Strategies for Treatment of Disease-Associated Dementia Beyond Alzheimer's
Disease: An Update

Sabiya   Samim   Khan; Gopal   L.   Khatik; Ashok   K.   Datusalia
doi:10.2174/1570159X20666220411083922
Abstract

Memory, cognition, dementia, and neurodegeneration are complexly interlinked processes with various mechanistic pathways, leading to a range of clinical outcomes. They are strongly associated with pathological conditions like Alzheimer’s disease, Parkinson’s disease, schizophrenia, and stroke and are a growing concern for their timely diagnosis and management. Several cognitionenhancing interventions for management include non-pharmacological interventions like diet, exercise, and physical activity, while pharmacological interventions include medicinal agents, herbal agents, and nutritional supplements. This review critically analyzed and discussed the currently available agents under different drug development phases designed to target the molecular targets, including cholinergic receptor, glutamatergic system, GABAergic targets, glycine site, serotonergic targets, histamine receptors, etc. Understanding memory formation and pathways involved therein aids in opening the new gateways to treating cognitive disorders. However, clinical studies suggest that there is still a dearth of knowledge about the pathological mechanism involved in neurological conditions, making the dropouts of agents from the initial phases of the clinical trial. Hence, a better understanding of the disease biology, mode of drug action, and interlinked mechanistic pathways at a molecular level is required.
Keywords: Dementia, Cognitive disorders, Neurodegeneration, Alzheimer’s disease, Parkinson’s disease, Schizophrenia
« Previous Next »
Graphical Abstract

[1]
Arlt, S. Non-Alzheimer’s disease-related memory impairment and dementia. Dialogues Clin. Neurosci.,  2013, 15(4), 465-473.
 [http://dx.doi.org/10.31887/DCNS.2013.15.4/sarlt] [PMID:  24459413]

[2]
Iadecola, C.; Duering, M.; Hachinski, V.; Joutel, A.; Pendlebury, S.T.; Schneider, J.A.; Dichgans, M. Vascular cognitive impairment and dementia: JACC scientific expert panel. J. Am. Coll. Cardiol.,  2019, 73(25), 3326-3344.
 [http://dx.doi.org/10.1016/j.jacc.2019.04.034] [PMID:  31248555]

[3]
McKhann, G.; Drachman, D.; Folstein, M.; Katzman, R.; Price, D.; Stadlan, E.M. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology,  1984, 34(7), 939-944.
 [http://dx.doi.org/10.1212/WNL.34.7.939] [PMID:  6610841]

[4]
Landrø, N.I. Memory function in schizophrenia. Acta Psychiatr. Scand. Suppl.,  1994, 384, 87-94.
 [http://dx.doi.org/10.1111/j.1600-0447.1994.tb05896.x] [PMID:  7879649]

[5]
Kaul, M.; Garden, G.A.; Lipton, S.A. Pathways to neuronal injury and apoptosis in HIV-associated dementia. Nature,  2001, 410(6831), 988-994.
 [http://dx.doi.org/10.1038/35073667] [PMID:  11309629]

[6]
Ringman, J.M.; Cummings, J.L. Current and emerging pharmacological treatment options for dementia. Behav. Neurol.,  2006, 17(1), 5-16.
 [http://dx.doi.org/10.1155/2006/315386] [PMID:  16720956]

[7]
Petersen, R.C.; Caracciolo, B.; Brayne, C.; Gauthier, S.; Jelic, V.; Fratiglioni, L. Mild cognitive impairment: a concept in evolution. J. Intern. Med.,  2014, 275(3), 214-228.
 [http://dx.doi.org/10.1111/joim.12190] [PMID:  24605806]

[8]
Ljubenkov, P.A.; Geschwind, M.D. Dementia. Semin. Neurol.,  2016, 36(4), 397-404.
 [http://dx.doi.org/10.1055/s-0036-1585096] [PMID:  27643909]

[9]
Griesbach, G.S.; Hovda, D.A.; Gomez-Pinilla, F. Exercise-induced improvement in cognitive performance after traumatic brain injury in rats is dependent on BDNF activation. Brain Res.,  2009, 1288, 105-115.
 [http://dx.doi.org/10.1016/j.brainres.2009.06.045] [PMID:  19555673]

[10]
Das, A.; Shanker, G.; Nath, C.; Pal, R.; Singh, S.; Singh, H. A comparative study in rodents of standardized extracts of Bacopa monniera and Ginkgo biloba: anticholinesterase and cognitive enhancing activities. Pharmacol. Biochem. Behav.,  2002, 73(4), 893-900.
 [http://dx.doi.org/10.1016/S0091-3057(02)00940-1] [PMID:  12213536]

[11]
Romay, M.C.; Toro, C.; Iruela-Arispe, M.L. Emerging molecular mechanisms of vascular dementia. Curr. Opin. Hematol.,  2019, 26(3), 199-206.
 [http://dx.doi.org/10.1097/MOH.0000000000000502] [PMID:  30883434]

[12]
Söderström, I.; Strand, M.; Ingridsson, A.C.; Nasic, S.; Olsson, T. 17beta-estradiol and enriched environment accelerate cognitive recovery after focal brain ischemia. Eur. J. Neurosci.,  2009, 29(6), 1215-1224.
 [http://dx.doi.org/10.1111/j.1460-9568.2009.06662.x] [PMID:  19302156]

[13]
Liu, Z.; Fan, Y.; Won, S.J.; Neumann, M.; Hu, D.; Zhou, L.; Weinstein, P.R.; Liu, J. Chronic treatment with minocycline preserves adult new neurons and reduces functional impairment after focal cerebral ischemia. Stroke,  2007, 38(1), 146-152.
 [http://dx.doi.org/10.1161/01.STR.0000251791.64910.cd] [PMID:  17122429]

[14]
Esneault, E.; Castagne, V.; Moser, P.; Bonny, C.; Bernaudin, M. D-JNKi, a peptide inhibitor of c-Jun N-terminal kinase, promotes functional recovery after transient focal cerebral ischemia in rats. Neuroscience,  2008, 152(2), 308-320.
 [http://dx.doi.org/10.1016/j.neuroscience.2007.12.036] [PMID:  18262367]

[15]
Ma, B.; Li, M.; Nong, H.; Shi, J.; Liu, G.; Zhang, J. Protective effects of extract of Coeloglossum viride var. bracteatum on ischemia-induced neuronal death and cognitive impairment in rats. Behav. Pharmacol.,  2008, 19(4), 325-333.
 [PMID:  18622180]

[16]
Sun, M.K.; Alkon, D.L. Synergistic effects of chronic bryostatin-1 and alpha-tocopherol on spatial learning and memory in rats. Eur. J. Pharmacol.,  2008, 584(2-3), 328-337.
 [http://dx.doi.org/10.1016/j.ejphar.2008.02.014] [PMID:  18313045]

[17]
Kauppinen, T.M.; Suh, S.W.; Berman, A.E.; Hamby, A.M.; Swanson, R.A. Inhibition of poly(ADP-ribose) polymerase suppresses inflammation and promotes recovery after ischemic injury. J. Cereb. Blood Flow Metab.,  2009, 29(4), 820-829.
 [http://dx.doi.org/10.1038/jcbfm.2009.9] [PMID:  19190653]

[18]
Huang, L.; He, Z.; Guo, L.; Wang, H. Improvement of cognitive deficit and neuronal damage in rats with chronic cerebral ischemia via relative long-term inhibition of rho-kinase. Cell. Mol. Neurobiol.,  2008, 28(5), 757-768.
 [http://dx.doi.org/10.1007/s10571-007-9157-x] [PMID:  17554619]

[19]
Williams-Gray, C.H.; Foltynie, T.; Brayne, C.E.; Robbins, T.W.; Barker, R.A. Evolution of cognitive dysfunction in an incident Parkinson’s disease cohort. Brain,  2007, 130(Pt 7), 1787-1798.
 [http://dx.doi.org/10.1093/brain/awm111] [PMID:  17535834]

[20]
Bronnick, K.; Emre, M.; Lane, R.; Tekin, S.; Aarsland, D. Profile of cognitive impairment in dementia associated with Parkinson’s disease compared with Alzheimer’s disease. J. Neurol. Neurosurg. Psychiatry,  2007, 78(10), 1064-1068.
 [http://dx.doi.org/10.1136/jnnp.2006.108076] [PMID:  17287236]

[21]
Buter, T.C.; van den Hout, A.; Matthews, F.E.; Larsen, J.P.; Brayne, C.; Aarsland, D. Dementia and survival in Parkinson disease: a 12-year population study. Neurology,  2008, 70(13), 1017-1022.
 [http://dx.doi.org/10.1212/01.wnl.0000306632.43729.24] [PMID:  18362281]

[22]
Williams-Gray, C.H.; Foltynie, T.; Lewis, S.J.; Barker, R.A. Cognitive deficits and psychosis in Parkinson’s disease: a review of pathophysiology and therapeutic options. CNS Drugs,  2006, 20(6), 477-505.
 [http://dx.doi.org/10.2165/00023210-200620060-00004] [PMID:  16734499]

[23]
Galvin, J.E.; Pollack, J.; Morris, J.C. Clinical phenotype of Parkinson disease dementia. Neurology,  2006, 67(9), 1605-1611.
 [http://dx.doi.org/10.1212/01.wnl.0000242630.52203.8f] [PMID:  17101891]

[24]
Rongve, A.; Aarsland, D. Management of Parkinson’s disease dementia: practical considerations. Drugs Aging,  2006, 23(10), 807-822.
 [http://dx.doi.org/10.2165/00002512-200623100-00004] [PMID:  17067184]

[25]
Nieoullon, A. Dopamine and the regulation of cognition and attention. Prog. Neurobiol.,  2002, 67(1), 53-83.
 [http://dx.doi.org/10.1016/S0301-0082(02)00011-4] [PMID:  12126656]

[26]
Brown, L.L.; Schneider, J.S.; Lidsky, T.I. Sensory and cognitive functions of the basal ganglia. Curr. Opin. Neurobiol.,  1997, 7(2), 157-163.
 [http://dx.doi.org/10.1016/S0959-4388(97)80003-7] [PMID:  9142758]

[27]
Israel, Z.; Bergman, H. Pathophysiology of the basal ganglia and movement disorders: from animal models to human clinical applications. Neurosci. Biobehav. Rev.,  2008, 32(3), 367-377.
 [http://dx.doi.org/10.1016/j.neubiorev.2007.08.005] [PMID:  17949812]

[28]
Leyden, J.; Kleinig, T. The role of the basal ganglia in data processing. Med. Hypotheses,  2008, 71(1), 61-64.
 [http://dx.doi.org/10.1016/j.mehy.2008.02.013] [PMID:  18410994]

[29]
Emre, M. Dementia associated with Parkinson’s disease. Lancet Neurol.,  2003, 2(4), 229-237.
 [http://dx.doi.org/10.1016/S1474-4422(03)00351-X] [PMID:  12849211]

[30]
Emre, M.; Aarsland, D.; Albanese, A.; Byrne, E.J.; Deuschl, G.; De Deyn, P.P.; Durif, F.; Kulisevsky, J.; van Laar, T.; Lees, A.; Poewe, W.; Robillard, A.; Rosa, M.M.; Wolters, E.; Quarg, P.; Tekin, S.; Lane, R. Rivastigmine for dementia associated with Parkinson’s disease. N. Engl. J. Med.,  2004, 351(24), 2509-2518.
 [http://dx.doi.org/10.1056/NEJMoa041470] [PMID:  15590953]

[31]
Moretti, R.; Torre, P.; Vilotti, C.; Antonello, R.M.; Pizzolato, G. Rivastigmine and Parkinson dementia complex. Expert Opin. Pharmacother.,  2007, 8(6), 817-829.
 [http://dx.doi.org/10.1517/14656566.8.6.817] [PMID:  17425477]

[32]
Werber, E.A.; Rabey, J.M. The beneficial effect of cholinesterase inhibitors on patients suffering from Parkinson’s disease and dementia. J. Neural Transm. (Vienna),  2001, 108(11), 1319-1325.
 [http://dx.doi.org/10.1007/s007020100008] [PMID:  11768630]

