The comparative efficacy and safety of cholinesterase inhibitors in patients with mild-to-moderate Alzheimer’s disease: A Bayesian network meta-analysis
Open accessAbstract
BACKGROUND: Comparative evidence for efficacy and safety of second-generation cholinesterase inhibitors (ChEIs) is still sparse. OBJECTIVES: The purpose of this research is to compare three ChEIs, donepezil, galantamine and rivastigmine, in patients with mild-to-moderate Alzheimer's disease (AD). METHODS: We conducted a systematic review for published articles and included randomised, double-blind, placebo-controlled trials and head-to-head randomised trials evaluating the efficacy and safety of ChEIs in patients with AD. We examined Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-Cog), Neuropsychiatric Inventory (NPI), Clinician's Interview-Based Impression of Change plus caregiver's input (CIBIC+) and Clinical Global Impression of Change (CGIC) as efficacy endpoints. Withdrawals due to adverse events and number of patients experiencing nausea, vomiting, diarrhoea and dizziness were examined as safety profiles. Network meta-analyses were sequentially performed for efficacy and safety outcomes based on drug/dose treatment conditions. RESULTS: Among the 21 trials included, network meta-analysis showed that all treatments were significantly more efficacious than placebo in cognition measured by ADAS-Cog. All treatments except galantamine were significantly more efficacious than placebo in global change in CIBIC+ or CGIC. Across all conditions, no significant efficacy was observed in neuropsychiatric symptoms measured by NPI. Derived hierarchies in the efficacy of treatment conditions were variables across efficacy and safety. CONCLUSIONS: Our analysis is the first attempt to incorporate available direct and indirect evidence. The results suggest that ChEIs should have significant efficacy for cognition and global change assessment, but the efficacy on neuropsychiatric symptoms is questionable in patients with mild-to-moderate AD.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Alzheimer's disease patients receiving cholinesterase inhibitors experience adverse effects such as nausea, vomiting, diarrhea and dizziness.
“AD patients receiving cholinesterase inhibitors experience adverse effects like nausea, vomiting, diarrhea, dizziness, etc. [21].”
From Indian Medicinal Herbs and Formulations for Alzheimer’s Disease, from Traditional Knowledge to Scientific Assessment (2020) · cites this paper as [21]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Conducting Meta-Analyses in <i>R</i> with the <b>metafor</b> Package
Viechtbauer, W. (2010) · Journal of Statistical Software · doi:10.18637/jss.v036.i03 · Cited by 20,464 · cited 1× · see citing works
“The meta-analyses were performed using Metafor package (Viechtbauer, 2010) in R.”
MethodThe Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia
Cummings, J. L., Mega, M., Gray, K., Rosenberg-Thompson, S., Carusi, D. A., & Gornbein, J. (1994) · Neurology · doi:10.1212/wnl.44.12.2308 · Cited by 7,568 · cited 4× · see citing works
“We included results from randomised, doubleblinded, placebo-controlled trials (RCTs) evaluating the efficacy of ChEIs in patients with mild-tomoderate AD with at least one of the following assessments: (1) Alzheimer’s Disease Assessment Scale, cognitive subscale (ADAS-Cog; Rosen and Mohs, 1984), (2) Neuropsychiatric I…”
MethodInfluentialGeneral methods for monitoring convergence of iterative simulations
Brooks, S. P., & Gelman, A. (1998) · Journal of Computational and Graphical Statistics · doi:10.1080/10618600.1998.10474787 · Cited by 6,045 · cited 1× · see citing works
“The model convergence was evaluated by visually inspecting the iteration plot and the potential scale reduction factor (Brooks and Gelman, 1997).”
MethodA new rating scale for Alzheimer's disease
(1984) · American Journal of Psychiatry · doi:10.1176/ajp.141.11.1356 · Cited by 4,175 · see citing works
Salanti, G., Ades, A. E., & Ioannidis, J. P. A. (2011) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2010.03.016 · Cited by 3,766 · cited 1× · see citing works
“The hierarchy between drugs was estimated by the surface under the cumulative ranking (Salanti et al., 2014), which was computed by the ranking probabilities of the frequency table of iteration results.”
MethodGeneral Methods for Monitoring Convergence of Iterative Simulations
Brooks, S. P., & Gelman, A. (1998) · Journal of Computational and Graphical Statistics · doi:10.2307/1390675 · Cited by 2,017 · see citing works
Cholinesterase inhibitors for Alzheimer's disease
Birks, J. S. (2006) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd005593 · Cited by 1,906 · see citing works
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 · see citing works
Placebo Response in Studies of Major Depression: Variable, Substantial, and Growing
Walsh, B. T., Seidman, S. N., Sysko, R., & Gould, M. (2002) · JAMA · doi:10.1001/jama.287.14.1840 · Cited by 1,109 · cited 1× · see citing works
“Increasing placebo effects over time were found in antipsychotic and antidepressant trials (Walsh et al., 2002; Rutherford et al., 2014).”
