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Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Review Article

Combination Therapy for the Treatment of Alzheimer’s Disease: Recent Progress and Future Prospects

Author(s): Ekta Shirbhate, Vijay K. Patel, Priya Tiwari, Rakesh Kore, Ravichandran Veerasamy, Achal Mishra and Harish Rajak*

Volume 22, Issue 22, 2022

Published on: 07 October, 2022

Page: [1849 - 1867] Pages: 19

DOI: 10.2174/1568026622666220907114443

Price: $65

Open Access Journals Promotions 2
Abstract

Background: The management of Alzheimer’s disease is challenging due to its complexity. However, the currently approved and marketed treatments for this neurodegenerative disorder revolves around cholinesterase inhibitors, glutamate regulators, or the combination of these agents. Despite the prompt assurance of many new drugs, several agents were unsuccessful, especially in phase II or III trials, not meeting efficacy endpoints.

Objective: The execution of effective treatment approaches through further trials investigating a rational combination of agents is necessitude for Alzheimer’s disease.

Methods: For this review, more than 248 relevant scientific papers were considered from a variety of databases (Scopus, Web of Science, Google Scholar, ScienceDirect, and PubMed) using the keywords Alzheimer’s disease, amyloid-β, combination therapies, cholinesterase inhibitors, dementia, glutamate regulators, AD hypothesis.

Result and Discussion: The researcher's intent is to either develop a disease-modifying therapeutic means for aiming in the early phases of dementia and/or optimize the available symptomatic treatments principally committed to the more advanced stages of Alzheimer’s. Since Alzheimer's possesses multifactorial pathogenesis, designing a multimodal therapeutic intervention for targeting different pathological processes of dementia may appear to be the most practical method to alter the course of disease progression.

Conclusion: The combination approach may even allow for providing individual agents in lower doses, with reducible costs and side effects. Numerous studies on combination therapy predicted better clinical efficacy than monotherapy. The literature review highlights the major clinical studies (both symptomatic and disease-modifying) conducted in the past decade on combination therapy to combat cognitive disorder.

Keywords: Alzheimer’s disease, Amyloid-β, Combination therapies, Cholinesterase inhibitors, Dementia, Glutamate regulators, AD hypothesis.