[33]
Aarsland, D.; Hutchinson, M.; Larsen, J.P. Cognitive, psychiatric and motor response to galantamine in Parkinson’s disease with dementia. Int. J. Geriatr. Psychiatry,  2003, 18(10), 937-941.
 [http://dx.doi.org/10.1002/gps.949] [PMID:  14533126]

[34]
Cummings, J.L. Cholinesterase inhibitors for treatment of dementia associated with Parkinson’s disease. J. Neurol. Neurosurg. Psychiatry,  2005, 76(7), 903-904.
 [http://dx.doi.org/10.1136/jnnp.2004.061499] [PMID:  15965192]

[35]
Shohamy, D.; Myers, C.E.; Geghman, K.D.; Sage, J.; Gluck, M.A. L-dopa impairs learning, but spares generalization, in Parkinson’s disease. Neuropsychologia,  2006, 44(5), 774-784.
 [http://dx.doi.org/10.1016/j.neuropsychologia.2005.07.013] [PMID:  16150469]

[36]
Singh, N.; Pillay, V.; Choonara, Y.E. Advances in the treatment of Parkinson’s disease. Prog. Neurobiol.,  2007, 81(1), 29-44.
 [http://dx.doi.org/10.1016/j.pneurobio.2006.11.009] [PMID:  17258379]

[37]
Mendez, M.F. What is the Relationship of Traumatic Brain Injury to Dementia? J. Alzheimers Dis.,  2017, 57(3), 667-681.
 [http://dx.doi.org/10.3233/JAD-161002] [PMID:  28269777]

[38]
Parga, B.A.; Logsdon, A.F.; Banks, W.A.; Ransom, C.B. Traumatic Brain Injury Broadly Affects GABAergic Signaling in Dentate Gyrus Granule Cells. eNeuro,  2021, 8(3), ENEURO.0055-20.2021..
 [http://dx.doi.org/10.1523/ENEURO.0055-20.2021] [PMID: 33514602]

[39]
Carron, S.F.; Yan, E.B.; Alwis, D.S.; Rajan, R. Differential susceptibility of cortical and subcortical inhibitory neurons and astrocytes in the long term following diffuse traumatic brain injury. J. Comp. Neurol.,  2016, 524(17), 3530-3560.
 [http://dx.doi.org/10.1002/cne.24014] [PMID:  27072754]

[40]
Yan, H.; Feng, Y.; Wang, Q. Altered Effective Connectivity of Hippocampus-Dependent Episodic Memory Network in mTBI Survivors. Neural Plast.,  2016, 2016, 6353845.
 [http://dx.doi.org/10.1155/2016/6353845] [PMID:  28074162]

[41]
Biswas, C. Marković D.; Giza, C.C. Alterations in mesoscopic oscillations affecting episodic memory following developmental traumatic brain injury. Exp. Neurol.,  2018, 300, 259-273.
 [http://dx.doi.org/10.1016/j.expneurol.2017.10.021] [PMID:  29066322]

[42]
Paterno, R.; Folweiler, K.A.; Cohen, A.S. Pathophysiology and treatment of memory dysfunction after traumatic brain injury. Curr. Neurol. Neurosci. Rep.,  2017, 17(7), 52.
 [http://dx.doi.org/10.1007/s11910-017-0762-x] [PMID:  28500417]

[43]
Langa, K.M.; Foster, N.L.; Larson, E.B. Mixed dementia: emerging concepts and therapeutic implications. JAMA,  2004, 292(23), 2901-2908.
 [http://dx.doi.org/10.1001/jama.292.23.2901] [PMID:  15598922]

[44]
Custodio, N.; Montesinos, R.; Lira, D.; Herrera-Pérez, E.; Bardales, Y.; Valeriano-Lorenzo, L. Mixed dementia: A review of the evidence. Dement. Neuropsychol.,  2017, 11(4), 364-370.
 [http://dx.doi.org/10.1590/1980-57642016dn11-040005] [PMID:  29354216]

[45]
Fierini, F. Mixed dementia: Neglected clinical entity or nosographic artifice? J. Neurol. Sci.,  2020, 410, 116662.
 [http://dx.doi.org/10.1016/j.jns.2019.116662] [PMID:  31911281]

[46]
Bhidayasiri, R. Atypical dementia: when it is not Alzheimer’s disease. J. Med. Assoc. Thai.,  2007, 90(10), 2222-2232.
 [PMID:  18041446]

[47]
Tsai, R.M.; Boxer, A.L. Therapy and clinical trials in frontotemporal dementia: past, present, and future. J. Neurochem.,  2016, 138(Suppl. 1), 211-221.
 [http://dx.doi.org/10.1111/jnc.13640] [PMID:  27306957]

[48]
Mulkey, M. Understanding Frontotemporal Disease Progression and Management Strategies. Nurs. Clin. North Am.,  2019, 54(3), 437-448.
 [http://dx.doi.org/10.1016/j.cnur.2019.04.011] [PMID:  31331629]

[49]
Cipriani, G.; Danti, S.; Nuti, A.; Di Fiorino, M.; Cammisuli, D.M. Is that schizophrenia or frontotemporal dementia? Supporting clinicians in making the right diagnosis. Acta Neurol. Belg.,  2020, 120(4), 799-804.
 [http://dx.doi.org/10.1007/s13760-020-01352-z] [PMID:  32314269]

[50]
Harciarek, M.; Malaspina, D.; Sun, T.; Goldberg, E. Schizophrenia and frontotemporal dementia: shared causation? Int. Rev. Psychiatry,  2013, 25(2), 168-177.
 [http://dx.doi.org/10.3109/09540261.2013.765389] [PMID:  23611347]

[51]
Uehara, T.; Sumiyoshi, T.; Kurachi, M. New pharmacotherapy targeting cognitive dysfunction of schizophrenia via modulation of GABA neuronal function. Curr. Neuropharmacol.,  2015, 13(6), 793-801.
 [http://dx.doi.org/10.2174/1570159X13666151009120153] [PMID:  26630957]

[52]
Cooper, J.J.; Ovsiew, F. The relationship between schizophrenia and frontotemporal dementia. J. Geriatr. Psychiatry Neurol.,  2013, 26(3), 131-137.
 [http://dx.doi.org/10.1177/0891988713490992] [PMID:  23733854]

[53]
Eggers, C.; Arendt, G.; Hahn, K.; Husstedt, I.W.; Maschke, M.; Neuen-Jacob, E.; Obermann, M.; Rosenkranz, T.; Schielke, E.; Straube, E. HIV-1-associated neurocognitive disorder: epidemiology, pathogenesis, diagnosis, and treatment. J. Neurol.,  2017, 264(8), 1715-1727.
 [http://dx.doi.org/10.1007/s00415-017-8503-2] [PMID:  28567537]

[54]
Wang, Y.; Liu, M.; Lu, Q.; Farrell, M.; Lappin, J.M.; Shi, J.; Lu, L.; Bao, Y. Global prevalence and burden of HIV-associated neurocognitive disorder: A meta-analysis. Neurology,  2020, 95(19), e2610-e2621.
 [http://dx.doi.org/10.1212/WNL.0000000000010752] [PMID:  32887786]

[55]
Lindl, K.A.; Marks, D.R.; Kolson, D.L.; Jordan-Sciutto, K.L. HIV-associated neurocognitive disorder: pathogenesis and therapeutic opportunities. J. Neuroimmune Pharmacol.,  2010, 5(3), 294-309.
 [http://dx.doi.org/10.1007/s11481-010-9205-z] [PMID:  20396973]

[56]
Ambrosius, B.; Gold, R.; Chan, A.; Faissner, S. Antineuroinflammatory drugs in HIV-associated neurocognitive disorders as potential therapy. Neurol. Neuroimmunol. Neuroinflamm.,  2019, 6(3), e551.
 [http://dx.doi.org/10.1212/NXI.0000000000000551] [PMID:  31119186]

[57]
Bennett, S.; Thomas, A.J. Depression and dementia: cause, consequence or coincidence? Maturitas,  2014, 79(2), 184-190.
 [http://dx.doi.org/10.1016/j.maturitas.2014.05.009] [PMID:  24931304]

[58]
Black, S.; Kraemer, K.; Shah, A.; Simpson, G.; Scogin, F.; Smith, A. Diabetes, depression, and cognition: A recursive cycle of cognitive dysfunction and glycemic dysregulation. Curr. Diab. Rep.,  2018, 18(11), 118.
 [http://dx.doi.org/10.1007/s11892-018-1079-0] [PMID:  30267224]

[59]
van Sloten, T.T.; Sedaghat, S.; Carnethon, M.R.; Launer, L.J.; Stehouwer, C.D.A. Cerebral microvascular complications of type 2 diabetes: stroke, cognitive dysfunction, and depression. Lancet Diabetes Endocrinol.,  2020, 8(4), 325-336.
 [http://dx.doi.org/10.1016/S2213-8587(19)30405-X] [PMID:  32135131]

[60]
Livingston, G.A.; Sax, K.B.; McClenahan, Z.; Blumenthal, E.; Foley, K.; Willison, J.; Mann, A.H.; James, I.M.; Acetyl, L. Carnitine in dementia. Int. J. Geriatr. Psychiatry,  1991, 6(12), 853-860.
 [http://dx.doi.org/10.1002/gps.930061205]

[61]
Rampello, L.; Giammona, G.; Aleppo, G.; Favit, A.; Fiore, L. Trophic action of acetyl-L-carnitine in neuronal cultures. Acta Neurol. (Napoli),  1992, 14(1), 15-21.
 [PMID:  1580200]

[62]
Pedata, F.; Giovannelli, L.; Spignoli, G.; Giovannini, M.G.; Pepeu, G. Phosphatidylserine increases acetylcholine release from cortical slices in aged rats. Neurobiol. Aging,  1985, 6(4), 337-339.
 [http://dx.doi.org/10.1016/0197-4580(85)90013-2] [PMID:  4088427]

[63]
Hashioka, S.; Han, Y.H.; Fujii, S.; Kato, T.; Monji, A.; Utsumi, H.; Sawada, M.; Nakanishi, H.; Kanba, S. Phosphatidylserine and phosphatidylcholine-containing liposomes inhibit amyloid beta and interferon-gamma-induced microglial activation. Free Radic. Biol. Med.,  2007, 42(7), 945-954.
 [http://dx.doi.org/10.1016/j.freeradbiomed.2006.12.003] [PMID:  17349923]

[64]
Holmquist, L.; Stuchbury, G.; Berbaum, K.; Muscat, S.; Young, S.; Hager, K.; Engel, J.; Münch, G. Lipoic acid as a novel treatment for Alzheimer’s disease and related dementias. Pharmacol. Ther.,  2007, 113(1), 154-164.
 [http://dx.doi.org/10.1016/j.pharmthera.2006.07.001] [PMID:  16989905]

[65]
Beal, M.F. Mitochondrial dysfunction and oxidative damage in Alzheimer’s and Parkinson’s diseases and coenzyme Q10 as a potential treatment. J. Bioenerg. Biomembr.,  2004, 36(4), 381-386.
 [http://dx.doi.org/10.1023/B:JOBB.0000041772.74810.92] [PMID:  15377876]

[66]
Hashimoto, M.; Hossain, S.; Shimada, T.; Sugioka, K.; Yamasaki, H.; Fujii, Y.; Ishibashi, Y.; Oka, J.; Shido, O. Docosahexaenoic acid provides protection from impairment of learning ability in Alzheimer’s disease model rats. J. Neurochem.,  2002, 81(5), 1084-1091.
 [http://dx.doi.org/10.1046/j.1471-4159.2002.00905.x] [PMID:  12065621]

[67]
Tucker, K.L.; Qiao, N.; Scott, T.; Rosenberg, I.; Spiro, A. III High homocysteine and low B vitamins predict cognitive decline in aging men: the veterans affairs normative aging study. Am. J. Clin. Nutr.,  2005, 82(3), 627-635.
 [http://dx.doi.org/10.1093/ajcn/82.3.627] [PMID:  16155277]

[68]
Aiguo , Wu Zhe Ying; Gomez-Pinilla, F. Vitamin E protects against oxidative damage and learning disability after mild traumatic brain injury in rats. Neurorehabil. Neural Repair,  2010, 24(3), 290-298.
 [http://dx.doi.org/10.1177/1545968309348318] [PMID:  19841436]