BackgroundEvaluation of networks of randomized trials
Salanti, G., Higgins, J. P., Ades, A., & Ioannidis, J. P. (2008) · Statistical Methods in Medical Research · doi:10.1177/0962280207080643 · Cited by 1,078 · cited 1× · see citing works
“The network meta-analysis (NMA) is a metaanalysis in which multiple treatments are compared using both direct comparisons of interventions within randomised controlled trials and indirect comparisons across trials based on a common comparator (Salanti et al., 2008).”
MethodPractice Guideline for the Treatment of Patients With Obsessive-Compulsive Disorder
(2008) · APA Practice Guidelines for the Treatment of Psychiatric Disorders: Comprehensive Guidelines and Guideline Watches · doi:10.1176/appi.books.9780890423363.149114 · Cited by 1,028 · see citing works
The National Institute for Clinical Excellence (NICE)
Rodgers, A.-T. (2002) · Annals of the Rheumatic Diseases · doi:10.1136/ard.61.suppl_2.ii92 · Cited by 976 · see citing works
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 · see citing works
A 5-month, randomized, placebo-controlled trial of galantamine in AD
Tariot, P. N., Solomon, P. R., Morris, J. C., Kershaw, P. R., Lilienfeld, S., Ding, C., & the Galantamine USA- Study Group (2000) · Neurology · doi:10.1212/wnl.54.12.2269 · Cited by 915 · see citing works
Pharmacological Treatment of Neuropsychiatric Symptoms of Dementia: A Review of the Evidence
Sink, K. M., Holden, K. F., & Yaffe, K. (2005) · JAMA · doi:10.1001/jama.293.5.596 · Cited by 910 · see citing works
Raskind (2000) · doi:10.1212/wnl.54.12.2261 · Cited by 870 · see citing works
Automating network meta‐analysis
van Valkenhoef, G., Lu, G., de Brock, B., Hillege, H. L., Ades, A. E., & Welton, N. J. (2012) · Research Synthesis Methods · doi:10.1002/jrsm.1054 · Cited by 793 · cited 1× · see citing works
“The analyses were performed in the Bayesian hierarchical model framework with Markov chain Monte Carlo estimation using the GeMTC package (van Valkenhoef et al., 2012) in R.”
MethodRogers, S. L. (1998) · Archives of Internal Medicine · doi:10.1001/archinte.158.9.1021 · Cited by 770 · see citing works
Demystifying trial networks and network meta-analysis
Mills, E. J., Thorlund, K., & Ioannidis, J. P. A. (2013) · BMJ · doi:10.1136/bmj.f2914 · Cited by 742 · cited 1× · see citing works
“Although there are concerns about methodological issues of sample size, power, sources of bias and heterogeneity, for many comparisons, the network meta-analysis may yield more reliable and definitive results than would a pairwise meta-analysis (Mills et al., 2013).”
ResultSchneider, L., Olin, J. T., Doody, R. S., Clark, C. M., Morris, J. C., Reisberg, ., Schmitt, F. A., Grundman, M., Thomas, R. G., & Ferris, S. H. (1997) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-199700112-00004 · Cited by 647 · cited 1× · see citing works
“…subscale (ADAS-Cog; Rosen and Mohs, 1984), (2) Neuropsychiatric Inventory (NPI; Cummings et al., 1994), (3) Clinician’s Interview-Based Impression of Change scale plus caregiver’s input (CIBIC+; Knopman et al., 1994) and (4) Clinical Global Impression of Change (CGIC; Schneider et al., 1997).”
BackgroundWilcock, G. K., Lilienfeld, S., & Gaens, E. (2000) · BMJ · doi:10.1136/bmj.321.7274.1445 · Cited by 623 · see citing works
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 · see citing works
Hansen, R. A., Webb, A. P., Moore, C. G., Gartlehner, G., Jonas, D. E., & Morgan, L. C. (2020) · PubMed Central · doi:10.17615/ae8c-2p76 · Cited by 523 · see citing works
Tan, C.-C., Yu, J.-T., Wang, H.-F., Tan, M.-S., Meng, X.-F., Wang, C., Jiang, T., Zhu, X.-C., & Tan, L. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-132690 · Cited by 484 · see citing works
Corey-Bloom, J. (1998) · Medical Entomology and Zoology · Cited by 467 · see citing works
Winblad, B. G., Cummings, J. L., Andreasen, N., Grossberg, G. T., ONOFRJ, M. C., Sadowsky, C., Zechner, S., Nagel, J., & Lane, R. M. (2007) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.1788 · Cited by 286 · cited 1× · see citing works
“A study (Winblad et al., 2007) of oral versus rivastigmine patch also demonstrated the superior tolerability of the patch.”
BackgroundPsychiatric Symptoms Vary With the Severity of Dementia in Probable Alzheimer's Disease
Lopez, O. L., Becker, J. T., Sweet, R. A., Klunk, W., Kaufer, D. I., Saxton, J., Habeych, M., & DeKosky, S. T. (2003) · The Journal of Neuropsychiatry and Clinical Neurosciences · doi:10.1176/jnp.15.3.346 · Cited by 286 · cited 1× · see citing works
“Another recent study demonstrated that mood symptoms would be developed in the early course of the disease; on the other hand, psychotic symptoms and agitation would characterise the middle-to-late stages of dementia in patients with AD (Lopez et al., 2003).”