Graphical Abstract
[1]
Blennow, K.; De Leon, M.J.; Zetterberg, H. Alzheimer’s disease. Lancet, 2006, 368(9533), 387-403.
[http://dx.doi.org/10.1016/S0140-6736(06)69113-7] [PMID: 16876668]
[2]
Alzheimer’s association. 2021 Alzheimer’s disease facts and figures. Alzheimers Dement., 2021, 17(3), 327-406.
[http://dx.doi.org/10.1002/alz.12328] [PMID: 33756057]
[3]
Tai, S.Y.; Chen, C.H.; Chien, C.Y.; Yang, Y.H. Cilostazol as an add-on therapy for patients with Alzheimer’s disease in Taiwan: A case control study. BMC Neurol., 2017, 17(1), 40.
[http://dx.doi.org/10.1186/s12883-017-0800-y] [PMID: 28231822]
[4]
Burns, A.; Iliffe, S. Alzheimer’s disease. BMJ, 2009, 338(feb05 1), b158.
[http://dx.doi.org/10.1136/bmj.b158] [PMID: 19196745]
[5]
World Health Organization. Dementia. Available from: www. who.int/news-room/fact- sheets/detail/dementia (Accessed on: 11 Feb 2022).
[6]
Amat-ur-Rasool, H.; Ahmed, M.; Hasnain, S.; Carter, W.G. Anti-Cholinesterase combination drug therapy as a potential treatment for Alzheimer’s Disease. Brain Sci., 2021, 11(2), 184.
[http://dx.doi.org/10.3390/brainsci11020184] [PMID: 33540879]
[7]
Selkoe, D.J.; Hardy, J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol. Med., 2016, 8(6), 595-608.
[http://dx.doi.org/10.15252/emmm.201606210] [PMID: 27025652]
[8]
Iqbal, K.; Alonso, A.C.; Chen, S.; Chohan, M.O.; El-Akkad, E.; Gong, C.X.; Khatoon, S.; Li, B.; Liu, F.; Rahman, A.; Tanimukai, H.; Grundke, I.I. Tau pathology in Alzheimer disease and other tauopathies. Biochim. Biophys. Acta, 2005, 1739(2-3), 198-210.
[http://dx.doi.org/10.1016/j.bbadis.2004.09.008] [PMID: 15615638]
[9]
Mufson, E.J.; Counts, S.E.; Perez, S.E.; Ginsberg, S.D. Cholinergic system during the progression of Alzheimer’s disease: Therapeutic implications. Expert Rev. Neurother., 2008, 8(11), 1703-1718.
[http://dx.doi.org/10.1586/14737175.8.11.1703] [PMID: 18986241]
[10]
Uddin, M.S.; Kabir, M.T. Emerging signal regulating potential of genistein against Alzheimer’s disease: A promising molecule of interest. Front. Cell Dev. Biol., 2019, 7, 197.
[http://dx.doi.org/10.3389/fcell.2019.00197] [PMID: 31620438]
[11]
Reitz, C.; Brayne, C.; Mayeux, R. Epidemiology of Alzheimer disease. Nat. Rev. Neurol., 2011, 7(3), 137-152.
[http://dx.doi.org/10.1038/nrneurol.2011.2] [PMID: 21304480]
[12]
Ringman, J.M.; Goate, A.; Masters, C.L.; Cairns, N.J.; Danek, A.; Graff-Radford, N.; Ghetti, B.; Morris, J.C. Genetic heterogeneity in Alzheimer’s disease and implications for treatment strategies. Curr. Neurol. Neurosci. Rep., 2014, 14(11), 499.
[http://dx.doi.org/10.1007/s11910-014-0499-8] [PMID: 25217249]
[13]
Hirtz, D.; Thurman, D.J.; Gwinn, H.K.; Mohamed, M.; Chaudhuri, A.R.; Zalutsky, R. How common are the “common” neurologic disorders? Neurology, 2007, 68(5), 326-337.
[http://dx.doi.org/10.1212/01.wnl.0000252807.38124.a3] [PMID: 17261678]
[14]
Ferri, C.P.; Prince, M.; Brayne, C.; Brodaty, H.; Fratiglioni, L.; Ganguli, M.; Hall, K.; Hasegawa, K.; Hendrie, H.; Huang, Y.; Jorm, A.; Mathers, C.; Menezes, P.R.; Rimmer, E.; Scazufca, M. Global prevalence of dementia: A Delphi consensus study. Lancet, 2005, 366(9503), 2112-2117.
[http://dx.doi.org/10.1016/S0140-6736(05)67889-0] [PMID: 16360788]
[15]
Giordano, M.; Dominguez, L.J.; Vitrano, T.; Curatolo, M.; Ferlisi, A.; Di Prima, A.; Belvedere, M.; Barbagallo, M. Combination of intensive cognitive rehabilitation and donepezil therapy in Alzheimer’s Disease (AD). Arch. Gerontol. Geriatr., 2010, 51(3), 245-249.
[http://dx.doi.org/10.1016/j.archger.2009.11.008] [PMID: 19969381]
[16]
Salloway, S.P.; Sevingy, J.; Budur, K.; Pederson, J.T.; DeMattos, R.B.; Von Rosenstiel, P.; Paez, A.; Evans, R.; Weber, C.J.; Hendrix, J.A.; Worley, S.; Bain, L.J.; Carrillo, M.C. Advancing combination therapy for Alzheimer’s disease. Alzheimers Dement., 2020, 6(1), e12073.
[http://dx.doi.org/10.1002/trc2.12073] [PMID: 33043108]
[17]
Yan, R.; Vassar, R. Targeting the β secretase BACE1 for Alzheimer’s disease therapy. Lancet Neurol., 2014, 13(3), 319-329.
[http://dx.doi.org/10.1016/S1474-4422(13)70276-X] [PMID: 24556009]
[18]
Murphy, M.P.; LeVine, H., III Alzheimer’s disease and the amyloid-β peptide. J. Alzheimers Dis., 2010, 19(1), 311-323.
[http://dx.doi.org/10.3233/JAD-2010-1221] [PMID: 20061647]
[19]
Cummings, J.L.; Tong, G.; Ballard, C. Treatment combinations for Alzheimer’s disease: Current and future pharmacotherapy options. J. Alzheimers Dis., 2019, 67(3), 779-794.
[http://dx.doi.org/10.3233/JAD-180766] [PMID: 30689575]
[20]
Aricept (donepezil hydrochloride). Full Prescribing Information; Eisai Inc.: Woodcliff Lake, NJ, 2015.
[21]
Exelon (rivastigmine tartrate). Full Prescribing Information; Novartis Pharmaceuticals Corporation: East Hanover, NJ, 2015.
[22]
Dailymed. Exelon Patch (rivastigmine transdermal system). Full Prescribing Information; Novartis Pharmaceuticals Corporation: East Hanover, NJ, 2016.
[23]
Dailymed. Razadyne (galantamine hydrobromide); Full Prescribing Information, Janssen Pharmaceuticals Inc.: Titusville, NJ, 2016.
[24]
Dailymed. Namenda XR (memantine hydrochloride). Full Prescribing Information; Forest Pharmaceuticals Inc.: St. Louis, MO, 2014.
[25]
Dailymed. Namzaric (memantine and donepezil hydrochlorides); Full Prescribing Information, Allergan USA, Inc.: Irvine, CA, 2016.
[26]
Bateman, R.J.; Xiong, C.; Benzinger, T.L.S.; Fagan, A.M.; Goate, A.; Fox, N.C.; Marcus, D.S.; Cairns, N.J.; Xie, X.; Blazey, T.M.; Holtzman, D.M.; Santacruz, A.; Buckles, V.; Oliver, A.; Moulder, K.; Aisen, P.S.; Ghetti, B.; Klunk, W.E.; McDade, E.; Martins, R.N.; Masters, C.L.; Mayeux, R.; Ringman, J.M.; Rossor, M.N.; Schofield, P.R.; Sperling, R.A.; Salloway, S.; Morris, J.C. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N. Engl. J. Med., 2012, 367(9), 795-804.
[http://dx.doi.org/10.1056/NEJMoa1202753] [PMID: 22784036]
[27]
Du, X.; Wang, X.; Geng, M. Alzheimer’s disease hypothesis and related therapies. Transl. Neurodegener., 2018, 7(1), 2.
[http://dx.doi.org/10.1186/s40035-018-0107-y] [PMID: 29423193]
[28]
Vaz, M.; Silvestre, S. Alzheimer’s disease: Recent treatment strategies. Eur. J. Pharmacol., 2020, 887(887), 173554.
[http://dx.doi.org/10.1016/j.ejphar.2020.173554] [PMID: 32941929]
[29]
Hardy, J.A.; Higgins, G.A. Alzheimer’s disease: The amyloid cascade hypothesis. Science, 1992, 256(5054), 184-185.
[http://dx.doi.org/10.1126/science.1566067] [PMID: 1566067]
[30]
Hardy, J.; Selkoe, D.J. The amyloid hypothesis of Alzheimer’s disease: Progress and problems on the road to therapeutics. Science, 2002, 297(5580), 353-356.
[http://dx.doi.org/10.1126/science.1072994] [PMID: 12130773]
[31]