[69]
Cummings, J.; Aisen, P.; Lemere, C.; Atri, A.; Sabbagh, M.; Salloway, S. Aducanumab produced a clinically meaningful benefit in association with amyloid lowering. Alzheimers Res. Ther.,  2021, 13(1), 98.
 [http://dx.doi.org/10.1186/s13195-021-00838-z] [PMID:  33971962]

[70]
Tolar, M.; Abushakra, S.; Hey, J.A.; Porsteinsson, A.; Sabbagh, M. Aducanumab, gantenerumab, BAN2401, and ALZ-801-the first wave of amyloid-targeting drugs for Alzheimer’s disease with potential for near term approval. Alzheimers Res. Ther.,  2020, 12(1), 95.
 [http://dx.doi.org/10.1186/s13195-020-00663-w] [PMID:  32787971]

[71]
Jean-Louis, G.; von Gizycki, H.; Zizi, F. Melatonin effects on sleep, mood, and cognition in elderly with mild cognitive impairment. J. Pineal Res.,  1998, 25(3), 177-183.
 [http://dx.doi.org/10.1111/j.1600-079X.1998.tb00557.x] [PMID:  9745987]

[72]
Bitner, R.S.; Bunnelle, W.H.; Anderson, D.J.; Briggs, C.A.; Buccafusco, J.; Curzon, P.; Decker, M.W.; Frost, J.M.; Gronlien, J.H.; Gubbins, E.; Li, J.; Malysz, J.; Markosyan, S.; Marsh, K.; Meyer, M.D.; Nikkel, A.L.; Radek, R.J.; Robb, H.M.; Timmermann, D.; Sullivan, J.P.; Gopalakrishnan, M. Broad-spectrum efficacy across cognitive domains by alpha7 nicotinic acetylcholine receptor agonism correlates with activation of ERK1/2 and CREB phosphorylation pathways. J. Neurosci.,  2007, 27(39), 10578-10587.
 [http://dx.doi.org/10.1523/JNEUROSCI.2444-07.2007] [PMID:  17898229]

[73]
Arendash, G.W.; Schleif, W.; Rezai-Zadeh, K.; Jackson, E.K.; Zacharia, L.C.; Cracchiolo, J.R.; Shippy, D.; Tan, J. Caffeine protects Alzheimer’s mice against cognitive impairment and reduces brain beta-amyloid production. Neuroscience,  2006, 142(4), 941-952.
 [http://dx.doi.org/10.1016/j.neuroscience.2006.07.021] [PMID:  16938404]

[74]
Minzenberg, M.J.; Carter, C.S. Modafinil: a review of neurochemical actions and effects on cognition. Neuropsychopharmacology,  2008, 33(7), 1477-1502.
 [http://dx.doi.org/10.1038/sj.npp.1301534] [PMID:  17712350]

[75]
Giacobini, E.; Spiegel, R.; Enz, A.; Veroff, A.E.; Cutler, N.R. Inhibition of acetyl- and butyryl-cholinesterase in the cerebrospinal fluid of patients with Alzheimer’s disease by rivastigmine: correlation with cognitive benefit. J. Neural Transm. (Vienna),  2002, 109(7-8), 1053-1065.
 [http://dx.doi.org/10.1007/s007020200089] [PMID:  12111443]

[76]
Narahashi, T.; Moriguchi, S.; Zhao, X.; Marszalec, W.; Yeh, J.Z. Mechanisms of action of cognitive enhancers on neuroreceptors. Biol. Pharm. Bull.,  2004, 27(11), 1701-1706.
 [http://dx.doi.org/10.1248/bpb.27.1701] [PMID:  15516710]

[77]
Balsters, J.H.; O’Connell, R.G.; Martin, M.P.; Galli, A.; Cassidy, S.M.; Kilcullen, S.M.; Delmonte, S.; Brennan, S.; Meaney, J.F.; Fagan, A.J.; Bokde, A.L.; Upton, N.; Lai, R.; Laruelle, M.; Lawlor, B.; Robertson, I.H. Donepezil impairs memory in healthy older subjects: behavioural, EEG and simultaneous EEG/fMRI biomarkers. PLoS One,  2011, 6(9), e24126.
 [http://dx.doi.org/10.1371/journal.pone.0024126] [PMID:  21931653]

[78]
Dunbar, G.; Boeijinga, P.H.; Demazières, A.; Cisterni, C.; Kuchibhatla, R.; Wesnes, K.; Luthringer, R. Effects of TC-1734 (AZD3480), a selective neuronal nicotinic receptor agonist, on cognitive performance and the EEG of young healthy male volunteers. Psychopharmacology (Berl.),  2007, 191(4), 919-929.
 [http://dx.doi.org/10.1007/s00213-006-0675-x] [PMID:  17225162]

[79]
Zoladz, P.R.; Campbell, A.M.; Park, C.R.; Schaefer, D.; Danysz, W.; Diamond, D.M. Enhancement of long-term spatial memory in adult rats by the noncompetitive NMDA receptor antagonists, memantine and neramexane. Pharmacol. Biochem. Behav.,  2006, 85(2), 298-306.
 [http://dx.doi.org/10.1016/j.pbb.2006.08.011] [PMID:  17045636]

[80]
Tzavara, E.T.; Bymaster, F.P.; Overshiner, C.D.; Davis, R.J.; Perry, K.W.; Wolff, M.; McKinzie, D.L.; Witkin, J.M.; Nomikos, G.G. Procholinergic and memory enhancing properties of the selective norepinephrine uptake inhibitor atomoxetine. Mol. Psychiatry,  2006, 11(2), 187-195.
 [http://dx.doi.org/10.1038/sj.mp.4001763] [PMID:  16231039]

[81]
Winblad, B. Piracetam: a review of pharmacological properties and clinical uses. CNS Drug Rev.,  2005, 11(2), 169-182.
 [http://dx.doi.org/10.1111/j.1527-3458.2005.tb00268.x] [PMID:  16007238]

[82]
Moriguchi, S.; Shioda, N.; Han, F.; Narahashi, T.; Fukunaga, K. CaM kinase II and protein kinase C activations mediate enhancement of long-term potentiation by nefiracetam in the rat hippocampal CA1 region. J. Neurochem.,  2008, 106(3), 1092-1103.
 [http://dx.doi.org/10.1111/j.1471-4159.2008.05440.x] [PMID:  18445137]

[83]
Gong, B.; Vitolo, O.V.; Trinchese, F.; Liu, S.; Shelanski, M.; Arancio, O. Persistent improvement in synaptic and cognitive functions in an Alzheimer mouse model after rolipram treatment. J. Clin. Invest.,  2004, 114(11), 1624-1634.
 [http://dx.doi.org/10.1172/JCI22831] [PMID:  15578094]

[84]
Onur, O.A.; Schlaepfer, T.E.; Kukolja, J.; Bauer, A.; Jeung, H.; Patin, A.; Otte, D.M.; Shah, N.J.; Maier, W.; Kendrick, K.M.; Fink, G.R.; Hurlemann, R. The N-methyl-D-aspartate receptor co-agonist D-cycloserine facilitates declarative learning and hippocampal activity in humans. Biol. Psychiatry,  2010, 67(12), 1205-1211.
 [http://dx.doi.org/10.1016/j.biopsych.2010.01.022] [PMID:  20303474]

[85]
Monleón, S.; Vinader-Caerols, C.; Arenas, M.C.; Parra, A. Antidepressant drugs and memory: insights from animal studies. Eur. Neuropsychopharmacol.,  2008, 18(4), 235-248.
 [http://dx.doi.org/10.1016/j.euroneuro.2007.07.001] [PMID:  17761406]

[86]
Avery, R.A.; Franowicz, J.S.; Studholme, C.; van Dyck, C.H.; Arnsten, A.F. The alpha-2A-adrenoceptor agonist, guanfacine, increases regional cerebral blood flow in dorsolateral prefrontal cortex of monkeys performing a spatial working memory task. Neuropsychopharmacology,  2000, 23(3), 240-249.
 [http://dx.doi.org/10.1016/S0893-133X(00)00111-1] [PMID:  10942848]

[87]
Liljequist, R.; Haapalinna, A.; Ahlander, M.; Li, Y.H.; Männistö, P.T. Catechol O-methyltransferase inhibitor tolcapone has minor influence on performance in experimental memory models in rats. Behav. Brain Res.,  1997, 82(2), 195-202.
 [http://dx.doi.org/10.1016/S0166-4328(97)80989-8] [PMID:  9030401]

[88]
Emmenegger, H.; Meier-Ruge, W. The actions of Hydergine on the brain. A histochemical, circulatory and neurophysiological study. Pharmacology,  1968, 1(1), 65-78.
 [http://dx.doi.org/10.1159/000135946] [PMID:  4969614]

[89]
Markstein, R. Hydergine: interaction with the neurotransmitter systems in the central nervous system. J. Pharmacol.,  1985, 16(Suppl. 3), 1-17.
 [http://dx.doi.org/10.1007/978-1-4612-5058-6_30] [PMID:  2869188]

[90]
Bennett, G.W.; Ballard, T.M.; Watson, C.D.; Fone, K.C. Effect of neuropeptides on cognitive function. Exp. Gerontol.,  1997, 32(4-5), 451-469.
 [http://dx.doi.org/10.1016/S0531-5565(96)00159-3] [PMID:  9315449]

[91]
Hindmarch, I.; Coleston, D.M.; Kerr, J.S. Psychopharmacological effects of pyritinol in normal volunteers. Neuropsychobiology,  1991, 24(3), 159-164.
 [http://dx.doi.org/10.1159/000119478] [PMID:  2135070]

[92]
Levkovitz, Y.; Arnest, G.; Mendlovic, S.; Treves, I.; Fennig, S. The effect of Ondansetron on memory in schizophrenic patients. Brain Res. Bull.,  2005, 65(4), 291-295.
 [http://dx.doi.org/10.1016/j.brainresbull.2003.09.022] [PMID:  15811593]

[93]
Fioravanti, M.; Flicker, L. Efficacy of nicergoline in dementia and other age associated forms of cognitive impairment. Cochrane Database Syst. Rev.,  2001, (4), CD003159.
 [PMID:  11687175]

[94]
Stancheva, S.L.; Alova, L.G. Effect of centrophenoxine, piracetam and aniracetam on the monoamine oxidase activity in different brain structures of rats. Farmakol. Toksikol.,  1988, 51(3), 16-18.
 [PMID:  3137089]

[95]
Steele, T.D.; Hodges, D.B., Jr; Levesque, T.R.; Locke, K.W.; Sandage, B.W., Jr The D1 agonist dihydrexidine releases acetylcholine and improves cognition in rats. Ann. N. Y. Acad. Sci.,  1996, 777(1), 427-430.
 [http://dx.doi.org/10.1111/j.1749-6632.1996.tb34457.x] [PMID:  8624125]

[96]
Woolley, M.L.; Waters, K.A.; Reavill, C.; Bull, S.; Lacroix, L.P.; Martyn, A.J.; Hutcheson, D.M.; Valerio, E.; Bate, S.; Jones, D.N.C.; Dawson, L.A. Selective dopamine D4 receptor agonist (A-412997) improves cognitive performance and stimulates motor activity without influencing reward-related behaviour in rat. Behav. Pharmacol.,  2008, 19(8), 765-776.
 [http://dx.doi.org/10.1097/FBP.0b013e32831c3b06] [PMID:  19020411]

[97]
Roozendaal, B.; Quirarte, G.L.; McGaugh, J.L. Glucocorticoids interact with the basolateral amygdala beta-adrenoceptor--cAMP/cAMP/PKA system in influencing memory consolidation. Eur. J. Neurosci.,  2002, 15(3), 553-560.
 [http://dx.doi.org/10.1046/j.0953-816x.2001.01876.x] [PMID:  11876783]

[98]
Takasaki, K.; Uchida, K.; Fujikawa, R.; Nogami, A.; Nakamura, K.; Kawasaki, C.; Yamaguchi, K.; Morita, M.; Morishita, K.; Kubota, K.; Katsurabayashi, S.; Mishima, K.; Fujiwara, M.; Iwasaki, K. Neuroprotective effects of citidine-5-diphosphocholine on impaired spatial memory in a rat model of cerebrovascular dementia. J. Pharmacol. Sci.,  2011, 116(2), 232-237.
 [http://dx.doi.org/10.1254/jphs.11013FP] [PMID:  21613753]

