.1143 · Cited by 28
Homma, A., Imai, Y., Tago, H., Asada, T., Shigeta, M., Iwamoto, T., Takita, M., Arimoto, I., Koma, H., Takase, T., et al. (2009) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000203887 · Cited by 27
The long‐term efficacy and tolerability of donepezil in patients with vascular dementia
Wilkinson, D. G., Román, G. C., Salloway, S., Hecker, J. R., Boundy, K. L., Kumar, D., Posner, H. B., & Schindler, R. J. (2009) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2340 · Cited by 27
“This mirrors what has been observed in clinical studies of AD patients, a population in which safety data are available for up to 4.9 years (Doody et al., 2001b).”
BackgroundResultInfluentialClinical effects of high oral dose of donepezil for patients with Alzheimer's disease in Japan
Nozawa, M., Ichimiya, Y., Nozawa, E., Utumi, Y., Sugiyama, H., Murayama, N., Iseki, E., & Arai, H. (2009) · Psychogeriatrics · doi:10.1111/j.1479-8301.2009.00291.x · Cited by 27
Gallucci, M., Spagnolo, P., Aricò, M., & Grossi, E. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-150747 · Cited by 26
“8 years [18], and in a “US multicenter open-label study” it was even shown to be efficacious over a period up to 4.”
Relkin, N. R. (2007) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.7.6.735 · Cited by 27
Pharmacologic Treatment Expectations in the Management of Dementia with Lewy Bodies
Kaufer, D. (2003) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000074680 · Cited by 26
Arjmandi-Rad, S., Nieland, J. D., Goozee, K. G., & Vaseghi, S. (2023) · Neurological Sciences · doi:10.1007/s10072-023-07114-y · Cited by 26
“It has been suggested that AChEIs via inhibition of acetylcholinesterase can significantly slow down or attenuate the underlying pathophysiologic process of AD, both before and after the diagnosis [41, 42].”
Efficacy of memantine in PDD and DLB: an extension study including washout and open-label treatment
Johansson, C., Ballard, C. G., Hansson, O., Palmqvist, S., Minthon, L., Aarsland, D., & Londos, E. (2010) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2516 · Cited by 26
“This is consistent with washout results upon withdrawal of ChEIs in Alzheimer patients (Greenberg et al., 2000; Doody et al., 2001; Burns et al., 2007; Homma et al., 2009).”
ResultLong-Term Cholinesterase Inhibitor Therapy for Alzheimer's Disease
Geldmacher, D. (2003) · The Primary Care Companion For CNS Disorders · doi:10.4088/pcc.v05n0602 · Cited by 24
The Cost-Benefit of Cholinesterase Inhibitors in Mild to Moderate Dementia
Wu, G. H., Lanctôt, K. L., Herrmann, N., Moosa, S., & OH, P. I. (2003) · CNS Drugs · doi:10.2165/00023210-200317140-00004 · Cited by 24
Tariot, P. N., Braeckman, R., & Oh, C. (2022) · Journal of Alzheimer's Disease · doi:10.3233/jad-220530 · Cited by 24
Atri, A., Rountree, S. D., López, O. L., & Doody, R. S. (2012) · Neurodegenerative Diseases · doi:10.1159/000335156 · Cited by 23
Assessing physician attitudes and perceptions of Alzheimer's disease across Europe
Martínez‐Lage, P., Frölich, L., Knox, S., & Berthet, K. (2010) · The journal of nutrition health & aging · doi:10.1007/s12603-010-0265-9 · Cited by 23
Barchielli, A., Buiatti, E., Balzi, D., Santoro, G. M., Carrabba, N., Fabiani, P., Maci, M., Margheri, M., Mangani, I., Monami, M., et al. (2004) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2004.52368.x · Cited by 23
Donepezil in the treatment of Alzheimer's disease
Rocca, P., Cocuzza, E., Marchiaro, L., & Bogetto, F. (2002) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(01)00283-4 · Cited by 23
Cholinesterase inhibitor use in Alzheimer's disease: the EPIFARM‐Elderly Project
Franchi, C., Lucca, U., Tettamanti, M., Riva, E., Fortino, I., Bortolotti, A., Merlino, L. G., Pasina, L., & Nobili, A. (2011) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.2124 · Cited by 23
Häger, K., Calabrese, P., Frölich, L., Göbel, C., & Berger, F. M. (2003) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000068786 · Cited by 22
Zhang, R. Y., Leon, A. C., Chuang‐Stein, C., & Romano, S. J. (2011) · Clinical Trials · doi:10.1177/1740774510392255 · Cited by 21
“, the ADAS-cog level for the placebo arm increased to the same level as the active arm within the first 6 weeks despite the 6-month delay in starting donepezil) [25].”