Musiek, E.S.; Holtzman, D.M. Three dimensions of the amyloid hypothesis: Time, space and ‘wingmen’. Nat. Neurosci., 2015, 18(6), 800-806.
[http://dx.doi.org/10.1038/nn.4018] [PMID: 26007213]
[32]
Barage, S.H.; Sonawane, K.D. Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer’s disease. Neuropeptides, 2015, 52, 1-18.
[http://dx.doi.org/10.1016/j.npep.2015.06.008] [PMID: 26149638]
[33]
Karran, E.; De Strooper, B. The amyloid cascade hypothesis: Are we poised for success or failure? J. Neurochem., 2016, 139(Suppl. 2), 237-252.
[http://dx.doi.org/10.1111/jnc.13632] [PMID: 27255958]
[34]
Long, J.M.; Holtzman, D.M. Alzheimer disease: An update on pathobiology and treatment strategies. Cell, 2019, 179(2), 312-339.
[http://dx.doi.org/10.1016/j.cell.2019.09.001] [PMID: 31564456]
[35]
Lambert, J.C.; Ibrahim-Verbaas, C.A.; Harold, D.; Naj, A.C.; Sims, R.; Bellenguez, C.; Jun, G.; DeStefano, A.L.; Bis, J.C.; Beecham, G.W.; Grenier-Boley, B.; Russo, G.; Thornton-Wells, T.A.; Jones, N.; Smith, A.V.; Chouraki, V.; Thomas, C.; Ikram, M.A.; Zelenika, D.; Vardarajan, B.N.; Kamatani, Y.; Lin, C-F.; Gerrish, A.; Schmidt, H.; Kunkle, B.; Dunstan, M.L.; Ruiz, A.; Bihoreau, M-T.; Choi, S-H.; Reitz, C.; Pasquier, F.; Hollingworth, P.; Ramirez, A.; Hanon, O.; Fitzpatrick, A.L.; Buxbaum, J.D.; Campion, D.; Crane, P.K.; Baldwin, C.; Becker, T.; Gudnason, V.; Cruchaga, C.; Craig, D.; Amin, N.; Berr, C.; Lopez, O.L.; De Jager, P.L.; Deramecourt, V.; Johnston, J.A.; Evans, D.; Lovestone, S.; Letenneur, L.; Morón, F.J.; Rubinsztein, D.C.; Eiriksdottir, G.; Sleegers, K.; Goate, A.M.; Fiévet, N.; Huentelman, M.J.; Gill, M.; Brown, K.; Kamboh, M.I.; Keller, L.; Barberger-Gateau, P.; McGuinness, B.; Larson, E.B.; Green, R.; Myers, A.J.; Dufouil, C.; Todd, S.; Wallon, D.; Love, S.; Rogaeva, E.; Gallacher, J.; St George-Hyslop, P.; Clarimon, J.; Lleo, A.; Bayer, A.; Tsuang, D.W.; Yu, L.; Tsolaki, M.; Bossù, P.; Spalletta, G.; Proitsi, P.; Collinge, J.; Sorbi, S.; Sanchez-Garcia, F.; Fox, N.C.; Hardy, J.; Naranjo, M.C.D.; Bosco, P.; Clarke, R.; Brayne, C.; Galimberti, D.; Mancuso, M.; Matthews, F.; Moebus, S.; Mecocci, P.; Del Zompo, M.; Maier, W.; Hampel, H.; Pilotto, A.; Bullido, M.; Panza, F.; Caffarra, P.; Nacmias, B.; Gilbert, J.R.; Mayhaus, M.; Lannfelt, L.; Hakonarson, H.; Pichler, S.; Carrasquillo, M.M.; Ingelsson, M.; Beekly, D.; Alvarez, V.; Zou, F.; Valladares, O.; Younkin, S.G.; Coto, E.; Hamilton-Nelson, K.L.; Gu, W.; Razquin, C.; Pastor, P.; Mateo, I.; Owen, M.J.; Faber, K.M.; Jonsson, P.V.; Combarros, O.; O’Donovan, M.C.; Cantwell, L.B.; Soininen, H.; Blacker, D.; Mead, S.; Mosley, T.H., Jr; Bennett, D.A.; Harris, T.B.; Fratiglioni, L.; Holmes, C.; de Bruijn, R.F.A.G.; Passmore, P.; Montine, T.J.; Bettens, K.; Rotter, J.I.; Brice, A.; Morgan, K.; Foroud, T.M.; Kukull, W.A.; Hannequin, D.; Powell, J.F.; Nalls, M.A.; Ritchie, K.; Lunetta, K.L.; Kauwe, J.S.K.; Boerwinkle, E.; Riemenschneider, M.; Boada, M.; Hiltunen, M.; Martin, E.R.; Schmidt, R.; Rujescu, D.; Wang, L.S.; Dartigues, J.F.; Mayeux, R.; Tzourio, C.; Hofman, A.; Nöthen, M.M.; Graff, C.; Psaty, B.M.; Jones, L.; Haines, J.L.; Holmans, P.A.; Lathrop, M.; Pericak-Vance, M.A.; Launer, L.J.; Farrer, L.A.; van Duijn, C.M.; Van Broeckhoven, C.; Moskvina, V.; Seshadri, S.; Williams, J.; Schellenberg, G.D.; Amouyel, P. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat. Genet., 2013, 45(12), 1452-1458.
[http://dx.doi.org/10.1038/ng.2802] [PMID: 24162737]
[36]
Mesulam, M.M. Neuroplasticity failure in Alzheimer’s disease: Bridging the gap between plaques and tangles. Neuron, 1999, 24(3), 521-529.
[http://dx.doi.org/10.1016/S0896-6273(00)81109-5] [PMID: 10595506]
[37]
Nelson, P.T.; Alafuzoff, I.; Bigio, E.H.; Bouras, C.; Braak, H.; Cairns, N.J.; Castellani, R.J.; Crain, B.J.; Davies, P.; Tredici, K.D.; Duyckaerts, C.; Frosch, M.P.; Haroutunian, V.; Hof, P.R.; Hulette, C.M.; Hyman, B.T.; Iwatsubo, T.; Jellinger, K.A.; Jicha, G.A.; Kövari, E.; Kukull, W.A.; Leverenz, J.B.; Love, S.; Mackenzie, I.R.; Mann, D.M.; Masliah, E.; McKee, A.C.; Montine, T.J.; Morris, J.C.; Schneider, J.A.; Sonnen, J.A.; Thal, D.R.; Trojanowski, J.Q.; Troncoso, J.C.; Wisniewski, T.; Woltjer, R.L.; Beach, T.G. Correlation of Alzheimer disease neuropathologic changes with cognitive status: A review of the literature. J. Neuropathol. Exp. Neurol., 2012, 71(5), 362-381.
[http://dx.doi.org/10.1097/NEN.0b013e31825018f7] [PMID: 22487856]
[38]
Van Der Kant, R.; Goldstein, L.S.B.; Ossenkoppele, R. Amyloid-β-independent regulators of tau pathology in Alzheimer disease. Nat. Rev. Neurosci., 2020, 21(1), 21-35.
[http://dx.doi.org/10.1038/s41583-019-0240-3] [PMID: 31780819]
[39]
Braak, H.; Braak, E. Neuropathological stageing of Alzheimer related changes. Acta Neuropathol., 1991, 82(4), 239-259.
[http://dx.doi.org/10.1007/BF00308809] [PMID: 1759558]
[40]
Sato, C.; Barthélemy, N.R.; Mawuenyega, K.G.; Patterson, B.W.; Gordon, B.A.; Jockel-Balsarotti, J.; Sullivan, M.; Crisp, M.J.; Kasten, T.; Kirmess, K.M.; Kanaan, N.M.; Yarasheski, K.E.; Baker, N.A.; Benzinger, T.L.S.; Miller, T.M.; Karch, C.M.; Bateman, R.J. Tau kinetics in neurons and the human central nervous system. Neuron, 2018, 97(6), 1284-1298.e7.
[http://dx.doi.org/10.1016/j.neuron.2018.02.015] [PMID: 29566794]
[41]
Lippens, G.; Gigant, B. Elucidating Tau function and dysfunction in the era of cryo-EM. J. Biol. Chem., 2019, 294(24), 9316-9325.
[http://dx.doi.org/10.1074/jbc.REV119.008031] [PMID: 31088912]
[42]
Gao, Y.; Tan, L.; Yu, J.T.; Tan, L. Tau in Alzheimer’s disease: Mechanisms and therapeutic strategies. Curr. Alzheimer Res., 2018, 15(3), 283-300.
[http://dx.doi.org/10.2174/1567205014666170417111859] [PMID: 28413986]
[43]
Onyango, I.G.; Jauregui, G.V.; Čarná, M.; Bennett, J.P., Jr; Stokin, G.B. Neuroinflammation in Alzheimer’s disease. Biomedicines, 2021, 9(5), 524.
[http://dx.doi.org/10.3390/biomedicines9050524] [PMID: 34067173]
[44]
De Sousa, R.A.L. Reactive gliosis in Alzheimer’s disease: A crucial role for cognitive impairment and memory loss. Metab. Brain Dis., 2022, 37(4), 851-857.
[http://dx.doi.org/10.1007/s11011-022-00953-2] [PMID: 35286534]
[45]
Piccioni, G.; Mango, D.; Saidi, A.; Corbo, M.; Nisticò, R. Targeting microglia synapse interactions in Alzheimer’s disease. Int. J. Mol. Sci., 2021, 22(5), 2342.
[http://dx.doi.org/10.3390/ijms22052342] [PMID: 33652870]
[46]
Avila, J.; Gómez, R.A.; Bolós, M. AD genetic risk factors and tau spreading. Front. Aging Neurosci., 2015, 7, 99.
[http://dx.doi.org/10.3389/fnagi.2015.00099] [PMID: 26052285]
[47]
Penke, B.; Bogár, F.; Crul, T.; Sántha, M.; Tóth, M.; Vígh, L. Heat shock proteins and autophagy pathways in neuroprotection: From molecular bases to pharmacological interventions. Int. J. Mol. Sci., 2018, 19(1), 325.
