1. Deture, MA, Dickson, DW. The neuropathological diagnosis of Alzheimer’s disease. Mol Neurodegen. 2019;14(1):32. doi:10.1186/s13024-019-0333-5
Google Scholar | Crossref | Medline2. Esiri, MM, Chance, SA. Cognitive reserve, cortical plasticity and resistance to Alzheimer’s disease. Alzheimers Res Ther. 2012;4(2):7. doi:10.1186/alzrt105
Google Scholar | Crossref | Medline3. Alzheimer’s Association . 2020 Alzheimer’s disease facts and figures. Alzheimers Dement. 2020;10. doi:10.1002/alz.12068
Google Scholar4. Masters, CL, Bateman, R, Blennow, K, Rowe, CC, Sperling, RA, Cummings, JL. Alzheimer’s disease. Nat Rev Dis Primers. 2015;1:15056. doi:10.1038/nrdp.2015.56
Google Scholar | Crossref | Medline5. Fessel, WJ . Concordance of several subcellular interactions initiates Alzheimer’s dementia: their reversal requires combination treatment. Am J Alzheimers Dis Other Demen. 2017;32(3):166–181. doi:10.1177/1533317517698790
Google Scholar | SAGE Journals | ISI6. Kisby, B, Jarrell, JT, Agar, ME, et al. Alzheimer’s disease and its potential alternative therapeutics. J Alzheimers Dis Parkinsonism. 2019;9(5):477. doi:10.4172/2161-0460.1000477
Google Scholar | Medline7. Food and Drug Administration (FDA) . FDA news release: FDA grants accelerated approval for Alzheimer’s drug. Published June 7, 2021. Accessed July 5, 2021. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-drug
Google Scholar8. Birks, J . Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev. 2006;(1):CD005593. doi:10.1002/14651858.CD005593
Google Scholar | Medline | ISI9. Birks, JS, Harvey, RJ. Donepezil for dementia due to Alzheimer’s disease. Cochrane Database Syst Rev. 2018;6(6):CD001190. doi:10.1002/14651858.CD001190.pub3
Google Scholar | Medline10. Loy, C, Schneider, L. Galantamine for Alzheimer’s disease. Cochrane Database Syst Rev. 2006;(1):CD001747. doi:10.1002/14651858.CD001747.pub2
Google Scholar | Medline11. Birks, JS, Grimley Evans, J. Rivastigmine for Alzheimer’s disease. Cochrane Database Syst Rev. 2015;(4):CD001191. doi:10.1002/14651858.CD001191.pub3
Google Scholar12. Dubois, B, Chupin, M, Hampel, H, et al. Donepezil decreases annual rate of hippocampal atrophy in suspected prodromal Alzheimer’s disease. Alzheimers Dement. 2015;11(9):1041–1049. doi:10.1016/j.jalz.2014.10.003
Google Scholar | Crossref | Medline | ISI13. Cavedo, E, Grothe, MJ, Colliot, O, et al. Reduced basal forebrain atrophy progression in a randomized donepezil trial in prodromal Alzheimer’s disease. Sci Rep. 2017;7(1):11706. doi:10.1038/s41598-017-09780-3
Google Scholar | Crossref | Medline14. Krishnan, KR, Charles, HC, Doraiswamy, PM, et al. Randomized, placebo-controlled trial of the effects of donepezil on neuronal markers and hippocampal volumes in Alzheimer’s disease. Am J Psychiatry. 2003;160(11):2003–2011. doi:10.1176/appi.ajp.160.11.2003.