[99]
Echeverria, V.; Zeitlin, R.; Burgess, S.; Patel, S.; Barman, A.; Thakur, G.; Mamcarz, M.; Wang, L.; Sattelle, D.B.; Kirschner, D.A.; Mori, T.; Leblanc, R.M.; Prabhakar, R.; Arendash, G.W. Cotinine reduces amyloid-β aggregation and improves memory in Alzheimer’s disease mice. J. Alzheimers Dis.,  2011, 24(4), 817-835.
 [http://dx.doi.org/10.3233/JAD-2011-102136] [PMID:  21321389]

[100]
Hamani, C.; McAndrews, M.P.; Cohn, M.; Oh, M.; Zumsteg, D.; Shapiro, C.M.; Wennberg, R.A.; Lozano, A.M. Memory enhancement induced by hypothalamic/fornix deep brain stimulation. Ann. Neurol.,  2008, 63(1), 119-123.
 [http://dx.doi.org/10.1002/ana.21295] [PMID:  18232017]

[101]
Hampel, H.; Toschi, N.; Babiloni, C.; Baldacci, F.; Black, K.L.; Bokde, A.L.W.; Bun, R.S.; Cacciola, F.; Cavedo, E.; Chiesa, P.A.; Colliot, O.; Coman, C.M.; Dubois, B.; Duggento, A.; Durrleman, S.; Ferretti, M.T.; George, N.; Genthon, R.; Habert, M.O.; Herholz, K.; Koronyo, Y.; Koronyo-Hamaoui, M.; Lamari, F.; Langevin, T.; Lehéricy, S.; Lorenceau, J.; Neri, C.; Nisticò, R.; Nyasse-Messene, F.; Ritchie, C.; Rossi, S.; Santarnecchi, E.; Sporns, O.; Verdooner, S.R.; Vergallo, A.; Villain, N.; Younesi, E.; Garaci, F.; Lista, S. Revolution of Alzheimer precision neurology. passageway of systems biology and neurophysiology. J. Alzheimers Dis.,  2018, 64(s1), S47-S105.
 [http://dx.doi.org/10.3233/JAD-179932] [PMID:  29562524]

[102]
Ferreira-Vieira, T.H.; Guimaraes, I.M.; Silva, F.R.; Ribeiro, F.M. Alzheimer’s disease: Targeting the Cholinergic System. Curr. Neuropharmacol.,  2016, 14(1), 101-115.
 [http://dx.doi.org/10.2174/1570159X13666150716165726] [PMID:  26813123]

[103]
Stip, E.; Chouinard, S.; Boulay, L.J. On the trail of a cognitive enhancer for the treatment of schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2005, 29(2), 219-232.
 [http://dx.doi.org/10.1016/j.pnpbp.2004.11.004] [PMID:  15694228]

[104]
Rollema, H.; Hajós, M.; Seymour, P.A.; Kozak, R.; Majchrzak, M.J.; Guanowsky, V.; Horner, W.E.; Chapin, D.S.; Hoffmann, W.E.; Johnson, D.E.; McLean, S.; Freeman, J.; Williams, K.E. Preclinical pharmacology of the alpha4beta2 nAChR partial agonist varenicline related to effects on reward, mood and cognition. Biochem. Pharmacol.,  2009, 78(7), 813-824.
 [http://dx.doi.org/10.1016/j.bcp.2009.05.033] [PMID:  19501054]

[105]
Thomsen, M.S.; Hansen, H.H.; Timmerman, D.B.; Mikkelsen, J.D. Cognitive improvement by activation of alpha7 nicotinic acetylcholine receptors: from animal models to human pathophysiology. Curr. Pharm. Des.,  2010, 16(3), 323-343.
 [http://dx.doi.org/10.2174/138161210790170094] [PMID:  20109142]

[106]
Roncarati, R.; Scali, C.; Comery, T.A.; Grauer, S.M.; Aschmi, S.; Bothmann, H.; Jow, B.; Kowal, D.; Gianfriddo, M.; Kelley, C.; Zanelli, U.; Ghiron, C.; Haydar, S.; Dunlop, J.; Terstappen, G.C. Procognitive and neuroprotective activity of a novel alpha7 nicotinic acetylcholine receptor agonist for treatment of neurodegenerative and cognitive disorders. J. Pharmacol. Exp. Ther.,  2009, 329(2), 459-468.
 [http://dx.doi.org/10.1124/jpet.108.150094] [PMID:  19223665]

[107]
Martin, L.F.; Kem, W.R.; Freedman, R. Alpha-7 nicotinic receptor agonists: potential new candidates for the treatment of schizophrenia. Psychopharmacology (Berl.),  2004, 174(1), 54-64.
 [http://dx.doi.org/10.1007/s00213-003-1750-1] [PMID:  15205879]

[108]
Wallace, T.L.; Ballard, T.M.; Pouzet, B.; Riedel, W.J.; Wettstein, J.G. Drug targets for cognitive enhancement in neuropsychiatric disorders. Pharmacol. Biochem. Behav.,  2011, 99(2), 130-145.
 [http://dx.doi.org/10.1016/j.pbb.2011.03.022] [PMID:  21463652]

[109]
Schuster, R.M.; Pachas, G.N.; Stoeckel, L.; Cather, C.; Nadal, M.; Mischoulon, D.; Schoenfeld, D.A.; Zhang, H.; Ulysse, C.; Dodds, E.B.; Sobolewski, S.; Hudziak, V.; Hanly, A.; Fava, M.; Evins, A.E. Phase IIb trial of an α7 nicotinic receptor partial agonist with and without nicotine patch for withdrawal-associated cognitive deficits and tobacco abstinence. J. Clin. Psychopharmacol.,  2018, 38(4), 307-316.
 [http://dx.doi.org/10.1097/JCP.0000000000000919] [PMID:  29912798]

[110]
Bar-Am, O.; Weinreb, O.; Amit, T.; Youdim, M.B. 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]

[111]
Maurice, T. Protection by sigma-1 receptor agonists is synergic with donepezil, but not with memantine, in a mouse model of amyloid-induced memory impairments. Behav. Brain Res.,  2016, 296, 270-278.
 [http://dx.doi.org/10.1016/j.bbr.2015.09.020] [PMID:  26386305]

[112]
Reggiani, A.M.; Simoni, E.; Caporaso, R.; Meunier, J.; Keller, E.; Maurice, T.; Minarini, A.; Rosini, M.; Cavalli, A. In vivo characterization of ARN14140, a memantine/galantamine-based multi-target compound for Alzheimer’s disease. Sci. Rep.,  2016, 6(1), 33172.
 [http://dx.doi.org/10.1038/srep33172] [PMID:  27609215]

[113]
Takata, K.; Amamiya, T.; Mizoguchi, H.; Kawanishi, S.; Kuroda, E.; Kitamura, R.; Ito, A.; Saito, Y.; Tawa, M.; Nagasawa, T.; Okamoto, H.; Sugino, Y.; Takegami, S.; Kitade, T.; Toda, Y.; Kem, W.R.; Kitamura, Y.; Shimohama, S.; Ashihara, E. Alpha7 nicotinic acetylcholine receptor-specific agonist DMXBA (GTS-21) attenuates Aβ accumulation through suppression of neuronal γ-secretase activity and promotion of microglial amyloid-β phagocytosis and ameliorates cognitive impairment in a mouse model of Alzheimer’s disease. Neurobiol. Aging,  2018, 62, 197-209.
 [http://dx.doi.org/10.1016/j.neurobiolaging.2017.10.021] [PMID:  29175709]

[114]
Medeiros, R. Castello, N.A.; Cheng, D.; Kitazawa, M.; Baglietto-Vargas, D.; Green, K.N.; Esbenshade, T.A.; Bitner, R.S.; Decker, M.W.; LaFerla, F.M. α7 Nicotinic receptor agonist enhances cognition in aged 3xTg-AD mice with robust plaques and tangles. Am. J. Pathol.,  2014, 184(2), 520-529.
 [http://dx.doi.org/10.1016/j.ajpath.2013.10.010] [PMID:  24269557]

[115]
Sadigh-Eteghad, S.; Talebi, M.; Mahmoudi, J.; Babri, S.; Shanehbandi, D. Selective activation of α7 nicotinic acetylcholine receptor by PHA-543613 improves Aβ25-35-mediated cognitive deficits in mice. Neuroscience,  2015, 298, 81-93.
 [http://dx.doi.org/10.1016/j.neuroscience.2015.04.017] [PMID:  25881725]

[116]
King, D.; Iwuagwu, C.; Cook, J.; McDonald, I.M.; Mate, R.; Zusi, F.C.; Hill, M.D.; Fang, H.; Zhao, R.; Wang, B.; Easton, A.E.; Miller, R.; Post-Munson, D.; Knox, R.J.; Gallagher, L.; Westphal, R.; Molski, T.; Fan, J.; Clarke, W.; Benitex, Y.; Lentz, K.A.; Denton, R.; Morgan, D.; Zaczek, R.; Lodge, N.J.; Bristow, L.J.; Macor, J.E.; Olson, R.E. BMS-933043, a Selective α7 nAChR partial agonist for the treatment of cognitive deficits associated with schizophrenia. ACS Med. Chem. Lett.,  2017, 8(3), 366-371.
 [http://dx.doi.org/10.1021/acsmedchemlett.7b00032] [PMID:  28337332]

[117]
Krintel, C.; Harpsøe, K.; Zachariassen, L.G.; Peters, D.; Frydenvang, K.; Pickering, D.S.; Gajhede, M.; Kastrup, J.S. Structural analysis of the positive AMPA receptor modulators CX516 and Me-CX516 in complex with the GluA2 ligand-binding domain. Acta Crystallogr. D Biol. Crystallogr.,  2013, 69(Pt 9), 1645-1652.
 [http://dx.doi.org/10.1107/S0907444913011839] [PMID:  23999288]

[118]
Tatsukawa, T.; Raveau, M.; Ogiwara, I.; Hattori, S.; Miyamoto, H.; Mazaki, E.; Itohara, S.; Miyakawa, T.; Montal, M.; Yamakawa, K. Scn2a haploinsufficient mice display a spectrum of phenotypes affecting anxiety, sociability, memory flexibility and ampakine CX516 rescues their hyperactivity. Mol. Autism,  2019, 10, 15.
 [http://dx.doi.org/10.1186/s13229-019-0265-5] [PMID:  30962870]

[119]
Trzepacz, P.T.; Cummings, J.; Konechnik, T.; Forrester, T.D.; Chang, C.; Dennehy, E.B.; Willis, B.A.; Shuler, C.; Tabas, L.B.; Lyketsos, C. Mibampator (LY451395) randomized clinical trial for agitation/aggression in Alzheimer’s disease. Int. Psychogeriatr.,  2013, 25(5), 707-719.
 [http://dx.doi.org/10.1017/S1041610212002141] [PMID:  23257314]

[120]
Xiao, D.; Xie, F.; Xu, X.; Zhou, X. The impact and mechanism of ampakine CX1739 on protection against respiratory depression in rats. Future Med. Chem.,  2020, 12(23), 2093-2104.
 [http://dx.doi.org/10.4155/fmc-2020-0256] [PMID:  33030058]

[121]
Yefimenko, N.; Portero-Tresserra, M.; Martí-Nicolovius, M.; Guillazo-Blanch, G.; Vale-Martínez, A. The AMPA receptor modulator S18986 in the prelimbic cortex enhances acquisition and retention of an odor-reward association. Neurosci. Lett.,  2013, 548, 105-109.
 [http://dx.doi.org/10.1016/j.neulet.2013.05.032] [PMID:  23707650]

[122]
Liu, W.; Jiang, X.; Zu, Y.; Yang, Y.; Liu, Y.; Sun, X.; Xu, Z.; Ding, H.; Zhao, Q. A comprehensive description of GluN2B-selective N-methyl-D-aspartate (NMDA) receptor antagonists. Eur. J. Med. Chem.,  2020, 200, 112447.
 [http://dx.doi.org/10.1016/j.ejmech.2020.112447] [PMID:  32450321]