BackgroundTreatment of patients with substance use disorders, second edition. American Psychiatic Association.
Kleber, H. D., Weiss, R. D., Anton, R. F., George, T. P., Greenfield, S. F., Kosten, T. R., O’Brien, C. P., Rounsaville, B. J., Strain, E. C., Ziedonis, D. M., et al. (2006) · PubMed · Cited by 265 · see citing works
Bullock, R. A., Touchon, J., Bergman, H., Gambina, G., He, Y., Rapatz, G., Nagel, J., & Lane, R. M. (2005) · Current Medical Research and Opinion · doi:10.1185/030079905x56565 · Cited by 228 · see citing works
Rodda, J. E., Morgan, S., & Walker, Z. (2009) · International Psychogeriatrics · doi:10.1017/s1041610209990354 · Cited by 218 · cited 1× · see citing works
“Furthermore, some systematic reviews suggested that pharmacological therapies are not particularly effective for management of neuropsychiatric symptoms of dementia (Sink et al., 2005, Rodda et al., 2009).”
BackgroundThe Clinician Interview‐ Based Impression (CIBI)
Knopman, D. S., Knapp, M. J., Gracon, S. I., & Davis, C. S. (1994) · Neurology · doi:10.1212/wnl.44.12.2315 · Cited by 213 · cited 2× · see citing works
“, 1994), (3) Clinician’s Interview-Based Impression of Change scale plus caregiver’s input (CIBIC+; Knopman et al., 1994) and (4) Clinical Global Impression of Change (CGIC; Schneider et al.”
BackgroundGalantamine: a randomized, double‐blind, dose comparison in patients with Alzheimer's disease
Wilkinson, D. G., & Murray, J. (2001) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.409 · Cited by 212 · see citing works
Santo, S. G. D., Prinelli, F., Adorni, F., Caltagirone, C., & Musicco, M. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-122140 · Cited by 178 · cited 2× · see citing works
“Although a previous meta-analysis Di Santo et al. (2013) documented no relationship between severity of dementia and efficacy # 2015 The Authors.”
BackgroundMethodHomma, A., Takeda, M., Imai, Y., Udaka, F., Hasegawa, K., Kameyama, M., & Nishimura, T. (2000) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000017259 · Cited by 177 · see citing works
Wilkinson, D. G., Passmore, A. P., Bullock, R. M., Hopker, S. W., Smith, R. C., Potocnik, F. C. V., Maud, C., Engelbrecht, I., Hock, C., Ieni, J. R., et al. (2002) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2002.tb11294.x · Cited by 158 · see citing works
Placebo Response in Antipsychotic Clinical Trials
Rutherford, B. R., Pott, E., Tandler, J. M., Wall, M. M., Roose, S. P., & Lieberman, J. A. (2014) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.1319 · Cited by 152 · cited 1× · see citing works
“Increasing placebo effects over time were found in antipsychotic and antidepressant trials (Walsh et al., 2002; Rutherford et al., 2014).”
BackgroundWang, J., Yu, J., Wang, H.-F., Meng, X., Wang, C., Tan, C., & Tan, L. (2014) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2014-308112 · Cited by 151 · cited 4× · see citing works
“This should strengthen the findings from our analysis over previous meta-analyses (Trinh et al., 2003; Birks, 2006; Hansen et al., 2008; Lockhart et al., 2011;Tan et al., 2014; Wang et al., 2014).”
BackgroundResultInfluentialGalantamine Prolonged-Release Formulation in the Treatment of Mild to Moderate Alzheimer’s Disease
Brodaty, H., Corey‐Bloom, J., Potocnik, F. C. V., Truyen, L., Gold, M., & Damaraju, C. V. (2005) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000086613 · Cited by 122 · see citing works
Feldman, H., Lane, R. M., & on behalf of the Study 304 Group (2007) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2006.099424 · Cited by 107 · see citing works
SB-742457 and donepezil in Alzheimer disease: a randomized, placebo-controlled study
Maher‐Edwards, G., Dixon, R., Hunter, J. A., Gold, M., Hopton, G., Jacobs, G., Hunter, J., & Williams, P. M. (2010) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2562 · Cited by 105 · see citing works
Forette, F., Anand, R., & Gharabawi, G. (1999) · European Journal of Neurology · doi:10.1046/j.1468-1331.1999.640423.x · Cited by 99 · see citing works
A Randomized Study of H3 Antagonist ABT-288 in Mild-To-Moderate Alzheimer's Dementia1
Haig, G. M., Pritchett, Y., Meier, A., Othman, A. A., Hall, C. M., Gault, L. M., & Lenz, R. A. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-140291 · Cited by 71 · see citing works
Hashimoto, M., Yatabe, Y., Ishikawa, T., Fukuhara, R., Kaneda, K., Honda, K., Yuki, S., Ogawa, Y., Imamura, T., Kazui, H., et al. (2015) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000381800 · Cited by 63 · cited 1× · see citing works
“Indeed, a recent study demonstrated that NPI total score significantly increased with dementia stage in patients with AD (Hashimoto et al., 2015).”