BackgroundResultWattmo, C., Hansson, O., Wallin, Å. K., Londos, E., & Minthon, L. (2008) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000152911 · Cited by 21
“Furthermore, extension studies of placebo-controlled trials have shown that the effect of ChEI may last even longer [”
BackgroundThe pharmacological management of Alzheimer's disease
Bishara, D., Sauer, J., & Taylor, D. M. (2015) · Progress in Neurology and Psychiatry · doi:10.1002/pnp.387 · Cited by 21
Review of drug development and therapeutic role of cholinesterase inhibitors in Alzheimer's disease
Sramek, J. J., Zarotsky, V., & Cutler, N. R. (2002) · Drug Development Research · doi:10.1002/ddr.10087 · Cited by 21
“Adverse events were generally mild and transient, and 17% of patients discontinued the study for adverse events [Doody et al., 2001].”
BackgroundDifferences in Medication Use in the Alzheimerʼs Disease Neuroimaging Initiative
Epstein, N. U., Saykin, A. J., Risacher, S. L., Gao, S., & Farlow, M. R. (2010) · Drugs & Aging · doi:10.2165/11538260-000000000-00000 · Cited by 21
Thibault, C. S., Stillman, I. Ö., Chen, S., Getsios, D., Proskorovsky, I., Hernandez, L. G., & Dixit, S. (2015) · Journal of Medical Economics · doi:10.3111/13696998.2015.1063501 · Cited by 20
Clinical guidelines «Cognitive disorders in the elderly and senile persons»
Tkacheva, O. N., Yahno, N. N., Незнанов, Н. Г., Шпорт, С. В., Shamalov, N. A., Levin, O. S., Kostyuk, G. P., Gusev, E. I., Martynov, M. Y., Si, G., et al. (2025) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro2025125337 · Cited by 22
Hanada, K., Hosono, M., Kudo, T., Hitomi, Y., Yagyu, Y., Kirime, E., Komeya, Y., Tsujii, N., Hitomi, K., & Nishimura, Y. (2006) · Nuclear Medicine Communications · doi:10.1097/00006231-200606000-00010 · Cited by 19
Diagnosing Dementia in Long-Term Care Facilities
Singer, C. M., & Luxenberg, J. S. (2003) · Journal of the American Medical Directors Association · doi:10.1016/s1525-8610(04)70404-1 · Cited by 21
Doody, R. S. (2007) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2007.10.010 · Cited by 19
Liu, M., Zhang, Y., Huo, Y. R., Liu, S., Liu, S., Wang, J., Wang, C., Wang, J., & Ji, Y. (2014) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000367596 · Cited by 18
Metadata
- Authors
- Doody, R. S.
- Affiliations
- Baylor College of Medicine (US)
- Corresponding author
- Doody, Rachelle S.
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2001-03-01
- Volume
- 58
- Issue
- 3
- Pages
- 427
- ISSN
- 0003-9942 (ISSN-L)
- OpenAlex
- W2064649894
- Cited by
- 362
- References
- 14
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 2 · 2023: 6 · 2022: 2 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 11 · 2017: 5 · 2016: 8 · 2015: 14 · 2014: 7 · 2013: 13 · 2012: 11
- FWCI
- 21.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- donepezil, Alzheimer's disease, acetylcholinesterase inhibitors, long-term treatment, cognitive function, Clinical Dementia Rating, adverse events, drug discontinuation, symptomatic treatment
- MeSH terms
- Donepezil, Aged, Alzheimer Disease, Cholinesterase Inhibitors, Double-Blind Method, Female, Humans, Indans, Male, Middle Aged, Neuropsychological Tests, Piperidines, Treatment Outcome
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