[123]
Ayala, J.E.; Chen, Y.; Banko, J.L.; Sheffler, D.J.; Williams, R.; Telk, A.N.; Watson, N.L.; Xiang, Z.; Zhang, Y.; Jones, P.J.; Lindsley, C.W.; Olive, M.F.; Conn, P.J. mGluR5 positive allosteric modulators facilitate both hippocampal LTP and LTD and enhance spatial learning. Neuropsychopharmacology,  2009, 34(9), 2057-2071.
 [http://dx.doi.org/10.1038/npp.2009.30] [PMID:  19295507]

[124]
Umbricht, D.; Niggli, M.; Sanwald-Ducray, P.; Deptula, D.; Moore, R.; Grünbauer, W.; Boak, L.; Fontoura, P.  Randomized, double-blind, placebo-controlled trial of the mGlu2/3 negative allosteric modulator decoglurant in partially refractory major depressive disorder. J. Clin. Psychiatry.,  2020, 81(4), 18m12470.
 [http://dx.doi.org/10.4088/JCP.18m12470] [PMID: 32663909]

[125]
Collinson, N.; Atack, J.R.; Laughton, P.; Dawson, G.R.; Stephens, D.N. An inverse agonist selective for alpha5 subunit-containing GABAA receptors improves encoding and recall but not consolidation in the Morris water maze. Psychopharmacology (Berl.),  2006, 188(4), 619-628.
 [http://dx.doi.org/10.1007/s00213-006-0361-z] [PMID:  16633803]

[126]
King, M.V.; Marsden, C.A.; Fone, K.C.F. A role for the 5-HT(1A), 5-HT4 and 5-HT6 receptors in learning and memory. Trends Pharmacol. Sci.,  2008, 29(9), 482-492.
 [http://dx.doi.org/10.1016/j.tips.2008.07.001] [PMID:  19086256]

[127]
Marszalek-Grabska, M.; Gibula-Bruzda, E.; Bodzon-Kulakowska, A.; Suder, P.; Gawel, K.; Talarek, S.; Listos, J.; Kedzierska, E.; Danysz, W.; Kotlinska, J.H. ADX-47273, a mGlu5 receptor positive allosteric modulator, attenuates deficits in cognitive flexibility induced by withdrawal from ‘binge-like’ ethanol exposure in rats. Behav. Brain Res.,  2018, 338, 9-16.
 [http://dx.doi.org/10.1016/j.bbr.2017.10.007] [PMID:  29030082]

[128]
Ho, Y.J.; Ho, S.C.; Pawlak, C.R.; Yeh, K.Y. Effects of D-cycloserine on MPTP-induced behavioral and neurological changes: potential for treatment of Parkinson’s disease dementia. Behav. Brain Res.,  2011, 219(2), 280-290.
 [http://dx.doi.org/10.1016/j.bbr.2011.01.028] [PMID:  21262271]

[129]
Lidö, H.H.; Jonsson, S.; Hyytiä, P.; Ericson, M.; Söderpalm, B. Further characterization of the GlyT-1 inhibitor Org25935: anti-alcohol, neurobehavioral, and gene expression effects. J. Neural Transm. (Vienna),  2017, 124(5), 607-619.
 [http://dx.doi.org/10.1007/s00702-017-1685-z] [PMID:  28161754]

[130]
D’Souza, D.C.; Carson, R.E.; Driesen, N.; Johannesen, J.; Ranganathan, M.; Krystal, J.H.; Yale Gly, T.S.G. Dose-related target occupancy and effects on circuitry, behavior, and neuroplasticity of the glycine transporter-1 inhibitor PF-03463275 in healthy and schizophrenia subjects. Biol. Psychiatry,  2018, 84(6), 413-421.
 [http://dx.doi.org/10.1016/j.biopsych.2017.12.019] [PMID:  29499855]

[131]
Dunayevich, E.; Buchanan, R.W.; Chen, C.Y.; Yang, J.; Nilsen, J.; Dietrich, J.M.; Sun, H.; Marder, S. Efficacy and safety of the glycine transporter type-1 inhibitor AMG 747 for the treatment of negative symptoms associated with schizophrenia. Schizophr. Res.,  2017, 182, 90-97.
 [http://dx.doi.org/10.1016/j.schres.2016.10.027] [PMID:  27789188]

[132]
Vogel, K.R.; Pearl, P.L.; Theodore, W.H.; McCarter, R.C.; Jakobs, C.; Gibson, K.M. Thirty years beyond discovery--clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. J. Inherit. Metab. Dis.,  2013, 36(3), 401-410.
 [http://dx.doi.org/10.1007/s10545-012-9499-5] [PMID:  22739941]

[133]
Schwam, E.M.; Nicholas, T.; Chew, R.; Billing, C.B.; Davidson, W.; Ambrose, D.; Altstiel, L.D. A multicenter, double-blind, placebo-controlled trial of the PDE9A inhibitor, PF-04447943, in Alzheimer’s disease. Curr. Alzheimer Res.,  2014, 11(5), 413-421.
 [http://dx.doi.org/10.2174/1567205011666140505100858] [PMID:  24801218]

[134]
McHutchison, C.; Blair, G.W.; Appleton, J.P.; Chappell, F.M.; Doubal, F.; Bath, P.M.; Wardlaw, J.M. Cilostazol for Secondary Prevention of Stroke and Cognitive Decline: Systematic Review and Meta-Analysis. Stroke,  2020, 51(8), 2374-2385.
 [http://dx.doi.org/10.1161/STROKEAHA.120.029454] [PMID:  32646330]

[135]
Motta, N.A.V.; Autran, L.J.; Brazão, S.C.; Lopes, R.O.; Scaramello, C.B.V.; Lima, G.F.; Brito, F.C.F. Could cilostazol be beneficial in COVID-19 treatment? Thinking about phosphodiesterase-3 as a therapeutic target. Int. Immunopharmacol.,  2021, 92, 107336.
 [http://dx.doi.org/10.1016/j.intimp.2020.107336] [PMID:  33418248]

[136]
Shen, F.; Smith, J.A.; Chang, R.; Bourdet, D.L.; Tsuruda, P.R.; Obedencio, G.P.; Beattie, D.T. 5-HT(4) receptor agonist mediated enhancement of cognitive function in vivo and amyloid precursor protein processing in vitro: A pharmacodynamic and pharmacokinetic assessment. Neuropharmacology,  2011, 61(1-2), 69-79.
 [http://dx.doi.org/10.1016/j.neuropharm.2011.02.026] [PMID:  21392515]

[137]
Millan, M.J.; Dekeyne, A.; Gobert, A.; Brocco, M.; Mannoury la Cour, C.; Ortuno, J.C.; Watson, D.; Fone, K.C.F. Dual-acting agents for improving cognition and real-world function in Alzheimer’s disease: Focus on 5-HT6 and D3 receptors as hubs. Neuropharmacology,  2020, 177, 108099.
 [http://dx.doi.org/10.1016/j.neuropharm.2020.108099] [PMID:  32525060]

[138]
Xu, F.; Zhang, G.; Yin, J.; Zhang, Q.; Ge, M.Y.; Peng, L.; Wang, S.; Li, Y. Fluoxetine mitigating late-stage cognition and neurobehavior impairment induced by cerebral ischemia reperfusion injury through inhibiting ERS-mediated neurons apoptosis in the hippocampus. Behav. Brain Res.,  2019, 370, 111952.
 [http://dx.doi.org/10.1016/j.bbr.2019.111952] [PMID:  31103751]

[139]
Coric, V.; Salloway, S.; van Dyck, C.H.; Dubois, B.; Andreasen, N.; Brody, M.; Curtis, C.; Soininen, H.; Thein, S.; Shiovitz, T.; Pilcher, G.; Ferris, S.; Colby, S.; Kerselaers, W.; Dockens, R.; Soares, H.; Kaplita, S.; Luo, F.; Pachai, C.; Bracoud, L.; Mintun, M.; Grill, J.D.; Marek, K.; Seibyl, J.; Cedarbaum, J.M.; Albright, C.; Feldman, H.H.; Berman, R.M. Targeting prodromal alzheimer disease with avagacestat: a randomized clinical trial. JAMA Neurol.,  2015, 72(11), 1324-1333.
 [http://dx.doi.org/10.1001/jamaneurol.2015.0607] [PMID:  26414022]

[140]
Gómez-Revuelta, M.; Pelayo-Terán, J.M.; Juncal-Ruiz, M.; Ortiz-García de la Foz, V.; Vázquez-Bourgon, J.; González-Pinto, A.; Crespo-Facorro, B. Long-Term Antipsychotic Effectiveness in First Episode of Psychosis: A 3-Year Follow-Up Randomized Clinical Trial Comparing Aripiprazole, Quetiapine, and Ziprasidone. Int. J. Neuropsychopharmacol.,  2018, 21(12), 1090-1101.
 [http://dx.doi.org/10.1093/ijnp/pyy082] [PMID:  30215723]

[141]
Frampton, J.E. Brexpiprazole: A Review in Schizophrenia. Drugs,  2019, 79(2), 189-200.
 [http://dx.doi.org/10.1007/s40265-019-1052-5] [PMID:  30671869]

[142]
Watanabe, Y.; Yamada, S.; Otsubo, T.; Kikuchi, T. Brexpiprazole for the Treatment of Schizophrenia in Adults: An Overview of Its Clinical Efficacy and Safety and a Psychiatrist’s Perspective. Drug Des. Devel. Ther.,  2020, 14, 5559-5574.
 [http://dx.doi.org/10.2147/DDDT.S240859] [PMID:  33376301]

[143]
Han, D.; Shi, S.; Luo, H. The therapeutic effect of quetiapine on cognitive impairment associated with 5-HT1A presynaptic receptor involved schizophrenia. J. Integr. Neurosci.,  2019, 18(3), 245-251.
 [http://dx.doi.org/10.31083/j.jin.2019.03.186] [PMID:  31601072]

[144]
He, J.; Luo, H.; Yan, B.; Yu, Y.; Wang, H.; Wei, Z.; Zhang, Y.; Xu, H.; Tempier, A.; Li, X.; Li, X.M. Beneficial effects of quetiapine in a transgenic mouse model of Alzheimer’s disease. Neurobiol. Aging,  2009, 30(8), 1205-1216.
 [http://dx.doi.org/10.1016/j.neurobiolaging.2007.11.001] [PMID:  18079026]

[145]
Schechter, L.E.; Smith, D.L.; Rosenzweig-Lipson, S.; Sukoff, S.J.; Dawson, L.A.; Marquis, K.; Jones, D.; Piesla, M.; Andree, T.; Nawoschik, S.; Harder, J.A.; Womack, M.D.; Buccafusco, J.; Terry, A.V.; Hoebel, B.; Rada, P.; Kelly, M.; Abou-Gharbia, M.; Barrett, J.E.; Childers, W. Lecozotan (SRA-333): a selective serotonin 1A receptor antagonist that enhances the stimulated release of glutamate and acetylcholine in the hippocampus and possesses cognitive-enhancing properties. J. Pharmacol. Exp. Ther.,  2005, 314(3), 1274-1289.
 [http://dx.doi.org/10.1124/jpet.105.086363] [PMID:  15951399]

[146]
Labie, C.; Lafon, C.; Marmouget, C.; Saubusse, P.; Fournier, J.; Keane, P.E.; Le Fur, G.; Soubrié, P. Effect of the neuroprotective compound SR57746A on nerve growth factor synthesis in cultured astrocytes from neonatal rat cortex. Br. J. Pharmacol.,  1999, 127(1), 139-144.
 [http://dx.doi.org/10.1038/sj.bjp.0702545] [PMID:  10369466]

[147]
Komater, V.A.; Buckley, M.J.; Browman, K.E.; Pan, J.B.; Hancock, A.A.; Decker, M.W.; Fox, G.B. Effects of histamine H3 receptor antagonists in two models of spatial learning. Behav. Brain Res.,  2005, 159(2), 295-300.
 [http://dx.doi.org/10.1016/j.bbr.2004.11.008] [PMID:  15817192]

[148]
Egan, M.; Yaari, R.; Liu, L.; Ryan, M.; Peng, Y.; Lines, C.; Michelson, D. Pilot randomized controlled study of a histamine receptor inverse agonist in the symptomatic treatment of AD. Curr. Alzheimer Res.,  2012, 9(4), 481-490.
 [http://dx.doi.org/10.2174/156720512800492530] [PMID:  22272611]