BackgroundCumbo, E., & Ligori, L. D. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-131190 · Cited by 63 · see citing works
Frölich, L., on behalf of the Sirocco Investigators, Ashwood, T. J., Nilsson, J., & Eckerwall, G. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-101554 · Cited by 59 · see citing works
Nakamura, Y., Imai, Y., Shigeta, M., Graf, A., Shirahase, T., Kim, H., Fujii, A., Mori, J., & Homma, A. (2011) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000328929 · Cited by 50 · see citing works
Trinh, N.-H., Hoblyn, J., Mohanty, S., & Yaffe, K. (2003) · JAMA · doi:10.1001/jama.289.2.210 · Cited by 37 · cited 3× · see citing works
“This should strengthen the findings from our analysis over previous meta-analyses (Trinh et al., 2003; Birks, 2006; Hansen et al., 2008; Lockhart et al., 2011;Tan et al., 2014; Wang et al., 2014).”
BackgroundResultLockhart, I., Orme, M. E., & Mitchell, S. A. (2011) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000330032 · Cited by 33 · cited 2× · see citing works
“This should strengthen the findings from our analysis over previous meta-analyses (Trinh et al., 2003; Birks, 2006; Hansen et al., 2008; Lockhart et al., 2011;Tan et al., 2014; Wang et al., 2014).”
Result
Flagged first, then by citations
1 of the 49 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Rabins PV, Blacker D, Rovner BW, et al. 2007 American Psychiatric Association practice guideline for the treatment of patients with Alzheimer's disease and other dementias. Second edition. Am J Psychiatry 164: 5– 56. 18340692
Cited by
Sorted by citations
The “rights” of precision drug development for Alzheimer’s disease
Cummings, J. L., Feldman, H., & Scheltens, P. (2019) · Alzheimer s Research & Therapy · doi:10.1186/s13195-019-0529-5 · Cited by 240 · see citing works
Singh, B., Day, C. M., Abdella, S., & Garg, S. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.01.047 · Cited by 245 · see citing works
An update on the safety of current therapies for Alzheimer’s disease: focus on rivastigmine
Khoury, R., Rajamanickam, J., & Grossberg, G. T. (2018) · Therapeutic Advances in Drug Safety · doi:10.1177/2042098617750555 · Cited by 156 · see citing works
Nobis, L., & Masud Husain, B. (2017) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2017.12.007 · Cited by 139 · see citing works
“Two reviews found either no [35], or only slight [37] evidence for a beneficial effect of ChIs compared to placebo, although treatment duration rarely exceeded 24 weeks.”
BackgroundIn Vitro and in Vivo Biological Investigations of Camphene and Its Mechanism Insights: A Review
Hachlafi, N. E., Aanniz, T., Menyiy, N. E., Baaboua, A. E., Omari, N. E., Balahbib, A., Shariati, M. A., Zengin, G., Fikri-Benbrahim, K., & Bouyahya, A. (2021) · Food Reviews International · doi:10.1080/87559129.2021.1936007 · Cited by 128 · see citing works
Magierski, R., Sobów, T., Schwertner, E., & Religa, D. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.01168 · Cited by 121 · see citing works
Kabir, M. T., Uddin, M. S., Begum, M. M., Thangapandiyan, S., Rahman, M. S., Aleya, L., Mathew, B., Ahmed, M., Barreto, G. E., & Ashraf, G. M. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666191008103141 · Cited by 119 · see citing works
Pless, A., Ware, D., Saggu, S., Rehman, H., Morgan, J. C., & Wang, Q. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1263771 · Cited by 98 · see citing works
Pérez, M., Burgos‐Alonso, N., Torrecilla, M., Marco‐Contelles, J., & Bruzos-Cidón, C. (2021) · Biomedicines · doi:10.3390/biomedicines9111689 · Cited by 110 · see citing works
Mehla, J., Gupta, P., Pahuja, M., Diwan, D., & Diksha, D. (2020) · Brain Sciences · doi:10.3390/brainsci10120964 · Cited by 108 · see citing works
Clinical practice guidelines for management of dementia
Shaji, K., Sivakumar, P. T., Rao, G., & Paul, N. (2018) · Indian Journal of Psychiatry · doi:10.4103/0019-5545.224472 · Cited by 104 · see citing works
Ray, S., Das, B. C., & Dasgupta, S. (2019) · Neural Regeneration Research · doi:10.4103/1673-5374.259604 · Cited by 90 · see citing works
“But these medications show side effects such as nausea, vomiting, appetite loss, and increased rate of bowel movements (Kobayashi et al., 2016).”