Google Scholar | Crossref | Medline | ISI15. Hashimoto, M, Kazui, H, Matsumoto, K, Nakano, Y, Yasuda, M, Mori, E. Does donepezil treatment slow the progression of hippocampal atrophy in patients with Alzheimer’s disease? Am J Psychiatry. 2005;162(4):676–682. doi:10.1176/appi.ajp.162.4.676
Google Scholar | Crossref | Medline | ISI16. Hampel, H, Mesulam, MM, Cuello, AC, et al. The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease. Brain. 2018;141(7):1917–1933. doi:10.1093/brain/awy132
Google Scholar | Crossref | Medline17. Drago, V, Babiloni, C, Bartrés-Faz, D, et al. Disease tracking markers for Alzheimer’s disease at the prodromal (MCI) stage. J Alzheimers Dis. 2011;26(Suppl 3):159–199. doi:10.3233/JAD-2011-0043
Google Scholar | Crossref | Medline18. Fellgiebel, A, Yakushev, I. Diffusion tensor imaging of the hippocampus in MCI and early Alzheimer’s disease. J Alzheimers Dis. 2011;26(Suppl 3):257–262. doi:10.3233/JAD-2011-0001
Google Scholar | Crossref | Medline19. Jack, CR, Vemuri, P, Wiste, HJ, et al. Evidence for ordering of Alzheimer disease biomarkers. Arch Neurol. 2011;68(12):1526–1535. doi:10.1001/archneurol.2011.183
Google Scholar | Crossref | Medline20. Kobayashi, H, Ohnishi, T, Nakagawa, R, Yoshizawa, K. The comparative efficacy and safety of cholinesterase inhibitors in patients with mild-to-moderate Alzheimer’s disease: a Bayesian network meta-analysis. Int J Geriatr Psychiatry. 2016;31(8):892–904. doi:10.1002/gps.4405
Google Scholar | Crossref | Medline21. Campbell, N, Ayub, A, Boustani, MA, et al. Impact of cholinesterase inhibitors on behavioral and psychological symptoms of Alzheimer’s disease: a meta-analysis. Clin Interv Aging. 2008;3(4):719–728. doi:10.2147/cia.s4250
Google Scholar | Medline | ISI22. Lockhart, IA, Orme, ME, Mitchell, SA. The efficacy of licensed-indication use of donepezil and memantine monotherapies for treating behavioural and psychological symptoms of dementia in patients with Alzheimer’s disease: systematic review and meta-analysis. Dement Geriatr Cogn Dis Extra. 2011;1(1):212–227. doi:10.1159/000330032
Google Scholar | Crossref | Medline23. McShane, R, Westby, MJ, Roberts, E, et al. Memantine for dementia. Cochrane Database Syst Rev. 2019;3(3):CD003154. doi:10.1002/14651858.CD003154.pub6
Google Scholar | Medline24. Weiner, MW, Sadowsky, C, Saxton, J, et al. Magnetic resonance imaging and neuropsychological results from a trial of memantine in Alzheimer’s disease. Alzheimers Dement. 2011;7(4):425–435. doi:10.1016/j.jalz.2010.09.003
Google Scholar | Crossref | Medline25. Parsons, CG, Danysz, W, Dekundy, A, Pulte, I. Memantine and cholinesterase inhibitors: complementary mechanisms in the treatment of Alzheimer’s disease. Neurotox Res. 2013;24(3):358–369. doi:10.1007/s12640-013-9398-z
Google Scholar | Crossref | Medline | ISI26. Periclou, AP, Ventura, D, Sherman, T, et al. Lack of pharmacokinetic or pharmacodynamic interaction between memantine and donepezil. Ann Pharmacother. 2004;38(9):1389–1394. doi:10.1345/aph.1D638
Google Scholar | SAGE Journals | ISI27. National Institute for Health and Care Excellence (NICE) . Dementia: assessment, management and support for people living with dementia and their carers (NG97). NICE. Published June 20, 2018. Accessed July 15, 2020. https://www.nice.org.uk/guidance/ng97/chapter/Recommendations#pharmacological-interventions-for-dementia
Google Scholar28. Matsuzono, K, Hishikawa, N, Ohta, Y, et al. Combination therapy of cholinesterase inhibitor (donepezil or galantamine) plus memantine in the okayama memantine study. J Alzheimers Dis. 2015;45(3):771–780. doi:10.3233/JAD-143084
Google Scholar | Crossref | Medline29. Green, KN, Khashwji, H, Estrada, T, Laferla, FM. ST101 induces a novel 17 kDa APP cleavage that precludes Aβ generation in vivo. Ann Neurol. 2011;69(5):831–844. doi:10.1002/ana.22325
Google Scholar | Crossref | Medline30. Jadad, AR, Moore, RA, Carroll, D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17(1):1–12. doi:10.1016/0197-2456(95)00134-4
Google Scholar | Crossref | Medline31. Moher, D, Shamseer, L, Clarke, M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4(1):1. doi:10.1186/2046-4053-4-1
Google Scholar | Crossref | Medline32. Araki, T, Wake, R, Miyaoka, T, et al. The effects of combine treatment of memantine and donepezil on Alzheimer’s disease patients and its relationship with cerebral blood flow in the prefrontal area. Int J Geriatr Psychiatry. 2014;29(9):881–889. doi:10.1002/gps.4074
Google Scholar | Crossref | Medline33. Howard, R, McShane, R, Lindesay, J, et al. Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N Engl J Med. 2012;366(10):893–903. doi:10.1056/NEJMoa1106668