[149]
Ivachtchenko, A.V.; Lavrovsky, Y.; Okun, I. AVN-101: A multi-target drug candidate for the treatment of CNS disorders. J. Alzheimers Dis.,  2016, 53(2), 583-620.
 [http://dx.doi.org/10.3233/JAD-151146] [PMID:  27232215]

[150]
Alrabiah, H. Levetiracetam. Profiles Drug Subst. Excip. Relat. Methodol.,  2019, 44, 167-204.
 [http://dx.doi.org/10.1016/bs.podrm.2019.02.003] [PMID:  31029217]

[151]
Hattori, N.; Takeda, A.; Takeda, S.; Nishimura, A.; Kitagawa, T.; Mochizuki, H.; Nagai, M.; Takahashi, R. Rasagiline monotherapy in early Parkinson’s disease: A phase 3, randomized study in Japan. Parkinsonism Relat. Disord.,  2019, 60, 146-152.
 [http://dx.doi.org/10.1016/j.parkreldis.2018.08.024] [PMID:  30205936]

[152]
Chang, Y.; Wang, L.B.; Li, D.; Lei, K.; Liu, S.Y. Efficacy of rasagiline for the treatment of Parkinson’s disease: an updated meta-analysis. Ann. Med.,  2017, 49(5), 421-434.
 [http://dx.doi.org/10.1080/07853890.2017.1293285] [PMID:  28293967]

[153]
Ross, J.; Sharma, S.; Winston, J.; Nunez, M.; Bottini, G.; Franceschi, M.; Scarpini, E.; Frigerio, E.; Fiorentini, F.; Fernandez, M.; Sivilia, S.; Giardino, L.; Calza, L.; Norris, D.; Cicirello, H.; Casula, D.; Imbimbo, B.P. CHF5074 reduces biomarkers of neuroinflammation in patients with mild cognitive impairment: a 12-week, double-blind, placebo-controlled study. Curr. Alzheimer Res.,  2013, 10(7), 742-753.
 [http://dx.doi.org/10.2174/13892037113149990144] [PMID:  23968157]

[154]
Ronsisvalle, N.; Di Benedetto, G.; Parenti, C.; Amoroso, S.; Bernardini, R.; Cantarella, G. CHF5074 protects SH-SY5Y human neuronal-like cells from amyloidbeta 25-35 and tumor necrosis factor related apoptosis inducing ligand toxicity in vitro. Curr. Alzheimer Res.,  2014, 11(7), 714-724.
 [http://dx.doi.org/10.2174/1567205011666140618104430] [PMID:  24938499]

[155]
Porrini, V.; Lanzillotta, A.; Branca, C.; Benarese, M.; Parrella, E.; Lorenzini, L.; Calzà, L.; Flaibani, R.; Spano, P.F.; Imbimbo, B.P.; Pizzi, M. CHF5074 (CSP-1103) induces microglia alternative activation in plaque-free Tg2576 mice and primary glial cultures exposed to beta-amyloid. Neuroscience,  2015, 302, 112-120.
 [http://dx.doi.org/10.1016/j.neuroscience.2014.10.029] [PMID:  25450955]

[156]
Gleason, C.E.; Fischer, B.L.; Dowling, N.M.; Setchell, K.D.; Atwood, C.S.; Carlsson, C.M.; Asthana, S. Cognitive effects of soy isoflavones in patients with Alzheimer’s disease. J. Alzheimers Dis.,  2015, 47(4), 1009-1019.
 [http://dx.doi.org/10.3233/JAD-142958] [PMID:  26401779]

[157]
Roozbeh, N.; Kashef, R.; Ghazanfarpour, M.; Kargarfard, L.; Darvish, L.; Khadivzadeh, T.; Dizavandi, F.R.; Afiat, M. Overview of the Effect of Herbal Medicines and Isoflavones on the Treatment of Cognitive Function. J. Menopausal Med.,  2018, 24(2), 113-118.
 [http://dx.doi.org/10.6118/jmm.2018.24.2.113] [PMID:  30202761]

[158]
Zhang, Z.; Zhang, B.; Wang, X.; Zhang, X.; Yang, Q.X.; Qing, Z.; Zhang, W.; Zhu, D.; Bi, Y. Olfactory dysfunction mediates adiposity in cognitive impairment of type 2 diabetes: Insights from clinical and functional neuroimaging studies. Diabetes Care,  2019, 42(7), 1274-1283.
 [http://dx.doi.org/10.2337/dc18-2584] [PMID:  31221697]

[159]
Li, J.; Deng, J.; Sheng, W.; Zuo, Z. Metformin attenuates Alzheimer’s disease-like neuropathology in obese, leptin-resistant mice. Pharmacol. Biochem. Behav.,  2012, 101(4), 564-574.
 [http://dx.doi.org/10.1016/j.pbb.2012.03.002] [PMID:  22425595]

[160]
Chou, P.S.; Ho, B.L.; Yang, Y.H. Effects of pioglitazone on the incidence of dementia in patients with diabetes. J. Diabetes Complications,  2017, 31(6), 1053-1057.
 [http://dx.doi.org/10.1016/j.jdiacomp.2017.01.006] [PMID:  28254448]

[161]
Tseng, C.H. Pioglitazone reduces dementia risk in patients with type 2 diabetes mellitus: A retrospective cohort analysis. J. Clin. Med.,  2018, 7(10), 310.
 [http://dx.doi.org/10.3390/jcm7100306] [PMID:  30262775]

[162]
Tseng, C.H. Dementia risk in type 2 diabetes patients: Acarbose use and its joint effects with metformin and pioglitazone. Aging Dis.,  2020, 11(3), 658-667.
 [http://dx.doi.org/10.14336/AD.2019.0621] [PMID:  32489710]

[163]
Harrington, C.; Sawchak, S.; Chiang, C.; Davies, J.; Donovan, C.; Saunders, A.M.; Irizarry, M.; Jeter, B.; Zvartau-Hind, 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]

[164]
Mullins, R.J.; Mustapic, M.; Chia, C.W.; Carlson, O.; Gulyani, S.; Tran, J.; Li, Y.; Mattson, M.P.; Resnick, S.; Egan, J.M.; Greig, N.H.; Kapogiannis, D. A pilot study of exenatide actions in Alzheimer’s disease. Curr. Alzheimer Res.,  2019, 16(8), 741-752.
 [http://dx.doi.org/10.2174/1567205016666190913155950] [PMID:  31518224]

[165]
An, J.; Zhou, Y.; Zhang, M.; Xie, Y.; Ke, S.; Liu, L.; Pan, X.; Chen, Z. Exenatide alleviates mitochondrial dysfunction and cognitive impairment in the 5×FAD mouse model of Alzheimer’s disease. Behav. Brain Res.,  2019, 370, 111932.
 [http://dx.doi.org/10.1016/j.bbr.2019.111932] [PMID:  31082410]

[166]
Femminella, G.D.; Frangou, E.; Love, S.B.; Busza, G.; Holmes, C.; Ritchie, C.; Lawrence, R.; McFarlane, B.; Tadros, G.; Ridha, B.H.; Bannister, C.; Walker, Z.; Archer, H.; Coulthard, E.; Underwood, B.R.; Prasanna, A.; Koranteng, P.; Karim, S.; Junaid, K.; McGuinness, B.; Nilforooshan, R.; Macharouthu, A.; Donaldson, A.; Thacker, S.; Russell, G.; Malik, N.; Mate, V.; Knight, L.; Kshemendran, S.; Harrison, J.; Hölscher, C.; Brooks, D.J.; Passmore, A.P.; Ballard, C.; Edison, P. Evaluating the effects of the novel GLP-1 analogue liraglutide in Alzheimer’s disease: study protocol for a randomised controlled trial (ELAD study). Trials,  2019, 20(1), 191.
 [http://dx.doi.org/10.1186/s13063-019-3259-x] [PMID:  30944040]

[167]
Duarte, A.I.; Candeias, E.; Alves, I.N.; Mena, D.; Silva, D.F.; Machado, N.J.; Campos, E.J.; Santos, M.S.; Oliveira, C.R.; Moreira, P.I. Liraglutide protects against brain amyloid-β1-42 accumulation in female mice with early Alzheimer’s disease-like pathology by partially rescuing oxidative/nitrosative stress and inflammation. Int. J. Mol. Sci.,  2020, 21(5), E1746.
 [http://dx.doi.org/10.3390/ijms21051746] [PMID:  32143329]

[168]
Sharma, D.; Verma, S.; Vaidya, S.; Kalia, K.; Tiwari, V. Recent updates on GLP-1 agonists: Current advancements & challenges. Biomed. Pharmacother.,  2018, 108, 952-962.
 [http://dx.doi.org/10.1016/j.biopha.2018.08.088] [PMID:  30372907]

[169]
Yaribeygi, H.; Rashidy-Pour, A.; Atkin, S.L.; Jamialahmadi, T.; Sahebkar, A. GLP-1 mimetics and cognition. Life Sci.,  2021, 264, 118645.
 [http://dx.doi.org/10.1016/j.lfs.2020.118645] [PMID:  33121988]

[170]
Lopez, O.L.; Chang, Y.; Ives, D.G.; Snitz, B.E.; Fitzpatrick, A.L.; Carlson, M.C.; Rapp, S.R.; Williamson, J.D.; Tracy, R.P.; DeKosky, S.T.; Kuller, L.H. Blood amyloid levels and risk of dementia in the Ginkgo Evaluation of Memory Study (GEMS): A longitudinal analysis. Alzheimers Dement.,  2019, 15(8), 1029-1038.
 [http://dx.doi.org/10.1016/j.jalz.2019.04.008] [PMID:  31255494]

[171]
Wan, W.; Zhang, C.; Danielsen, M.; Li, Q.; Chen, W.; Chan, Y.; Li, Y. EGb761 improves cognitive function and regulates inflammatory responses in the APP/PS1 mouse. Exp. Gerontol.,  2016, 81, 92-100.
 [http://dx.doi.org/10.1016/j.exger.2016.05.007] [PMID:  27220811]

[172]
Vellas, B.; Coley, N.; Ousset, P-J.; Berrut, G.; Dartigues, J-F.; Dubois, B.; Grandjean, H.; Pasquier, F.; Piette, F.; Robert, P.; Touchon, J.; Garnier, P.; Mathiex-Fortunet, H.; Andrieu, S. Long-term use of standardised Ginkgo biloba extract for the prevention of Alzheimer’s disease (GuidAge): a randomised placebo-controlled trial. Lancet Neurol.,  2012, 11(10), 851-859.
 [http://dx.doi.org/10.1016/S1474-4422(12)70206-5] [PMID:  22959217]

[173]
Scheltens, P.; Twisk, J.W.; Blesa, R.; Scarpini, E.; von Arnim, C.A.; Bongers, A.; Harrison, J.; Swinkels, S.H.; Stam, C.J.; de Waal, H.; Wurtman, R.J.; Wieggers, R.L.; Vellas, B.; Kamphuis, P.J. Efficacy of Souvenaid in mild Alzheimer’s disease: results from a randomized, controlled trial. J. Alzheimers Dis.,  2012, 31(1), 225-236.
 [http://dx.doi.org/10.3233/JAD-2012-121189] [PMID:  22766770]

[174]
Wallace, H.J.; Wallace, I.R.; McCaffrey, P. Cognitive decline reversed by cinacalcet. QJM,  2015, 108(1), 59-61.
 [http://dx.doi.org/10.1093/qjmed/hcs081] [PMID:  22670063]

[175]
Fischer, A.; Sananbenesi, F.; Mungenast, A.; Tsai, L.H. Targeting the correct HDAC(s) to treat cognitive disorders. Trends Pharmacol. Sci.,  2010, 31(12), 605-617.
 [http://dx.doi.org/10.1016/j.tips.2010.09.003] [PMID:  20980063]

[176]
Xuan, A.G.; Pan, X.B.; Wei, P.; Ji, W.D.; Zhang, W.J.; Liu, J.H.; Hong, L.P.; Chen, W.L.; Long, D.H. Valproic acid alleviates memory deficits and attenuates amyloid-β deposition in transgenic mouse model of Alzheimer’s disease. Mol. Neurobiol.,  2015, 51(1), 300-312.
 [http://dx.doi.org/10.1007/s12035-014-8751-4] [PMID:  24854198]