BackgroundRivastigmine modifies the α-secretase pathway and potentially early Alzheimer’s disease
Ray, B., Maloney, B., Sambamurti, K., Karnati, H. K., Nelson, P. T., Greig, N. H., & Lahiri, D. K. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0709-x · Cited by 91 · see citing works
Wauters, L., Croot, K., Dial, H. R., Duffy, J. R., Grasso, S. M., Kim, E., Schaffer, K. M., Ballard, K. J., Clark, H. M., Kohley, L., et al. (2023) · Neuropsychology Review · doi:10.1007/s11065-023-09607-1 · Cited by 79 · see citing works
“…for Alzheimer’s disease may improve function in some persons with logopenic PPA or other PPA/PPAOS syndromes associated with Alzheimer pathology (Kobayashi et al., 2016; Trinh et al., 2003), and some selective serotonin reuptake inhibitors (SSRIs) can improve behavior in PPA syndromes…”
Curcumin: A Golden Approach to Healthy Aging: A Systematic Review of the Evidence
Nunes, Y. C., Mendes, N. M., de Lima, E. P., Chehadi, A. C., Lamas, C. B., Haber, J., Bueno, M. D. S., Araújo, A., Catharin, V. C. S., Detregiachi, C. R. P., et al. (2024) · Nutrients · doi:10.3390/nu16162721 · Cited by 63 · see citing works
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 · see citing works
Wang, Y., Yu, S., Xue, H., Li, Y., Zhao, C., & Jin, Y. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00098 · Cited by 57 · see citing works
The Efficacy and Safety of Alzheimer’s Disease Therapies: An Updated Umbrella Review
Fan, F., Liu, H., Shi, X., Ai, Y., Liu, Q., & Cheng, Y. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-215423 · Cited by 54 · see citing works
Thancharoen, O., Limwattananon, C., Waleekhachonloet, O., Rattanachotphanit, T., Limwattananon, P., & Limpawattana, P. (2019) · Drugs & Aging · doi:10.1007/s40266-019-00648-x · Cited by 55 · see citing works
Pharmacotherapy of Alzheimer’s disease: an overview of systematic reviews
Majidazar, R., Rezazadeh‐Gavgani, E., Sadigh‐Eteghad, S., & Naseri, A. (2022) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-022-03363-6 · Cited by 52 · see citing works
“Similar cognitive efficacy was found for ChEIs in mild to moderate AD [18].”
BackgroundMartins, M. M., Branco, P. S., & Ferreira, L. M. (2023) · ChemistrySelect · doi:10.1002/slct.202300461 · Cited by 45 · see citing works
Bupropion for the Treatment of Apathy in Alzheimer Disease
Maier, F., Spottke, A., Bach, J., Bartels, C., Buerger, K., Dodel, R., Fellgiebel, A., Fliessbach, K., Frölich, L., Hausner, L., et al. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2020.6027 · Cited by 44 · see citing works
Alzheimer’s Disease: Efficacy of Mono- and Combination Therapy. A Systematic Review
Knorz, A. L., & Quante, A. (2021) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/08919887211044746 · Cited by 43 · see citing works
“At least in mild-to-moderate AD patients, a Bayesian Network meta-analysis from 2016 could not confirm the benefit of ChEI on NPS over placebo.(20) However, other meta-analyses, which also included patients with severe AD, have indeed shown effects of ChEI treatment on NPS over placebo.”
ResultLiu, H., & Jin, B. (2019) · Neural Regeneration Research · doi:10.4103/1673-5374.249228 · Cited by 44 · see citing works
“The cholinergic deficit hypothesis has been a crucial therapy target for Alzheimer’s disease, and the efficacy of cholinesterase inhibitors such as donepezil, galantamine, rivastigmine, has been acknowledged (Kobayashi et al., 2016; Aufschnaiter et al., 2017; Tricco et al., 2018).”
BackgroundWu, J., Kou, X., Ju, H., Zhang, H., Yang, A., & Shen, R. (2021) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2021.128316 · Cited by 42 · see citing works
Zuliani, G., Zuin, M., Romagnoli, T., Polastri, M., Cervellati, C., & Brombo, G. (2024) · Aging Clinical and Experimental Research · doi:10.1007/s40520-023-02675-6 · Cited by 41 · see citing works
“The first, published by Kobayashi et al. in 2015, based on a Bayesian network meta-analysis, evaluate the safety and efficacy of AChEIs in patients with mild-to-moderate AD [10].”
BackgroundGao, Y., Liu, Y., & Li, Y. (2024) · Advances in Clinical and Experimental Medicine · doi:10.17219/acem/176051 · Cited by 38 · see citing works
Cutillas, A., Carrasco, A., Martinez‐Gutierrez, R., Pérez‐Ruiz, T., & Tudela, J. (2017) · Molecules · doi:10.3390/molecules22081382 · Cited by 37 · see citing works
“As well as this bioactivity, SlEO shows acetylcholinesterase (AChE) inhibitory activity [6,9,11,33], so it can be used as memory enhancer in Alzheimer’s disease [34,35].”