[http://dx.doi.org/10.3390/ijms19010325] [PMID: 29361800]
[48]
Caspersen, C.; Wang, N.; Yao, J.; Sosunov, A.; Chen, X.; Lustbader, J.W.; Xu, H.W.; Stern, D.; McKhann, G.; Du Yan, S. Mitochondrial Aβ: A potential focal point for neuronal metabolic dysfunction in Alzheimer’s disease. FASEB J., 2005, 19(14), 2040-2041.
[http://dx.doi.org/10.1096/fj.05-3735fje] [PMID: 16210396]
[49]
McManus, M.J.; Murphy, M.P.; Franklin, J.L. The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease. J. Neurosci., 2011, 31(44), 15703-15715.
[http://dx.doi.org/10.1523/JNEUROSCI.0552-11.2011] [PMID: 22049413]
[50]
Chen, Z.R.; Huang, J.B.; Yang, S.L.; Hong, F.F. Role of cholinergic signaling in Alzheimer’s disease. Molecules, 2022, 27(6), 1816.
[http://dx.doi.org/10.3390/molecules27061816] [PMID: 35335180]
[51]
Agatonovic, K.S.; Kettle, C.; Morton, D.W. A molecular approach in drug development for Alzheimer’s disease. Biomed. Pharmacother., 2018, 106, 553-565.
[http://dx.doi.org/10.1016/j.biopha.2018.06.147] [PMID: 29990843]
[52]
Calhoun, A.; King, C.; Khoury, R.; Grossberg, G.T. An evaluation of memantine ER + donepezil for the treatment of Alzheimer’s disease. Expert Opin. Pharmacother., 2018, 19(15), 1711-1717.
[http://dx.doi.org/10.1080/14656566.2018.1519022] [PMID: 30244611]
[53]
Shigeta, M.; Homma, A. Donepezil for Alzheimer’s disease: Pharmacodynamic, pharmacokinetic, and clinical profiles. CNS Drug Rev., 2001, 7(4), 353-368.
[http://dx.doi.org/10.1111/j.1527-3458.2001.tb00204.x] [PMID: 11830754]
[54]
Terry, A.V., Jr; Buccafusco, J.J. The cholinergic hypothesis of age and Alzheimer’s disease-related cognitive deficits: Recent challenges and their implications for novel drug development. J. Pharmacol. Exp. Ther., 2003, 306(3), 821-827.
[http://dx.doi.org/10.1124/jpet.102.041616] [PMID: 12805474]
[55]
Namenda, XR (memantine hydrochloride) drug approval package. 2010. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022525s000_namenda_xr _toc.cfm
[56]
Parsons, C.G.; 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.
[http://dx.doi.org/10.1007/s12640-013-9398-z] [PMID: 23657927]
[57]
Patel, L.; Grossberg, G.T. Combination therapy for Alzheimer’s disease. Drugs Aging, 2011, 28(7), 539-546.
[http://dx.doi.org/10.2165/11591860-000000000-00000] [PMID: 21721598]
[58]
Kabir, M.T.; Uddin, M.S.; Mamun, A.A.; Jeandet, P.; Aleya, L.; Mansouri, R.A.; Ashraf, G.M.; Mathew, B.; Bin-Jumah, M.N.; Abdel, D.M.M. Combination drug therapy for the management of Alzheimer’s disease. Int. J. Mol. Sci., 2020, 21(9), 3272.
[http://dx.doi.org/10.3390/ijms21093272] [PMID: 32380758]
[59]
Posadas, I.; López, H.B.; Ceña, V. Nicotinic receptors in neurodegeneration. Curr. Neuropharmacol., 2013, 11(3), 298-314.
[http://dx.doi.org/10.2174/1570159X11311030005] [PMID: 24179465]
[60]
Takada, T.Y.; Kume, T.; Sugimoto, M.; Katsuki, H.; Sugimoto, H.; Akaike, A. Acetylcholinesterase inhibitors used in treatment of Alzheimer’s disease prevent glutamate neurotoxicity via nicotinic acetylcholine receptors and phosphatidylinositol 3-kinase cascade. Neuropharmacology, 2006, 51(3), 474-486.
[http://dx.doi.org/10.1016/j.neuropharm.2006.04.007] [PMID: 16762377]
[61]
Simoni, E.; Daniele, S.; Bottegoni, G.; Pizzirani, D.; Trincavelli, M.L.; Goldoni, L.; Tarozzo, G.; Reggiani, A.; Martini, C.; Piomelli, D.; Melchiorre, C.; Rosini, M.; Cavalli, A. Combining galantamine and memantine in multitargeted, new chemical entities potentially useful in Alzheimer’s disease. J. Med. Chem., 2012, 55(22), 9708-9721.
[http://dx.doi.org/10.1021/jm3009458] [PMID: 23033965]
[62]
Lopes, J.P.; Tarozzo, G.; Reggiani, A.; Piomelli, D.; Cavalli, A. Galantamine potentiates the neuroprotective effect of memantine against NMDA-induced excitotoxicity. Brain Behav., 2013, 3(2), 67-74.
[http://dx.doi.org/10.1002/brb3.118] [PMID: 23532860]
[63]
Rosini, M.; Simoni, E.; Bartolini, M.; Cavalli, A.; Ceccarini, L.; Pascu, N.; McClymont, D.W.; Tarozzi, A.; Bolognesi, M.L.; Minarini, A.; Tumiatti, V.; Andrisano, V.; Mellor, I.R.; Melchiorre, C. Inhibition of acetylcholinesterase, beta-amyloid aggregation, and NMDA receptors in Alzheimer’s disease: A promising direction for the multi-target-directed ligands gold rush. J. Med. Chem., 2008, 51(15), 4381-4384.
[http://dx.doi.org/10.1021/jm800577j] [PMID: 18605718]
[64]
Lipton, S.A. Paradigm shift in neuroprotection by NMDA receptor blockade: Memantine and beyond. Nat. Rev. Drug Discov., 2006, 5(2), 160-170.
[http://dx.doi.org/10.1038/nrd1958] [PMID: 16424917]
[65]
Lipton, S.A.; Choi, Y.B.; Pan, Z.H.; Lei, S.Z.; Chen, H.S.V.; Sucher, N.J.; Loscalzo, J.; Singel, D.J.; Stamler, J.S. A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature, 1993, 364(6438), 626-632.
[http://dx.doi.org/10.1038/364626a0] [PMID: 8394509]
[66]
Zheng, H.; Fridkin, M.; Youdim, M. From single target to multitarget/network therapeutics in Alzheimer’s therapy. Pharmaceuticals, 2014, 7(2), 113-135.
[http://dx.doi.org/10.3390/ph7020113] [PMID: 24463342]
[67]
Serrano, P.A.; William, C.M.; Ferrer, I.; Uro, C.E.; Delisle, M.B.; Maurage, C.A.; Hock, C.; Nitsch, R.M.; Masliah, E.; Growdon, J.H.; Frosch, M.P.; Hyman, B.T. Beneficial effect of human anti-amyloid-β active immunization on neurite morphology and Tau pathology. Brain, 2010, 133(5), 1312-1327.
[http://dx.doi.org/10.1093/brain/awq056] [PMID: 20360050]
[68]
Dodel, R.; Rominger, A.; Bartenstein, P.; Barkhof, F.; Blennow, K.; Förster, S.; Winter, Y.; Bach, J.P.; Popp, J.; Alferink, J.; Wiltfang, J.; Buerger, K.; Otto, M.; Antuono, P.; Jacoby, M.; Richter, R.; Stevens, J.; Melamed, I.; Goldstein, J.; Haag, S.; Wietek, S.; Farlow, M.; Jessen, F. Intravenous immunoglobulin for treatment of mild-to-moderate Alzheimer’s disease: A phase 2, randomised, double-blind, placebo-controlled, dose-finding trial. Lancet Neurol., 2013, 12(3), 233-243.
[http://dx.doi.org/10.1016/S1474-4422(13)70014-0] [PMID: 23375965]
[69]
Prati, F.; Bergamini, C.; Fato, R.; Soukup, O.; Korabecny, J.; Andrisano, V.; Bartolini, M.; Bolognesi, M.L. Novel 8-hydroxyquinoline derivatives as multitarget compounds for the treatment of Alzheimer’s disease. ChemMedChem, 2016, 11(12), 1284-1295.
[http://dx.doi.org/10.1002/cmdc.201600014] [PMID: 26880501]
[70]
Suh, S.W.; Jensen, K.B.; Jensen, M.S.; Silva, D.S.; Kesslak, P.J.; Danscher, G.; Frederickson, C.J. Histochemically reactive zinc in amyloid plaques, angiopathy, and degenerating neurons of Alzheimer’s diseased brains. Brain Res., 2000, 852(2), 274-278.
[http://dx.doi.org/10.1016/S0006-8993(99)02096-X] [PMID: 10678753]
[71]