[177]
Wang, Z.; Zhang, X.J.; Li, T.; Li, J.; Tang, Y.; Le, W. Valproic acid reduces neuritic plaque formation and improves learning deficits in APP(Swe)/PS1(A246E) transgenic mice via preventing the prenatal hypoxia-induced down-regulation of neprilysin. CNS Neurosci. Ther.,  2014, 20(3), 209-217.
 [http://dx.doi.org/10.1111/cns.12186] [PMID:  24289518]

[178]
Lin, H.C.; Gean, P.W.; Wang, C.C.; Chan, Y.H.; Chen, P.S. The amygdala excitatory/inhibitory balance in a valproate-induced rat autism model. PLoS One,  2013, 8(1), e55248.
 [http://dx.doi.org/10.1371/journal.pone.0055248] [PMID:  23383124]

[179]
Silva, A.J.; Kogan, J.H.; Frankland, P.W.; Kida, S. CREB and memory. Annu. Rev. Neurosci.,  1998, 21(1), 127-148.
 [http://dx.doi.org/10.1146/annurev.neuro.21.1.127] [PMID:  9530494]

[180]
Ao, H.; Ko, S.W.; Zhuo, M. CREB activity maintains the survival of cingulate cortical pyramidal neurons in the adult mouse brain. Mol. Pain,  2006, 2, 15.
 [http://dx.doi.org/10.1186/1744-8069-2-15] [PMID:  16640787]

[181]
Valor, L.M.; Jancic, D.; Lujan, R.; Barco, A. Ultrastructural and transcriptional profiling of neuropathological misregulation of CREB function. Cell Death Differ.,  2010, 17(10), 1636-1644.
 [http://dx.doi.org/10.1038/cdd.2010.40] [PMID:  20395962]

[182]
Hong, J.G.; Kim, D.H.; Park, S.J.; Kim, J.M.; Cai, M.; Liu, X.; Lee, C.H.; Ryu, J.H. The memory-enhancing effects of Kami-ondam-tang in mice. J. Ethnopharmacol.,  2011, 137(1), 251-256.
 [http://dx.doi.org/10.1016/j.jep.2011.05.014] [PMID:  21619923]

[183]
Xu, B.; Li, X.X.; He, G.R.; Hu, J.J.; Mu, X.; Tian, S.; Du, G.H. Luteolin promotes long-term potentiation and improves cognitive functions in chronic cerebral hypoperfused rats. Eur. J. Pharmacol.,  2010, 627(1-3), 99-105.
 [http://dx.doi.org/10.1016/j.ejphar.2009.10.038] [PMID:  19857483]

[184]
Xia, M.; Huang, R.; Guo, V.; Southall, N.; Cho, M.H.; Inglese, J.; Austin, C.P.; Nirenberg, M. Identification of compounds that potentiate CREB signaling as possible enhancers of long-term memory. Proc. Natl. Acad. Sci. USA,  2009, 106(7), 2412-2417.
 [http://dx.doi.org/10.1073/pnas.0813020106] [PMID:  19196967]

[185]
Kim, D.H.; Kim, S.; Jeon, S.J.; Son, K.H.; Lee, S.; Yoon, B.H.; Cheong, J.H.; Ko, K.H.; Ryu, J.H. Tanshinone I enhances learning and memory, and ameliorates memory impairment in mice via the extracellular signal-regulated kinase signalling pathway. Br. J. Pharmacol.,  2009, 158(4), 1131-1142.
 [http://dx.doi.org/10.1111/j.1476-5381.2009.00378.x] [PMID:  19775283]

[186]
Kim, J.M.; Kim, D.H.; Park, S.J.; Park, D.H.; Jung, S.Y.; Kim, H.J.; Lee, Y.S.; Jin, C.; Ryu, J.H. The n-butanolic extract of Opuntia ficus-indica var. saboten enhances long-term memory in the passive avoidance task in mice. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2010, 34(6), 1011-1017.
 [http://dx.doi.org/10.1016/j.pnpbp.2010.05.015] [PMID:  20493231]

[187]
Trofimiuk, E.; Holownia, A.; Braszko, J.J. Activation of CREB by St. John’s wort may diminish deletorious effects of aging on spatial memory. Arch. Pharm. Res.,  2010, 33(3), 469-477.
 [http://dx.doi.org/10.1007/s12272-010-0318-y] [PMID:  20361314]

[188]
Rylatt, D.B.; Aitken, A.; Bilham, T.; Condon, G.D.; Embi, N.; Cohen, P. Glycogen synthase from rabbit skeletal muscle. Amino acid sequence at the sites phosphorylated by glycogen synthase kinase-3, and extension of the N-terminal sequence containing the site phosphorylated by phosphorylase kinase. Eur. J. Biochem.,  1980, 107(2), 529-537.
 [http://dx.doi.org/10.1111/j.1432-1033.1980.tb06060.x] [PMID:  6772446]

[189]
Kockeritz, L.; Doble, B.; Patel, S.; Woodgett, J.R. Glycogen synthase kinase-3--an overview of an over-achieving protein kinase. Curr. Drug Targets,  2006, 7(11), 1377-1388.
 [http://dx.doi.org/10.2174/1389450110607011377] [PMID:  17100578]

[190]
Frame, S.; Cohen, P. GSK3 takes centre stage more than 20 years after its discovery. Biochem. J.,  2001, 359(Pt 1), 1-16.
 [http://dx.doi.org/10.1042/bj3590001] [PMID:  11563964]

[191]
Peineau, S.; Bradley, C.; Taghibiglou, C.; Doherty, A.; Bortolotto, Z.A.; Wang, Y.T.; Collingridge, G.L. The role of GSK-3 in synaptic plasticity. Br. J. Pharmacol.,  2008, 153(S1)(Suppl. 1), S428-S437.
 [http://dx.doi.org/10.1038/bjp.2008.2] [PMID:  18311157]

[192]
Rockenstein, E.; Torrance, M.; Adame, A.; Mante, M.; Bar-on, P.; Rose, J.B.; Crews, L.; Masliah, E. Neuroprotective effects of regulators of the glycogen synthase kinase-3beta signaling pathway in a transgenic model of Alzheimer’s disease are associated with reduced amyloid precursor protein phosphorylation. J. Neurosci.,  2007, 27(8), 1981-1991.
 [http://dx.doi.org/10.1523/JNEUROSCI.4321-06.2007] [PMID:  17314294]

[193]
Toledo, E.M.; Inestrosa, N.C. Activation of Wnt signaling by lithium and rosiglitazone reduced spatial memory impairment and neurodegeneration in brains of an APPswe/PSEN1DeltaE9 mouse model of Alzheimer’s disease. Mol. Psychiatry,  2010, 15(3), 272-285, 228.
 [http://dx.doi.org/10.1038/mp.2009.72] [PMID: 19621015]

[194]
Dash, P.K.; Johnson, D.; Clark, J.; Orsi, S.A.; Zhang, M.; Zhao, J.; Grill, R.J.; Moore, A.N.; Pati, S. Involvement of the glycogen synthase kinase-3 signaling pathway in TBI pathology and neurocognitive outcome. PLoS One,  2011, 6(9), e24648.
 [http://dx.doi.org/10.1371/journal.pone.0024648] [PMID:  21935433]

[195]
Lovestone, S.; Boada, M.; Dubois, B.; Hüll, M.; Rinne, J.O.; Huppertz, H-J.; Calero, M.; Andrés, M.V.; Gómez-Carrillo, B.; León, T.; del Ser, T. A phase II trial of tideglusib in Alzheimer’s disease. J. Alzheimers Dis.,  2015, 45(1), 75-88.
 [http://dx.doi.org/10.3233/JAD-141959] [PMID:  25537011]

[196]
Zhang, X.; Yin, W.K.; Shi, X.D.; Li, Y. Curcumin activates Wnt/β-catenin signaling pathway through inhibiting the activity of GSK-3β in APPswe transfected SY5Y cells. Eur. J. Pharm. Sci.,  2011, 42(5), 540-546.
 [http://dx.doi.org/10.1016/j.ejps.2011.02.009] [PMID:  21352912]

[197]
Takai, Y.; Kishimoto, A.; Inoue, M.; Nishizuka, Y. Studies on a cyclic nucleotide-independent protein kinase and its proenzyme in mammalian tissues. I. Purification and characterization of an active enzyme from bovine cerebellum. J. Biol. Chem.,  1977, 252(21), 7603-7609.
 [http://dx.doi.org/10.1016/S0021-9258(17)41009-X] [PMID:  199593]

[198]
Hama, H.; Hara, C.; Yamaguchi, K.; Miyawaki, A. PKC signaling mediates global enhancement of excitatory synaptogenesis in neurons triggered by local contact with astrocytes. Neuron,  2004, 41(3), 405-415.
 [http://dx.doi.org/10.1016/S0896-6273(04)00007-8] [PMID:  14766179]

[199]
Brennan, A.R.; Yuan, P.; Dickstein, D.L.; Rocher, A.B.; Hof, P.R.; Manji, H.; Arnsten, A.F.T. Protein kinase C activity is associated with prefrontal cortical decline in aging. Neurobiol. Aging,  2009, 30(5), 782-792.
 [http://dx.doi.org/10.1016/j.neurobiolaging.2007.08.020] [PMID:  17919783]

[200]
Takashima, A.; Yokota, T.; Maeda, Y.; Itoh, S. Pretreatment with caerulein protects against memory impairment induced by protein kinase C inhibitors in the rat. Peptides,  1991, 12(4), 699-703.
 [http://dx.doi.org/10.1016/0196-9781(91)90122-6] [PMID:  1788133]

[201]
Conboy, L.; Foley, A.G.; O’Boyle, N.M.; Lawlor, M.; Gallagher, H.C.; Murphy, K.J.; Regan, C.M. Curcumin-induced degradation of PKC delta is associated with enhanced dentate NCAM PSA expression and spatial learning in adult and aged Wistar rats. Biochem. Pharmacol.,  2009, 77(7), 1254-1265.
 [http://dx.doi.org/10.1016/j.bcp.2008.12.011] [PMID:  19161989]

[202]
Chou, C.W.; Huang, W.J.; Tien, L.T.; Wang, S.J. (-)-Epigallocatechin gallate, the most active polyphenolic catechin in green tea, presynaptically facilitates Ca2+-dependent glutamate release via activation of protein kinase C in rat cerebral cortex. Synapse,  2007, 61(11), 889-902.
 [http://dx.doi.org/10.1002/syn.20444] [PMID:  17663453]

[203]
Alkon, D.L.; Sun, M.K.; Nelson, T.J. PKC signaling deficits: a mechanistic hypothesis for the origins of Alzheimer’s disease. Trends Pharmacol. Sci.,  2007, 28(2), 51-60.
 [http://dx.doi.org/10.1016/j.tips.2006.12.002] [PMID:  17218018]

[204]
Snow, A.D.; Cummings, J.; Lake, T.; Hu, Q.; Esposito, L.; Cam, J.; Hudson, M.; Smith, E.; Runnels, S. Exebryl-1: a novel small molecule currently in human clinical trials as a disease-modifying drug for the treatment of Alzheimer’s disease. Alzheimers Dement.,  2009, 5(4)(Suppl. 1), 418.
 [http://dx.doi.org/10.1016/j.jalz.2009.04.925]

[205]
Cherrier, M.M.; Matsumoto, A.M.; Amory, J.K.; Asthana, S.; Bremner, W.; Peskind, E.R.; Raskind, M.A.; Craft, S. Testosterone improves spatial memory in men with Alzheimer disease and mild cognitive impairment. Neurology,  2005, 64(12), 2063-2068.
 [http://dx.doi.org/10.1212/01.WNL.0000165995.98986.F1] [PMID:  15985573]

[206]
Hook, G.; Hook, V.; Kindy, M. The cysteine protease inhibitor, E64d, reduces brain amyloid-β and improves memory deficits in Alzheimer’s disease animal models by inhibiting cathepsin B, but not BACE1, β-secretase activity. J. Alzheimers Dis.,  2011, 26(2), 387-408.
 [http://dx.doi.org/10.3233/JAD-2011-110101] [PMID:  21613740]