Tan, E. C. K., Johnell, K., Bell, J. S., Ptacek, S. G., Fastbom, J., Nordström, P., & Eriksdotter, M. (2019) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2019.06.008 · Cited by 34 · see citing works
Rawat, K., Tewari, D., Bisht, A., Chandra, S., Tiruneh, Y. K., Hassan, H. M., Al‐Emam, A., Sindi, E. R., & Al-Dies, A.-A. M. (2024) · Scientific Reports · doi:10.1038/s41598-024-81285-2 · Cited by 29 · see citing works
Mørk, A., Russell, R. V., de Jong, I. E. M., & Smagin, G. N. (2017) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2017.02.010 · Cited by 27 · see citing works
Vafadarnejad, F., Karimpour‐Razkenari, E., Sameem, B., Saeedi, M., Firuzi, O., Edraki, N., Mahdavi, M. R., & Akbarzadeh, T. (2019) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2019.103192 · Cited by 27 · see citing works
“noted that the efficacy of ChEIs for neuropsychiatric symptoms is not definitely accepted in patients with mild‐to‐moderate AD [16].”
BackgroundNakagawa, R., Ohnishi, T., Kobayashi, H., Yamaoka, T., Yajima, T., Tanimura, A., Kato, T., & Yoshizawa, K. (2017) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s133145 · Cited by 26 · see citing works
“24 These results suggest that there may have been possible overestimation of the speed of cognitive decline based on Mendiondo’s model in the present study.”
Fisher, A., Carney, G., Bassett, K. L., & Dormuth, C. R. (2017) · Drugs & Aging · doi:10.1007/s40266-017-0438-x · Cited by 25 · see citing works
Koo, G. K., Gaur, A., Tumati, S., Kusumo, R. W., Bawa, K. K., Herrmann, N., Gallagher, D., & Lanctôt, K. L. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105047 · Cited by 25 · see citing works
Kronhaus, A. K., Fuller, S., Zimmerman, S. I., & Reed, D. (2016) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2016.04.028 · Cited by 23 · see citing works
Zarini-Gakiye, E., Amini, J., Sanadgol, N., Vaezi, G., & Kazem, P. (2020) · Current Molecular Pharmacology · doi:10.2174/1874467213666200422090135 · Cited by 22 · see citing works
The Effects of Curcumin on Neurodegenerative Diseases: a Systematic Review
Bássoli, R. M. F., Audi, D., Ramalho, B. J., Audi, M., Quesada, K. R., & Barbalho, S. M. (2023) · Journal of Herbal Medicine · doi:10.1016/j.hermed.2023.100771 · Cited by 21 · see citing works
Effects of New Galantamine Derivatives in a Scopolamine Model of Dementia in Mice
Lazarova, M. I., Tancheva, L. P., Alexandrova, A., Tsvetanova, E. R., Georgieva, A. P., Stefanova, M. O., Tsekova, D. S., Vezenkov, L. T., Kalfin, R. E., Uzunova, D. N., et al. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-215165 · Cited by 20 · see citing works
Hazen, J., Vistnes, M., Barca, M. L., Eldholm, R. S., Persson, K., Brækhus, A., Saltvedt, I. T., Selbæk, G., Engedal, K., & Knapskog, A. (2019) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000342 · Cited by 20 · see citing works
Liang, J., Li, J., Jia, R., Wang, Y., Wu, R.-K., Zhang, H., Hang, L., & Xu, Y. (2018) · Clinical Interventions in Aging · doi:10.2147/cia.s184968 · Cited by 19 · see citing works
“Our results showed the consistency with previous research 43 that the efficacy of galantamine is greater than that of rivastigmine followed by donepezil, but it should be noted that some studies indicated that these three drugs have no significant difference in improving the cognitive function of…”
Sheikh, M., & Ammar, M. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1398952 · Cited by 23 · see citing works
Acetylcholinesterase inhibitors (Galantamine, Rivastigmine, and Donepezil)
Sridhar, G. R. (2021) · Springer eBooks · doi:10.1007/978-3-319-56015-1_418-1 · Cited by 17 · see citing works
Is there an alternative to quality-adjusted life years for supporting healthcare decision making?
Béresniak, A., & Dupont, D. (2016) · Expert Review of Pharmacoeconomics & Outcomes Research · doi:10.1080/14737167.2016.1184975 · Cited by 15 · see citing works
Acetylcholinesterase inhibitors (Galantamine, Rivastigmine, and Donepezil)
Sridhar, G. R. (2022) · Springer eBooks · doi:10.1007/978-3-030-62059-2_418 · Cited by 14 · see citing works
Vila‐Castelar, C., Ly, J. J., Kaplan, L. R., Dyk, K. V., Berger, J. T., Macina, L. O., Stewart, J. L., & Foldi, N. S. (2018) · Archives of Clinical Neuropsychology · doi:10.1093/arclin/acy032 · Cited by 14 · see citing works
Liu, C. S., Herrmann, N., Song, B. X., Ba, J., Gallagher, D., OH, P. I., Marzolini, S., Rajji, T. K., Charles, J., Papneja, P., et al. (2021) · BMC Geriatrics · doi:10.1186/s12877-021-02636-6 · Cited by 14 · see citing works
Ueda, K., Katayama, S., Arai, T., Furuta, N., Ikebe, S.-I., Ishida, Y., Kanaya, K., Ouma, S., Sakurai, H., Sugitani, M., et al. (2019) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000501364 · Cited by 14 · see citing works
Oliveira, L. D. F., Camargos, E. F., Louzada, L. L., Machado, F. V., & Novaes, M. R. C. G. (2020) · Psychiatry Research · doi:10.1016/j.psychres.2020.113591 · Cited by 11 · see citing works
Apathy Associated with Alzheimer's Disease
Wu, D., Zhang, B., Chang, Y., & Huang, S.-M. (2024) · Current Alzheimer Research · doi:10.2174/0115672050350970241216072400 · Cited by 10 · see citing works
“ChIs can moderately improve the overall cognitive function of AD patients [83], however, they have not yet been proven to be effective in the long-term treat-ment of apathy in AD.”