Curtain, C.C.; Ali, F.; Volitakis, I.; Cherny, R.A.; Norton, R.S.; Beyreuther, K.; Barrow, C.J.; Masters, C.L.; Bush, A.I.; Barnham, K.J. Alzheimer’s disease amyloid-beta binds copper and zinc to generate an allosterically ordered membrane-penetrating structure containing superoxide dismutase-like subunits. J. Biol. Chem., 2001, 276(23), 20466-20473.
[http://dx.doi.org/10.1074/jbc.M100175200] [PMID: 11274207]
[72]
Fernández, B.M.I.; Pérez, C.; González, M.G.C.; Conde, S.; López, M.G.; Villarroya, M.; García, A.G.; Rodríguez, F.M.I. Novel tacrine-8-hydroxyquinoline hybrids as multifunctional agents for the treatment of Alzheimer’s disease, with neuroprotective, cholinergic, antioxidant, and copper-complexing properties. J. Med. Chem., 2010, 53(13), 4927-4937.
[http://dx.doi.org/10.1021/jm100329q] [PMID: 20545360]
[73]
Peña, A.E.; Prati, F.; Massenzio, F.; Virgili, M.; Contestabile, A.; Bolognesi, M.L.; Monti, B. Changing paradigm to target microglia in neurodegenerative diseases: From anti-inflammatory strategy to active immunomodulation. Expert Opin. Ther. Targets, 2016, 20(5), 627-640.
[http://dx.doi.org/10.1517/14728222.2016.1121237] [PMID: 26568363]
[74]
Weinstock, M.; Bejar, C.; Wang, R-H.; Poltyrev, T.; Gross, A.; Finberg, J.P.M.; Youdim, M.B.H. TV3326, a novel neuroprotective drug with cholinesterase and monoamine oxidase inhibitory activities for the treatment of Alzheimer’s disease. In: Advances in Research on Neurodegeneration; Mizuno, Y.; Youdim, M.B.H.; Calne, D.B.; Horowski, R.; Poewe, W.; Riederer, P.; Youdim, M.B.H., Eds.; Springer: Vienna, Austria, 2000; 10, pp. 157-169.
[http://dx.doi.org/10.1007/978-3-7091-6301-6_10]
[75]
Bar, A.O.; Weinreb, O.; Amit, T.; Youdim, M.B.H. The novel cholinesterase-monoamine oxidase inhibitor and antioxidant, ladostigil, confers neuroprotection in neuroblastoma cells and aged rats. J. Mol. Neurosci., 2009, 37(2), 135-145.
[http://dx.doi.org/10.1007/s12031-008-9139-6] [PMID: 18751929]
[76]
Bar, A.O.; Yogev, F.M.; Amit, T.; Sagi, Y.; Youdim, M.B.H. Regulation of protein kinase C by the anti-Parkinson drug, MAO-B inhibitor, rasagiline and its derivatives, in vivo. J. Neurochem., 2004, 89(5), 1119-1125.
[http://dx.doi.org/10.1111/j.1471-4159.2004.02425.x] [PMID: 15147504]
[77]
Weinreb, O.; Amit, T.; Bar-Am, O.; Youdim, M.B.H. Rasagiline: A novel anti-Parkinsonian monoamine oxidase-B inhibitor with neuroprotective activity. Prog. Neurobiol., 2010, 92(3), 330-344.
[http://dx.doi.org/10.1016/j.pneurobio.2010.06.008] [PMID: 20600573]
[78]
Faux, N.G.; Ritchie, C.W.; Gunn, A.; Rembach, A.; Tsatsanis, A.; Bedo, J.; Harrison, J.; Lannfelt, L.; Blennow, K.; Zetterberg, H.; Ingelsson, M.; Masters, C.L.; Tanzi, R.E.; Cummings, J.L.; Herd, C.M.; Bush, A.I. PBT2 rapidly improves cognition in Alzheimer’s Disease: Additional phase II analyses. J. Alzheimers Dis., 2010, 20(2), 509-516.
[http://dx.doi.org/10.3233/JAD-2010-1390] [PMID: 20164561]
[79]
Savelieff, M.G.; DeToma, A.S.; Derrick, J.S.; Lim, M.H. The ongoing search for small molecules to study metal-associated amyloid-β species in Alzheimer’s disease. Acc. Chem. Res., 2014, 47(8), 2475-2482.
[http://dx.doi.org/10.1021/ar500152x] [PMID: 25080056]
[80]
Gal, S.; Zheng, H.; Fridkin, M.; Youdim, M.B.H. Novel multifunctional neuroprotective iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases. In vivo selective brain monoamine oxidase inhibition and prevention of MPTP-induced striatal dopamine depletion. J. Neurochem., 2005, 95(1), 79-88.
[http://dx.doi.org/10.1111/j.1471-4159.2005.03341.x] [PMID: 16181414]
[81]
Zheng, H.; Gal, S.; Weiner, L.M.; Bar, A.O.; Warshawsky, A.; Fridkin, M.; Youdim, M.B.H. Novel multifunctional neuroprotective iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases: In vitro studies on antioxidant activity, prevention of lipid peroxide formation and monoamine oxidase inhibition. J. Neurochem., 2005, 95(1), 68-78.
[http://dx.doi.org/10.1111/j.1471-4159.2005.03340.x] [PMID: 16181413]
[82]
Kupershmidt, L.; Amit, T.; Bar-Am, O.; Weinreb, O.; Youdim, M.B.H. Multi-target, neuroprotective and neurorestorative M30 improves cognitive impairment and reduces Alzheimer’s-like neuropathology and age-related alterations in mice. Mol. Neurobiol., 2012, 46(1), 217-220.
[http://dx.doi.org/10.1007/s12035-012-8304-7] [PMID: 22847630]
[83]
Kupershmidt, L.; Amit, T.; Bar, A.O.; Youdim, M.B.H.; Weinreb, O. Neuroprotection by the multitarget iron chelator M30 on age-related alterations in mice. Mech. Ageing Dev., 2012, 133(5), 267-274.
[http://dx.doi.org/10.1016/j.mad.2012.03.001] [PMID: 22426424]
[84]
Gannon, M.; Wang, Q. Complex noradrenergic dysfunction in Alzheimer’s disease: Low norepinephrine input is not always to blame. Brain Res., 2019, 1702, 12-16.
[http://dx.doi.org/10.1016/j.brainres.2018.01.001] [PMID: 29307592]
[85]
Gannon, M.; Che, P.; Chen, Y.; Jiao, K.; Roberson, E.D.; Wang, Q. Noradrenergic dysfunction in Alzheimer’s disease. Front. Neurosci., 2015, 9, 220.
[http://dx.doi.org/10.3389/fnins.2015.00220] [PMID: 26136654]
[86]
Mohs, R.C.; Shiovitz, T.M.; Tariot, P.N.; Porsteinsson, A.P.; Baker, K.D.; Feldman, P.D. Atomoxetine augmentation of cholinesterase inhibitor therapy in patients with Alzheimer disease: 6-month, randomized, double-blind, placebo-controlled, parallel-trial study. Am. J. Geriatr. Psychiatry, 2009, 17(9), 752-759.
[http://dx.doi.org/10.1097/JGP.0b013e3181aad585] [PMID: 19700948]
[87]
Congdon, E.E.; Sigurdsson, E.M. Tau-targeting therapies for Alzheimer disease. Nat. Rev. Neurol., 2018, 14(7), 399-415.
[http://dx.doi.org/10.1038/s41582-018-0013-z] [PMID: 29895964]
[88]
Fleisher, A.S.; Truran, D.; Mai, J.T.; Langbaum, J.B.S.; Aisen, P.S.; Cummings, J.L.; Jack, C.R., Jr; Weiner, M.W.; Thomas, R.G.; Schneider, L.S.; Tariot, P.N. Chronic divalproex sodium use and brain atrophy in Alzheimer disease. Neurology, 2011, 77(13), 1263-1271.
[http://dx.doi.org/10.1212/WNL.0b013e318230a16c] [PMID: 21917762]
[89]
Tariot, P.N.; Schneider, L.S.; Cummings, J.; Thomas, R.G.; Raman, R.; Jakimovich, L.J.; Loy, R.; Bartocci, B.; Fleisher, A.; Ismail, M.S.; Porsteinsson, A.; Weiner, M.; Jack, C.R., Jr; Thal, L.; Aisen, P.S. Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease. Arch. Gen. Psychiatry, 2011, 68(8), 853-861.
[http://dx.doi.org/10.1001/archgenpsychiatry.2011.72] [PMID: 21810649]
[90]
Álvarez, A.; Cacabelos, R.; Sanpedro, C.; García-Fantini, M.; Aleixandre, M. Serum TNF-alpha levels are increased and correlate negatively with free IGF-I in Alzheimer disease. Neurobiol. Aging, 2007, 28(4), 533-536.
[http://dx.doi.org/10.1016/j.neurobiolaging.2006.02.012] [PMID: 16569464]
[91]
Mufson, E.; Counts, S.; Fahnestock, M.; Ginsberg, S. Cholinotrophic molecular substrates of mild cognitive impairment in the elderly. Curr. Alzheimer Res., 2007, 4(4), 340-350.