Google Scholar | Crossref | Medline | ISI34. Doody, RS, Geldmacher, DS, Farlow, MR, et al. Efficacy and safety of donepezil 23 mg versus donepezil 10 mg for moderate-to-severe Alzheimer’s disease: a subgroup analysis in patients already taking or not taking concomitant memantine. Dement Geriatr Cogn Disord. 2012;33(2-3):164–173. doi:10.1159/000338236
Google Scholar | Crossref | Medline35. Tariot, PN, Farlow, MR, Grossberg, GT, et al. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA. 2004;291(3):317–324. doi:10.1001/jama.291.3.317
Google Scholar | Crossref | Medline | ISI36. Peters, O, Fuentes, M, Joachim, LK, et al. Combined treatment with memantine and galantamine-CR compared with galantamine-CR only in antidementia drug naïve patients with mild-to-moderate Alzheimer’s disease. Alzheimers Dement (N Y). 2015;1(3):198–204. doi:10.1016/j.trci.2015.10.001
Google Scholar | Crossref | Medline37. Peters, O, Lorenz, D, Fesche, A, et al. A combination of galantamine and memantine modifies cognitive function in subjects with amnestic MCI. J Nutr Health Aging. 2012;16(6):544–548. doi:10.1007/s12603-012-0062-8
Google Scholar | Crossref | Medline38. Choi, SH, Park, KW, Na, DL, et al. Tolerability and efficacy of memantine add-on therapy to rivastigmine transdermal patches in mild to moderate Alzheimer’s disease: a multicenter, randomized, open-label, parallel-group study. Curr Med Res Opin. 2011;27(7):1375–1383. doi:10.1185/03007995.2011.582484
Google Scholar | Crossref | Medline39. Grossberg, GT, Manes, F, Allegri, RF, et al. The safety, tolerability, and efficacy of once-daily memantine (28 mg): a multinational, randomized, double-blind, placebo-controlled trial in patients with moderate-to-severe Alzheimer’s disease taking cholinesterase inhibitors. CNS Drugs. 2013;27(6):469–478. doi:10.1007/s40263-013-0077-7
Google Scholar | Crossref | Medline40. Porsteinsson, AP, Grossberg, GT, Mintzer, J, Olin, JT. Memantine treatment in patients with mild to moderate Alzheimer’s disease already receiving a cholinesterase inhibitor: a randomized, double-blind, placebo-controlled trial. Curr Alzheimer Res. 2008;5(1):83–89. doi:10.2174/156720508783884576
Google Scholar | Crossref | Medline | ISI41. Cornelli, U . Treatment of Alzheimer’s disease with a cholinesterase inhibitor combined with antioxidants. Neurodegener Dis. 2010;7(1-3):193–202. doi:10.1159/000295663
Google Scholar | Crossref | Medline42. Yancheva, S, Ihl, R, Nikolova, G, et al. Ginkgo biloba extract EGb 761(R), donepezil or both combined in the treatment of Alzheimer’s disease with neuropsychiatric features: a randomised, double-blind, exploratory trial. Aging Ment Health. 2009;13(2):183–190. doi:10.1080/13607860902749057
Google Scholar | Crossref | Medline43. Atri, A, Frölich, L, Ballard, C, et al. Effect of idalopirdine as adjunct to cholinesterase inhibitors on change in cognition in patients with Alzheimer disease: three randomized clinical trials. JAMA. 2018;319(2):130–142. doi:10.1001/jama.2017.20373
Google Scholar | Crossref | Medline44. Gauthier, S, Rountree, S, Finn, B, et al. Effects of the acetylcholine release agent st101 with donepezil in Alzheimer’s disease: a randomized phase 2 study. J Alzheimers Dis. 2015;48(2):473–481. doi:10.3233/JAD-150414
Google Scholar | Crossref | Medline45. Feldman, HH, Doody, RS, Kivipelto, M, et al. Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. Neurology. 2010;74(12):956–964. doi:10.1212/WNL.0b013e3181d6476a
Google Scholar | Crossref | Medline | ISI46. Mowla, A, Mosavinasab, M, Haghshenas, H, Borhani Haghighi, A. Does serotonin augmentation have any effect on cognition and activities of daily living in Alzheimer’s dementia? A double-blind, placebo-controlled clinical trial. J Clin Psychopharmacol. 2007;27(5):484–487.
Google Scholar | Crossref | Medline47. Sun, Y, Lu, CJ, Chien, KL, et al. Efficacy of multivitamin supplementation containing vitamins B6 and B12 and folic acid as adjunctive treatment with a cholinesterase inhibitor in Alzheimer’s disease: a 26-week, randomized, double-blind, placebo-controlled study in Taiwanese patients. Clin Ther. 2007;29(10):2204–2214. doi:10.1016/j.clinthera.2007.10.012
Google Scholar | Crossref | Medline | ISI48. Farlow, MR, Salloway, S, Tariot, PN, et al. Effectiveness and tolerability of high-dose (23 mg/d) versus standard-dose (10 mg/d) donepezil in moderate to severe Alzheimer’s disease: a 24-week, randomized, double-blind study. Clin Ther. 2010;32(7):1234–1251. doi:10.1016/j.clinthera.2010.06.019