Iketani, R., Ohno, K., Kawasaki, Y., Matsumoto, K., Yamada, H., & Kishino, S. (2018) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b17-00929 · Cited by 10 · see citing works
Managing the Behavioral and Psychological Symptoms of Dementia
Mendez, M. F. (2022) · Current Treatment Options in Neurology · doi:10.1007/s11940-022-00715-6 · Cited by 9 · see citing works
Morte, A., Vaqué, A., Iniesta, M., Schug, B. S., Koch, C., de la Torre, R., & Schurad, B. (2022) · European Journal of Drug Metabolism and Pharmacokinetics · doi:10.1007/s13318-022-00778-5 · Cited by 7 · see citing works
Zala, D., Chan, D., & McCrone, P. (2017) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.4745 · Cited by 7 · see citing works
“No recently published meta-analyses (Hansen et al., 2008; Lockhart et al., 2011; Di Santo et al., 2013; Kobayashi et al., 2015) or trials within these satisfied the conditions for a treatment effect for donepezil on the ADCS-ADL.”
BackgroundAntimuscarinic Cascade Across Individual Cholinesterase Inhibitors in Older Adults with Dementia
Masurkar, P. P., Chatterjee, S., Sherer, J. T., & Aparasu, R. R. (2021) · Drugs & Aging · doi:10.1007/s40266-021-00863-5 · Cited by 7 · see citing works
“Although donepezil is known to have a better safety profile than rivastigmine and galantamine [29], the findings suggest that donepezil is more likely to lead to antimuscarinic cascade than rivastigmine.”
BackgroundKumar, C. T. S., Varghese, M., Duddu, V., Vaitheswaran, S., Srivastava, S., Shaji, K., George, S., Singh, N. K., Goyal, N., Bakhla, A. K., et al. (2023) · Indian Journal of Psychiatry · doi:10.4103/indianjpsychiatry.indianjpsychiatry_736_21 · Cited by 6 · see citing works
“[21,22] Medications for dementia Efficacy of AChEI, [23] memantine, [24] and combination therapy of memantine plus donepezil [25] have been established in treatment of patients with dementia.”
Rapid health technology assessment of galantamine for the treatment of Alzheimer’s disease: A review
Xing, B., Yang, J., Hua, H., & Jiang, R. (2025) · Medicine · doi:10.1097/md.0000000000042744 · Cited by 7 · see citing works
“24, 26, 31, 32 ] Thancharoen et al reported that galantamine treatment significantly significantly improved the behavioral symptoms compared with the placebo and treatment with donepezil and rivastigmine ( SMD”
Procter, N. G., Hamer, H. P., McGarry, D. E., Wilson, R. L., & Froggatt, T. (2018) · Cambridge University Press eBooks · doi:10.1017/9781316718278 · Cited by 6 · see citing works
Chau, S. A., Liu, C. S., Ruthirakuhan, M. T., Lanctôt, K. L., & Herrmann, N. (2017) · Mental health and illness worldwide · doi:10.1007/978-981-10-2414-6_20 · Cited by 7 · see citing works
Bhosale, S. S., Sivakkumar, S., Jamadagni, S. B., & Arulmozhi, S. (2024) · Research Journal of Pharmacy and Technology · doi:10.52711/0974-360x.2024.00086 · Cited by 5 · see citing works
Treatment of Vascular and Neurodegenerative Forms of Cognitive Impairment and Dementias
Perlett, L., & Smith, E. E. (2022) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2022.07.008 · Cited by 5 · see citing works
The efficacy of donepezil for the treatment of Alzheimer’s disease
Warren, S. L., & Moustafa, A. A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821334-6.00001-6 · Cited by 5 · see citing works
Georgiou, E. E. Z., Politis, A. M., Kosmidis, M. H., Yannakoulia, M., Dardiotis, E., Hadjigeorgiou, G. M., Sakka, P., Scarmeas, N., Εconomou, P., & Alexopoulos, P. (2023) · International Journal of Psychiatry in Clinical Practice · doi:10.1080/13651501.2023.2296889 · Cited by 4 · see citing works
Chau, S. A., Liu, C. S., Ruthirakuhan, M. T., Lanctôt, K. L., & Herrmann, N. (2016) · Mental health and illness worldwide · doi:10.1007/978-981-10-0370-7_20-1 · Cited by 4 · see citing works
“In a Bayesian network meta-analysis of 21 studies, the efficacy and tolerability of ChEIs in the treatment of mild-to-moderate AD were investigated (Kobayashi et al. 2015).”