[http://dx.doi.org/10.2174/156720507781788855] [PMID: 17908035]
[92]
Schindowski, K.; Belarbi, K.; Buée, L. Neurotrophic factors in Alzheimer’s disease: Role of axonal transport. In: Proceedings of the Genes, Brain and Behavior; Blackwell Publishing Ltd, Newark, NJ, USA, 2008; 7, pp. 43-56.
[http://dx.doi.org/10.1111/j.1601-183X.2007.00378.x]
[93]
Alvarez, X.A.; Cacabelos, R.; Sampedro, C.; Couceiro, V.; Aleixandre, M.; Vargas, M.; Linares, C.; Granizo, E.; García, F.M.; Baurecht, W.; Doppler, E.; Moessler, H. Combination treatment in Alzheimer’s disease: Results of a randomized, controlled trial with cerebrolysin and donepezil. Curr. Alzheimer Res., 2011, 8(5), 583-591.
[http://dx.doi.org/10.2174/156720511796391863] [PMID: 21679156]
[94]
Martel, J.C.; Assié, M.B.; Bardin, L.; Depoortère, R.; Cussac, D.; Newman, T.A. 5-HT 1A receptors are involved in the effects of xaliproden on G-protein activation, neurotransmitter release and nociception. Br. J. Pharmacol., 2009, 158(1), 232-242.
[http://dx.doi.org/10.1111/j.1476-5381.2009.00249.x] [PMID: 19508400]
[95]
Study of xaliproden (SR57746A) in patients with mild-tomoderate Dementia of the Alzheimer's type. NCT00104013, Available from: https://clinicaltrials.gov/ct2/show/NCT00104013 (Accessed on: 16 Feb 2022).
[96]
Sevigny, J.J.; Ryan, J.M.; van Dyck, C.H.; Peng, Y.; Lines, C.R.; Nessly, M.L. Growth hormone secretagogue MK-677: No clinical effect on AD progression in a randomized trial. Neurology, 2008, 71(21), 1702-1708.
[http://dx.doi.org/10.1212/01.wnl.0000335163.88054.e7] [PMID: 19015485]
[97]
Yesmin, B.; Oscar, H.C.; Begum, M.M.; Begum, Y.; Herrera, C.O.; Islam, M.M.; Abdel, D.M.M. Inspection of phytochemical content and in vitro antioxidant profile of Gnaphalium luteoalbum L.: An unexplored phytomedicine. J. Pharm. Nutr. Sci., 2017, 7(3), 136-146.
[http://dx.doi.org/10.6000/1927-5951.2017.07.03.10]
[98]
Hossain, M.S.; Uddin, M.S.; Kabir, M.T.; Begum, M.M.; Koushal, P.; Herrera, C.O.; Akter, R.; Asaduzzaman, M.; Abdel, D.M.M. In vitro screening for phytochemicals and antioxidant activities of Syngonium podophyllum L.: An incredible therapeutic plant. Biomed. Pharmacol. J., 2017, 10(3), 1267-1277.
[http://dx.doi.org/10.13005/bpj/1229]
[99]
Uddin, M.; Hossain, M.; Al Mamun, A.; Tewari, D.; Asaduzzaman, M.; Islam, M.; Abdel, D.M. Phytochemical analysis and antioxidant profile of methanolic extract of seed, pulp and peel of Baccaurea ramiflora Lour. Asian Pac. J. Trop. Med., 2018, 11(7), 443.
[http://dx.doi.org/10.4103/1995-7645.237189]
[100]
Imon, R.; Devesh, T.; Kabir, M.T.; Rahman, I.; Tewari, D.; Jamiruddin, M.R.; Al Mamun, A. Phytochemical screening and antioxidant profile of Syngonium podophyllum Schott stems: A fecund phytopharmakon. J. Pharm. Nutr. Sci., 2018, 8(3), 120-128.
[http://dx.doi.org/10.6000/1927-5951.2018.08.03.6]
[101]
Uddin, M.S.; Kabir, M.T. Oxidative stress in Alzheimer’s disease: Molecular hallmarks of underlying vulnerability. In: Biological, Diagnostic and Therapeutic Advances in Alzheimer’s Disease; Ashraf, G.M.; Alexiou, A., Eds.; Springer: Singapore, 2019; pp. 91-115.
[102]
Uddin, M.S.; Upaganlawar, A.B. Oxidative Stress and Antioxidant Defense: Biomedical Value in Health and Diseases; Nova Science Publishers: New York, NY, USA, 2019.
[103]
Uddin, M.; Rahman, A.; Haque, A.; Mian, M.; Sufian, M.; Rahman, M.; Ali, Y.; Rafe, M.; Abdel, D.M.; Uddin, M.; Asaduzzaman, M. In vitro screening for antioxidant and anticholinesterase effects of Uvaria littoralis Blume.: A nootropic phytotherapeutic remedy. J. Intellect. Disabil. –. Diagn. Treat., 2017, 5(2), 50-60.
[http://dx.doi.org/10.6000/2292-2598.2017.05.02.3]
[104]
Sano, M.; Ernesto, C.; Thomas, R.G.; Klauber, M.R.; Schafer, K.; Grundman, M.; Woodbury, P.; Growdon, J.; Cotman, C.W.; Pfeiffer, E.; Schneider, L.S.; Thal, L.J. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s disease cooperative study. N. Engl. J. Med., 1997, 336(17), 1216-1222.
[http://dx.doi.org/10.1056/NEJM199704243361704] [PMID: 9110909]
[105]
Klatte, E.T.; Scharre, D.W.; Nagaraja, H.N.; Davis, R.A.; Beversdorf, D.Q. Combination therapy of donepezil and vitamin E in Alzheimer disease. Alzheimer Dis. Assoc. Disord., 2003, 17(2), 113-116.
[http://dx.doi.org/10.1097/00002093-200304000-00010] [PMID: 12794389]
[106]
Aisen, P.S.; Schneider, L.S.; Sano, M.; Diaz, A.R.; Van Dyck, C.H.; Weiner, M.F.; Bottiglieri, T.; Jin, S.; Stokes, K.T.; Thomas, R.G.; Thal, L.J. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: A randomized controlled trial. JAMA, 2008, 300(15), 1774-1783.
[http://dx.doi.org/10.1001/jama.300.15.1774] [PMID: 18854539]
[107]
Quinn, J.F.; Raman, R.; Thomas, R.G.; Yurko, M.K.; Nelson, E.B.; Van Dyck, C.; Galvin, J.E.; Emond, J.; Jack, C.R., Jr; Weiner, M.; Shinto, L.; Aisen, P.S. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: A randomized trial. JAMA, 2010, 304(17), 1903-1911.
[http://dx.doi.org/10.1001/jama.2010.1510] [PMID: 21045096]
[108]
Freund, L.Y.; Eriksdotter, J.M.; Cederholm, T.; Basun, H.; Faxén, I.G.; Garlind, A.; Vedin, I.; Vessby, B.; Wahlund, L.O.; Palmblad, J. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: A randomized double-blind trial. Arch. Neurol., 2006, 63(10), 1402-1408.
[http://dx.doi.org/10.1001/archneur.63.10.1402] [PMID: 17030655]
[109]
Hossain, M.; Uddin, M.; Kabir, M.; Akhter, S.; Goswami, S.; Mamun, A.; Herrera-Calderon, O.; Abdel, D.M.; Abdel, D.M.M. In vivo screening for analgesic and anti-inflammatory activities of Syngonium podophyllum L.: A remarkable herbal medicine. Annu. Res. Rev. Biol., 2017, 16(3), 1-12.
[http://dx.doi.org/10.9734/ARRB/2017/35692]
[110]
Begum, M.M.; Islam, A.; Begum, R.; Uddin, M.S.; Rahman, M.S.; Alam, S.; Akter, W.; Das, M.; Rahman, M.S.; Imon, A.H.M.R. Ethnopharmacological inspections of organic extract of Oroxylum indicum in rat models: A promising natural gift. Evidence-based complement. Altern. Med., 2019, 2019, 1562038.
[http://dx.doi.org/10.1155/2019/1562038] [PMID: 31073315]
[111]
Moore, A.H.; Bigbee, M.J.; Boynton, G.E.; Wakeham, C.M.; Rosenheim, H.M.; Staral, C.J.; Morrissey, J.L.; Hund, A.K. Non-steroidal anti-inflammatory drugs in Alzheimer’s disease and Parkinson’s disease: Reconsidering the role of neuroinflammation. Pharmaceuticals, 2010, 3(6), 1812-1841.
[http://dx.doi.org/10.3390/ph3061812] [PMID: 27713331]
[112]
Pasqualetti, P.; Bonomini, C.; Dal Forno, G.; Paulon, L.; Sinforiani, E.; Marra, C.; Zanetti, O.; Maria Rossini, P. A randomized controlled study on effects of ibuprofen on cognitive progression of Alzheimer’s disease. Aging Clin. Exp. Res., 2009, 21(2), 102-110.
[http://dx.doi.org/10.1007/BF03325217] [PMID: 19448381]