MethodBoongird, C., Tearneukit, W., Wongpipathpong, W., McKay, G. J., & Thakkinstian, A. (2022) · Medicine · doi:10.1097/md.0000000000032382 · Cited by 4 · see citing works
Combination Drug Therapy for the Management of Alzheimer’s Disease
Dudchenko, N. G., & Mkhitaryan, E. A. (2024) · Russian Journal of Geriatric Medicine · doi:10.37586/2686-8636-2-2024-140-144 · Cited by 2 · see citing works
Boongird, C., Anothaisintawee, T., Tearneukit, W., Wongpipathpong, W., Suthutvoravut, U., Thongpan, M., Pongsettakul, N., Attia, J., McKay, G. J., Rattanasiri, S., et al. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251378354 · Cited by 2 · see citing works
Zuliani, G., Cervellati, C., Zuin, M., & Brombo, G. (2026) · Aging Clinical and Experimental Research · doi:10.1007/s40520-026-03353-z · Cited by 1 · see citing works
Real‐world evidence for amyloid‐targeted therapies: Lecanemab and donanemab
Hakim, R., Harris, K., Merrill, L., Falk‐Vargas, A., Whalen, E., Xia, T., Ochoa, O., Hunter, D., & Schulz, P. E. (2026) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.70404 · Cited by 2 · see citing works
Central Nervous System Stimulants and Drugs That Suppress Appetite
Bello, N. T., & Zahner, M. R. (2017) · Side effects of drugs annual · doi:10.1016/bs.seda.2017.07.007
Препарати — інгібітори холінестерази в терапії деменцій: клініко-фармакологічні аспекти
Burchynskyi, S. H., Raichenko, K. V., & Gushcha, V. V. (2018) · INTERNATIONAL NEUROLOGICAL JOURNAL · doi:10.22141/2224-0713.2.96.2018.130483
Vila‐Castelar, C. (2018) · CUNY Academic Works (City University of New York)
Dunne, R. A., & Burns, A. S. (2020) · Cambridge University Press eBooks · doi:10.1017/9781911623465.016
Boongird, C., Tearneukit, W., Anothaisintawee, T., McKay, G. J., & Thakkinstian, A. (2021) · Research Square · doi:10.21203/rs.3.rs-940193/v1
Schaffer, K. M., & Henry, M. L. (2024) · Elsevier eBooks · doi:10.1016/b978-0-12-820480-1.00125-x
Gibfried, M., & Grossberg, G. T. (2024) · Cambridge University Press eBooks · doi:10.1017/9781108630344.009
Determination of Enzyme Inhibitory and Antioxidant Activities of Selected Oak Galls
Haşimi, N., Abdioğlu, M. D., & Boğa, M. (2025) · Bitlis Eren Üniversitesi Fen Bilimleri Dergisi · doi:10.17798/bitlisfen.1669087
Wu, Y., Di, Y., Wang, H. W., Wang, L., Zhang, J., Zhang, Y., & Lyu, D. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103216
Shaik, N. S., Balya, H., Ramamurthy, S., Pandiyan, B., Mart, E. J., & Gunturu, S. L. (2026) · Dementia & Neuropsychologia · doi:10.1590/1980-5764-dn-2025-0472
- Authors
- Kobayashi, H., Ohnishi, T., Nakagawa, R., & Yoshizawa, K.
- Affiliations
- Janssen Pharmaceutical K.K. (Japan) (JP)
- Corresponding author
- Ohnishi, Takashi
- Venue
- International Journal of Geriatric Psychiatry
- Publisher
- Wiley
- Published
- 2015-12-17
- Volume
- 31
- Issue
- 8
- Pages
- 892-904
- ISSN
- 0885-6230 (ISSN-L)
- 1099-1166
- PMC
- PMC6084309
- OpenAlex
- W2197001618
- Cited by
- 79
- References
- 49
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 11 · 2023: 7 · 2022: 6 · 2021: 11 · 2020: 8 · 2019: 9 · 2018: 8 · 2017: 8 · 2016: 3
- FWCI
- 0.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- International Journal of Geriatric Psychiatry (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Janssen Pharmaceutical K.K. of Johnson & Johnson
- Topics
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- cholinesterase inhibitors, Alzheimer's disease, donepezil, galantamine, rivastigmine, cognitive function, neuropsychiatric symptoms, treatment efficacy, drug safety, adverse events, mild to moderate dementia
- MeSH terms
- Rivastigmine, Network Meta-Analysis, Donepezil, Aged, Alzheimer Disease, Bayes Theorem, Cholinesterase Inhibitors, Cognition, Female, Galantamine, Humans, Indans, Male, Middle Aged, Piperidines, Randomized Controlled Trials as Topic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