[113]
Soininen, H.; West, C.; Robbins, J.; Niculescu, L. Long-term efficacy and safety of celecoxib in Alzheimer’s disease. Dement. Geriatr. Cogn. Disord., 2007, 23(1), 8-21.
[http://dx.doi.org/10.1159/000096588] [PMID: 17068392]
[114]
Aisen, P.S.; Schafer, K.A.; Grundman, M.; Pfeiffer, E.; Sano, M.; Davis, K.L.; Farlow, M.R.; Jin, S.; Thomas, R.G.; Thal, L.J. Effects of rofecoxib or naproxen vs. placebo on Alzheimer disease progression: A randomized controlled trial. JAMA, 2003, 289(21), 2819-2826.
[http://dx.doi.org/10.1001/jama.289.21.2819] [PMID: 12783912]
[115]
Zhong, K.L.; Chen, F.; Hong, H.; Ke, X.; Lv, Y.G.; Tang, S.S.; Zhu, Y.B. New views and possibilities of antidiabetic drugs in treating and/or preventing mild cognitive impairment and Alzheimer’s disease. Metab. Brain Dis., 2018, 33(4), 1009-1018.
[http://dx.doi.org/10.1007/s11011-018-0227-1] [PMID: 29626315]
[116]
Plastino, M.; Fava, A.; Pirritano, D.; Cotronei, P.; Sacco, N.; Sperlì, T.; Spanò, A.; Gallo, D.; Mungari, P.; Consoli, D.; Bosco, D. Effects of insulinic therapy on cognitive impairment in patients with Alzheimer disease and diabetes mellitus type-2. J. Neurol. Sci., 2010, 288(1-2), 112-116.
[http://dx.doi.org/10.1016/j.jns.2009.09.022] [PMID: 19836029]
[117]
Sharma, K. Cholinesterase inhibitors as Alzheimer’s therapeutics. Mol. Med. Rep., 2019, 20(2), 1479-1487.
[PMID: 31257471]
[118]
Weiner, M.W.; Sadowsky, C.; Saxton, J.; Hofbauer, R.K.; Graham, S.M.; Yu, S.Y.; Li, S.; Hsu, H.A.; Suhy, J.; Fridman, M.; Perhach, J.L. Magnetic resonance imaging and neuropsychological results from a trial of memantine in Alzheimer’s disease. Alzheimers Dement., 2011, 7(4), 425-435.
[http://dx.doi.org/10.1016/j.jalz.2010.09.003] [PMID: 21646051]
[119]
Lopez, O.L.; Becker, J.T.; Wahed, A.S.; Saxton, J.; Sweet, R.A.; Wolk, D.A.; Klunk, W.; DeKosky, S.T. Long-term effects of the concomitant use of memantine with cholinesterase inhibition in Alzheimer disease. J. Neurol. Neurosurg. Psychiatry, 2009, 80(6), 600-607.
[http://dx.doi.org/10.1136/jnnp.2008.158964] [PMID: 19204022]
[120]
Grossberg, G.; Manes, F.; Allegri, R.; Gutierrez, R.L.M.; Gloger, S.; Xie, L.; Jia, X.D.; Perhach, J.; Graham, S.M. P4‐405: A multinational, randomized, double‐blind, placebo‐controlled, parallel‐ group trial of memantine extended‐release capsule (28 mg, once daily) in patients with moderate to severe Alzheimer’s disease. Alzheimers Dement., 2008, 4(4S_Part_24), T793.
[http://dx.doi.org/10.1016/j.jalz.2008.05.2476]
[121]
Thomas, S.J.; Grossberg, G.T. Memantine: A review of studies into its safety and efficacy in treating Alzheimer’s disease and other dementias. Clin. Interv. Aging, 2009, 4, 367-377.
[PMID: 19851512]
[122]
Porsteinsson, A.; Grossberg, G.; Mintzer, J.; Olin, J. 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.
[http://dx.doi.org/10.2174/156720508783884576] [PMID: 18288936]
[123]
Atri, A.; Shaughnessy, L.W.; Locascio, J.J.; Growdon, J.H. Long-term course and effectiveness of combination therapy in Alzheimer disease. Alzheimer Dis. Assoc. Disord., 2008, 22(3), 209-221.
[http://dx.doi.org/10.1097/WAD.0b013e31816653bc] [PMID: 18580597]
[124]
Cummings, J.L.; Schneider, E.; Tariot, P.N.; Graham, S.M. Behavioral effects of memantine in Alzheimer disease patients receiving donepezil treatment. Neurology, 2006, 67(1), 57-63.
[http://dx.doi.org/10.1212/01.wnl.0000223333.42368.f1] [PMID: 16832078]
[125]
Feldman, H.H.; Schmitt, F.A.; Olin, J.T. Activities of daily living in moderate-to-severe Alzheimer disease: An analysis of the treatment effects of memantine in patients receiving stable donepezil treatment. Alzheimer Dis. Assoc. Disord., 2006, 20(4), 263-268.
[http://dx.doi.org/10.1097/01.wad.0000213859.35355.59] [PMID: 17132971]
[126]
Schmitt, F.A.; Van Dyck, C.H.; Wichems, C.H.; Olin, J.T. Cognitive response to memantine in moderate to severe Alzheimer disease patients already receiving donepezil: An exploratory reanalysis. Alzheimer Dis. Assoc. Disord., 2006, 20(4), 255-262.
[http://dx.doi.org/10.1097/01.wad.0000213860.35355.d4] [PMID: 17132970]
[127]
Tariot, P.N.; Farlow, M.R.; Grossberg, G.T.; Graham, S.M.; McDonald, S.; Gergel, I. Memantine treatment in patients with moderate to severe Alzheimer’s disease already receiving donepezil: A randomized controlled trial. JAMA, 2004, 291(3), 317-324.
[http://dx.doi.org/10.1001/jama.291.3.317] [PMID: 14734594]
[128]
Choi, S.H.; Park, K.W.; Na, D.L.; Han, H.J.; Kim, E.J.; Shim, Y.S.; Lee, J.H. 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.
[http://dx.doi.org/10.1185/03007995.2011.582484] [PMID: 21561398]
[129]
Riepe, M.W.; Adler, G.; Ibach, B.; Weinkauf, B.; Tracik, F.; Gunay, I. Domain-specific improvement of cognition on memantine in patients with Alzheimer’s disease treated with rivastigmine. Dement. Geriatr. Cogn. Disord., 2007, 23(5), 301-306.
[http://dx.doi.org/10.1159/000100875] [PMID: 17356273]
[130]
Dantoine, T.; Auriacombe, S.; Sarazin, M.; Becker, H.; Pere, J.J.; Bourdeix, I. Rivastigmine monotherapy and combination therapy with memantine in patients with moderately severe Alzheimer’s disease who failed to benefit from previous cholinesterase inhibitor treatment. Int. J. Clin. Pract., 2006, 60(1), 110-118.
[http://dx.doi.org/10.1111/j.1368-5031.2005.00769.x] [PMID: 16409439]
[131]
Farlow, M.R.; Alva, G.; Meng, X.; Olin, J.T. A 25-week, open-label trial investigating rivastigmine transdermal patches with concomitant memantine in mild-to-moderate Alzheimer’s disease: A post hoc analysis. Curr. Med. Res. Opin., 2010, 26(2), 263-269.
[http://dx.doi.org/10.1185/03007990903434914] [PMID: 19929593]
[132]
Salloway, S.; Sperling, R.; Gilman, S.; Fox, N.C.; Blennow, K.; Raskind, M.; Sabbagh, M.; Honig, L.S.; Doody, R.; van Dyck, C.H.; Mulnard, R.; Barakos, J.; Gregg, K.M.; Liu, E.; Lieberburg, I.; Schenk, D.; Black, R.; Grundman, M. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology, 2009, 73(24), 2061-2070.
[http://dx.doi.org/10.1212/WNL.0b013e3181c67808] [PMID: 19923550]
[133]
Rinne, J.O.; Brooks, D.J.; Rossor, M.N.; Fox, N.C.; Bullock, R.; Klunk, W.E.; Mathis, C.A.; Blennow, K.; Barakos, J.; Okello, A.A. de LIano, S.R.M.; Liu, E.; Koller, M.; Gregg, K.M.; Schenk, D.; Black, R.; Grundman, M. 11C-PiB PET assessment of change in fibrillar amyloid-β load in patients with Alzheimer’s disease treated with bapineuzumab: A phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol., 2010, 9(4), 363-372.
[http://dx.doi.org/10.1016/S1474-4422(10)70043-0] [PMID: 20189881]
[134]
Sperling, R.; Salloway, S.; Brooks, D.J.; Tampieri, D.; Barakos, J.; Fox, N.C.; Raskind, M.; Sabbagh, M.; Honig, L.S.; Porsteinsson, A.P.; Lieberburg, I.; Arrighi, H.M.; Morris, K.A.; Lu, Y.; Liu, E.; Gregg, K.M.; Brashear, H.R.; Kinney, G.G.; Black, R.; Grundman, M. Amyloid-related imaging abnormalities in patients with Alzheimer’s disease treated with bapineuzumab: A retrospective analysis. Lancet Neurol., 2012, 11(3), 241-249.
[http://dx.doi.org/10.1016/S1474-4422(12)70015-7] [PMID: 22305802]
[135]
Fettelschoss, A.; Zabel, F.; Bachmann, M.F. Vaccination against Alzheimer disease. Hum. Vaccin. Immunother., 2014, 10(4), 847-851.
[http://dx.doi.org/10.4161/hv.28183] [PMID: 24535580]
[136]
Holmes, C.; Boche, D.; Wilkinson, D.; Yadegarfar, G.; Hopkins, V.; Bayer, A.; Jones, R.W.; Bullock, R.; Love, S.; Neal, J.W.; Zotova, E.; Nicoll, J.A.R. Long-term effects of Aβ42 immunisation in Alzheimer’s disease: Follow-up of a randomised, placebo-controlled phase I trial. Lancet, 2008, 372(9634), 216-223.
[http://dx.doi.org/10.1016/S0140-6736(08)61075-2] [PMID: 18640458]
[137]
Vellas, B.; Black, R.; Thal, L.; Fox, N.; Daniels, M.; McLennan, G.; Tompkins, C.; Leibman, C.; Pomfret, M.; Grundman, M. Long-term follow-up of patients immunized with AN1792: Reduced functional decline in antibody responders. Curr. Alzheimer Res., 2009, 6(2), 144-151.
[http://dx.doi.org/10.2174/156720509787602852] [PMID: 19355849]
[138]
Klaver, A.C.; Finke, J.M.; Digambaranath, J.; Balasubramaniam, M.; Loeffler, D.A. Antibody concentrations to Aβ1–42 monomer and soluble oligomers in untreated and antibody–antigen-dissociated intravenous immunoglobulin preparations. Int. Immunopharmacol., 2010, 10(1), 115-119.
[http://dx.doi.org/10.1016/j.intimp.2009.10.005] [PMID: 19840873]
[139]
Relkin, N.R.; Szabo, P.; Adamiak, B.; Burgut, T.; Monthe, C.; Lent, R.W.; Younkin, S.; Younkin, L.; Schiff, R.; Weksler, M.E. 18-Month study of intravenous immunoglobulin for treatment of mild Alzheimer’s disease. Neurobiol. Aging, 2009, 30(11), 1728-1736.
[http://dx.doi.org/10.1016/j.neurobiolaging.2007.12.021] [PMID: 18294736]
[140]
Vellas, B.; Sol, O.; Snyder, P.J.; Ousset, P.J.; Haddad, R.; Maurin, M.; Lemarié, J-C.; Désiré, L.; Pando, M.P. EHT0202 in Alzheimer’s disease: A 3-month, randomized, placebo-controlled, double-blind study. Curr. Alzheimer Res., 2011, 8(2), 203-212.
[http://dx.doi.org/10.2174/156720511795256053] [PMID: 21222604]
[141]
Harrington, C.; Sawchak, S.; Chiang, C.; Davies, J.; Donovan, C.; Saunders, A.M.; Irizarry, M.; Jeter, B.; Zvartau, H.M.; Van Dyck, C.H.; Gold, M. Rosiglitazone does not improve cognition or global function when used as adjunctive therapy to AChE inhibitors in mild-to-moderate Alzheimer’s disease: Two phase 3 studies. Curr. Alzheimer Res., 2011, 8(5), 592-606.
[http://dx.doi.org/10.2174/156720511796391935] [PMID: 21592048]
[142]
Feldman, H.H.; Doody, R.S.; Kivipelto, M.; Sparks, D.L.; Waters, D.D.; Jones, R.W.; Schwam, E.; Schindler, R.; Hey, H.J.; DeMicco, D.A.; Breazna, A. Randomized controlled trial of atorvastatin in mild to moderate Alzheimer’s disease: LEADe. Neurology, 2010, 74(12), 956-964.
[http://dx.doi.org/10.1212/WNL.0b013e3181d6476a] [PMID: 20200346]
[143]
Sano, M.; Bell, K.L.; Galasko, D.; Galvin, J.E.; Thomas, R.G.; Van Dyck, C.H.; Aisen, P.S. A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease. Neurology, 2011, 77(6), 556-563.
[http://dx.doi.org/10.1212/WNL.0b013e318228bf11] [PMID: 21795660]
[144]
Green, R.C.; Schneider, L.S.; Amato, D.A.; Beelen, A.P.; Wilcock, G.; Swabb, E.A.; Zavitz, K.H. Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: A randomized controlled trial. JAMA, 2009, 302(23), 2557-2564.
[http://dx.doi.org/10.1001/jama.2009.1866] [PMID: 20009055]
[145]
Wilcock, G.K.; Black, S.E.; Hendrix, S.B.; Zavitz, K.H.; Swabb, E.A.; Laughlin, M.A. Efficacy and safety of tarenflurbil in mild to moderate Alzheimer’s disease: A randomised phase II trial. Lancet Neurol., 2008, 7(6), 483-493.
[http://dx.doi.org/10.1016/S1474-4422(08)70090-5] [PMID: 18450517]
[146]
Rigaud, A.S.; André, G.; Vellas, B.; Touchon, J.; Pere, J.J. No additional benefit of HRT on response to rivastigmine in menopausal women with AD. Neurology, 2003, 60(1), 148-149.
[http://dx.doi.org/10.1212/WNL.60.1.148-a] [PMID: 12525745]
[147]
Aisen, P.S.; Gauthier, S.; Ferris, S.H.; Saumier, D.; Haine, D.; Garceau, D.; Duong, A.; Suhy, J.; Oh, J.; Lau, W.C.; Sampalis, J. Tramiprosate in mild-to-moderate Alzheimer’s disease – A randomized, double-blind, placebo-controlled, multi-centre study (the Alphase Study). Arch. Med. Sci., 2011, 1(1), 102-111.
[http://dx.doi.org/10.5114/aoms.2011.20612] [PMID: 22291741]
[148]
Gauthier, S.; Aisen, P.S.; Ferris, S.H.; Saumier, D.; Duong, A.; Haine, D.; Garceau, D.; Suhy, J.; Oh, J.; Lau, W.; Sampalis, J. Effect of tramiprosate in patients with mild-to-moderate alzheimer’s disease: Exploratory analyses of the MRI sub-group of the alphase study. J. Nutr. Health Aging, 2009, 13(6), 550-557.
[http://dx.doi.org/10.1007/s12603-009-0106-x] [PMID: 19536424]
[149]
Salloway, S.; Sperling, R.; Keren, R.; Porsteinsson, A.P.; van Dyck, C.H.; Tariot, P.N.; Gilman, S.; Arnold, D.; Abushakra, S.; Hernandez, C.; Crans, G.; Liang, E.; Quinn, G.; Bairu, M.; Pastrak, A.; Cedarbaum, J.M. A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease. Neurology, 2011, 77(13), 1253-1262.
[http://dx.doi.org/10.1212/WNL.0b013e3182309fa5] [PMID: 21917766]
[150]
Lannfelt, L.; Blennow, K.; Zetterberg, H.; Batsman, S.; Ames, D.; Harrison, J.; Masters, C.L.; Targum, S.; Bush, A.I.; Murdoch, R.; Wilson, J.; Ritchie, C.W. Safety, efficacy, and biomarker findings of PBT2 in targeting Aβ as a modifying therapy for Alzheimer’s disease: A phase IIa, double-blind, randomised, placebo-controlled trial. Lancet Neurol., 2008, 7(9), 779-786.
[http://dx.doi.org/10.1016/S1474-4422(08)70167-4] [PMID: 18672400]
[151]
A study of semagacestat for Alzheimer’s patients (Identity XT). NCT01035138 2022. Available from: https://clinicaltrials.gov/ct2/show/NCT01035138 (Accessed on: 21 April 2022).
[152]
Fleisher, A.S.; Raman, R.; Siemers, E.R.; Becerra, L.; Clark, C.M.; Dean, R.A.; Farlow, M.R.; Galvin, J.E.; Peskind, E.R.; Quinn, J.F.; Sherzai, A.; Sowell, B.B.; Aisen, P.S.; Thal, L.J. Phase 2 safety trial targeting amyloid beta production with a gamma-secretase inhibitor in Alzheimer disease. Arch. Neurol., 2008, 65(8), 1031-1038.
[http://dx.doi.org/10.1001/archneur.65.8.1031] [PMID: 18695053]
[153]
Henley, D.B.; May, P.C.; Dean, R.A.; Siemers, E.R. Development of semagacestat (LY450139), a functional γ-secretase inhibitor, for the treatment of Alzheimer’s disease. Expert Opin. Pharmacother., 2009, 10(10), 1657-1664.
[http://dx.doi.org/10.1517/14656560903044982] [PMID: 19527190]

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