[207]
Rakover, I.; Arbel, M.; Solomon, B. Immunotherapy against APP beta-secretase cleavage site improves cognitive function and reduces neuroinflammation in Tg2576 mice without a significant effect on brain abeta levels. Neurodegener. Dis.,  2007, 4(5), 392-402.
 [http://dx.doi.org/10.1159/000103250] [PMID:  17536186]

[208]
Honig, L.S.; Vellas, B.; Woodward, M.; Boada, M.; Bullock, R.; Borrie, M.; Hager, K.; Andreasen, N.; Scarpini, E.; Liu-Seifert, H.; Case, M.; Dean, R.A.; Hake, A.; Sundell, K.; Poole Hoffmann, V.; Carlson, C.; Khanna, R.; Mintun, M.; DeMattos, R.; Selzler, K.J.; Siemers, E. Trial of solanezumab for mild dementia due to Alzheimer’s disease. N. Engl. J. Med.,  2018, 378(4), 321-330.
 [http://dx.doi.org/10.1056/NEJMoa1705971] [PMID:  29365294]

[209]
Blennow, K.; Zetterberg, H.; Rinne, J.O.; Salloway, S.; Wei, J.; Black, R.; Grundman, M.; Liu, E.; Investigators, A. Effect of immunotherapy with bapineuzumab on cerebrospinal fluid biomarker levels in patients with mild to moderate Alzheimer disease. Arch. Neurol.,  2012, 69(8), 1002-1010.
 [http://dx.doi.org/10.1001/archneurol.2012.90] [PMID:  22473769]

[210]
Andreasen, N.; Simeoni, M.; Ostlund, H.; Lisjo, P.I.; Fladby, T.; Loercher, A.E.; Byrne, G.J.; Murray, F.; Scott-Stevens, P.T.; Wallin, A.; Zhang, Y.Y.; Bronge, L.H.; Zetterberg, H.; Nordberg, A.K.; Yeo, A.J.; Khan, S.A.; Hilpert, J.; Mistry, P.C. First administration of the Fc-attenuated anti-β amyloid antibody GSK933776 to patients with mild Alzheimer’s disease: a randomized, placebo-controlled study. PLoS One,  2015, 10(3), e0098153.
 [http://dx.doi.org/10.1371/journal.pone.0098153] [PMID:  25789616]

[211]
Landen, J.W.; Andreasen, N.; Cronenberger, C.L.; Schwartz, P.F.; Börjesson-Hanson, A.; Östlund, H.; Sattler, C.A.; Binneman, B.; Bednar, M.M. Ponezumab in mild-to-moderate Alzheimer’s disease: Randomized phase II PET-PIB study. Alzheimers Dement. (N. Y.),  2017, 3(3), 393-401.
 [http://dx.doi.org/10.1016/j.trci.2017.05.003] [PMID:  29067345]

[212]
Liu, Z.; Zhang, A.; Sun, H.; Han, Y.; Kong, L.; Wang, X. Two decades of new drug discovery and development for Alzheimer’s disease. RSC Advances,  2017, 7(10), 6046-6058.
 [http://dx.doi.org/10.1039/C6RA26737H]

[213]
Tokita, K.; Inoue, T.; Yamazaki, S.; Wang, F.; Yamaji, T.; Matsuoka, N.; Mutoh, S. FK962, a novel enhancer of somatostatin release, exerts cognitive-enhancing actions in rats. Eur. J. Pharmacol.,  2005, 527(1-3), 111-120.
 [http://dx.doi.org/10.1016/j.ejphar.2005.10.022] [PMID:  16325809]

[214]
Jucaite, A.; Öhd, J.; Potter, A.S.; Jaeger, J.; Karlsson, P.; Hannesdottir, K.; Boström, E.; Newhouse, P.A.; Paulsson, B. A randomized, double-blind, placebo-controlled crossover study of α4β 2* nicotinic acetylcholine receptor agonist AZD1446 (TC-6683) in adults with attention-deficit/hyperactivity disorder. Psychopharmacology (Berl.),  2014, 231(6), 1251-1265.
 [http://dx.doi.org/10.1007/s00213-013-3116-7] [PMID:  23640072]

[215]
Bain, E.E.; Robieson, W.; Pritchett, Y.; Garimella, T.; Abi-Saab, W.; Apostol, G.; McGough, J.J.; Saltarelli, M.D. A randomized, double-blind, placebo-controlled phase 2 study of α4β2 agonist ABT-894 in adults with ADHD. Neuropsychopharmacology,  2013, 38(3), 405-413.
 [http://dx.doi.org/10.1038/npp.2012.194] [PMID:  23032073]

[216]
Lenz, R.A.; Pritchett, Y.L.; Berry, S.M.; Llano, D.A.; Han, S.; Berry, D.A.; Sadowsky, C.H.; Abi-Saab, W.M.; Saltarelli, M.D. Adaptive, dose-finding phase 2 trial evaluating the safety and efficacy of ABT-089 in mild to moderate Alzheimer disease. Alzheimer Dis. Assoc. Disord.,  2015, 29(3), 192-199.
 [http://dx.doi.org/10.1097/WAD.0000000000000093] [PMID:  25973909]

[217]
Dunbar, G.C.; Inglis, F.; Kuchibhatla, R.; Sharma, T.; Tomlinson, M.; Wamsley, J. Effect of ispronicline, a neuronal nicotinic acetylcholine receptor partial agonist, in subjects with age associated memory impairment (AAMI). J. Psychopharmacol.,  2007, 21(2), 171-178.
 [http://dx.doi.org/10.1177/0269881107066855] [PMID:  17329297]

[218]
Shekhar, A.; Potter, W.Z.; Lightfoot, J.; Lienemann, J.; Dubé, S.; Mallinckrodt, C.; Bymaster, F.P.; McKinzie, D.L.; Felder, C.C. Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia. Am. J. Psychiatry,  2008, 165(8), 1033-1039.
 [http://dx.doi.org/10.1176/appi.ajp.2008.06091591] [PMID:  18593778]

[219]
Nathan, P.J.; Watson, J.; Lund, J.; Davies, C.H.; Peters, G.; Dodds, C.M.; Swirski, B.; Lawrence, P.; Bentley, G.D.; O’Neill, B.V.; Robertson, J.; Watson, S.; Jones, G.A.; Maruff, P.; Croft, R.J.; Laruelle, M.; Bullmore, E.T. The potent M1 receptor allosteric agonist GSK1034702 improves episodic memory in humans in the nicotine abstinence model of cognitive dysfunction. Int. J. Neuropsychopharmacol.,  2013, 16(4), 721-731.
 [http://dx.doi.org/10.1017/S1461145712000752] [PMID:  22932339]

[220]
Smith, R.C.; Amiaz, R.; Si, T.M.; Maayan, L.; Jin, H.; Boules, S.; Sershen, H.; Li, C.; Ren, J.; Liu, Y.; Youseff, M.; Lajtha, A.; Guidotti, A.; Weiser, M.; Davis, J.M. Varenicline effects on smoking, cognition, and psychiatric symptoms in schizophrenia: A double-blind randomized trial. PLoS One,  2016, 11(1), e0143490.
 [http://dx.doi.org/10.1371/journal.pone.0143490] [PMID:  26730716]

[221]
Freedman, R.; Olincy, A.; Buchanan, R.W.; Harris, J.G.; Gold, J.M.; Johnson, L.; Allensworth, D.; Guzman-Bonilla, A.; Clement, B.; Ball, M.P.; Kutnick, J.; Pender, V.; Martin, L.F.; Stevens, K.E.; Wagner, B.D.; Zerbe, G.O.; Soti, F.; Kem, W.R. Initial phase 2 trial of a nicotinic agonist in schizophrenia. Am. J. Psychiatry,  2008, 165(8), 1040-1047.
 [http://dx.doi.org/10.1176/appi.ajp.2008.07071135] [PMID:  18381905]

[222]
Keefe, R.S.; Meltzer, H.A.; Dgetluck, N.; Gawryl, M.; Koenig, G.; Moebius, H.J.; Lombardo, I.; Hilt, D.C. Randomized, double-blind, placebo-controlled study of encenicline, an α7 nicotinic acetylcholine receptor agonist, as a treatment for cognitive impairment in schizophrenia. Neuropsychopharmacology,  2015, 40(13), 3053-3060.
 [http://dx.doi.org/10.1038/npp.2015.176] [PMID:  26089183]

[223]
Arneric, S.P.; Sher, E. Current and future trends in drug discovery and development related to nicotinic receptors. In: Nicotinic Receptors; Springer, 2014; pp. 435-461.
 [http://dx.doi.org/10.1007/978-1-4939-1167-7_21]

[224]
Feuerbach, D.; Pezous, N.; Weiss, M.; Shakeri-Nejad, K.; Lingenhoehl, K.; Hoyer, D.; Hurth, K.; Bilbe, G.; Pryce, C.R.; McAllister, K.; Chaperon, F.; Kucher, K.; Johns, D.; Blaettler, T.; Lopez Lopez, C. AQW051, a novel, potent and selective α7 nicotinic ACh receptor partial agonist: pharmacological characterization and phase I evaluation. Br. J. Pharmacol.,  2015, 172(5), 1292-1304.
 [http://dx.doi.org/10.1111/bph.13001] [PMID:  25363835]

[225]
Walling, D.; Marder, S.R.; Kane, J.; Fleischhacker, W.W.; Keefe, R.S.; Hosford, D.A.; Dvergsten, C.; Segreti, A.C.; Beaver, J.S.; Toler, S.M.; Jett, J.E.; Dunbar, G.C. Phase 2 Trial of an Alpha-7 Nicotinic Receptor Agonist (TC-5619) in Negative and Cognitive Symptoms of Schizophrenia. Schizophr. Bull.,  2016, 42(2), 335-343.
 [http://dx.doi.org/10.1093/schbul/sbv072] [PMID:  26071208]

[226]
Kantrowitz, J.T.; Javitt, D.C.; Freedman, R.; Sehatpour, P.; Kegeles, L.S.; Carlson, M.; Sobeih, T.; Wall, M.M.; Choo, T.H.; Vail, B.; Grinband, J.; Lieberman, J.A. Double blind, two dose, randomized, placebo-controlled, cross-over clinical trial of the positive allosteric modulator at the alpha7 nicotinic cholinergic receptor AVL-3288 in schizophrenia patients. Neuropsychopharmacology,  2020, 45(8), 1339-1345.
 [http://dx.doi.org/10.1038/s41386-020-0628-9] [PMID:  32015461]

[227]
Schneider, L.S.; Geffen, Y.; Rabinowitz, J.; Thomas, R.G.; Schmidt, R.; Ropele, S.; Weinstock, M. Low-dose ladostigil for mild cognitive impairment: A phase 2 placebo-controlled clinical trial. Neurology,  2019, 93(15), e1474-e1484.
 [http://dx.doi.org/10.1212/WNL.0000000000008239] [PMID:  31492718]

[228]
Hampel, H.; Williams, C.; Etcheto, A.; Goodsaid, F.; Parmentier, F.; Sallantin, J.; Kaufmann, W.E.; Missling, C.U.; Afshar, M. A precision medicine framework using artificial intelligence for the identification and confirmation of genomic biomarkers of response to an Alzheimer’s disease therapy: Analysis of the blarcamesine (ANAVEX2-73) Phase 2a clinical study. Alzheimers Dement. (N. Y.),  2020, 6(1), e12013.
 [http://dx.doi.org/10.1002/trc2.12013] [PMID:  32318621]

[229]
Goff, D.C.; Lamberti, J.S.; Leon, A.C.; Green, M.F.; Miller, A.L.; Patel, J.; Manschreck, T.; Freudenreich, O.; Johnson, S.A. A placebo-controlled add-on trial of the Ampakine, CX516, for cognitive deficits in schizophrenia. Neuropsychopharmacology,  2008, 33(3), 465-472.
 [http://dx.doi.org/10.1038/sj.npp.1301444] [PMID:  17487227]

[230]
Bernard, K.; Danober, L.; Thomas, J.Y.; Lebrun, C.; Muñoz, C.; Cordi, A.; Desos, P.; Lestage, P.; Morain, P. DRUG FOCUS: S 18986: A positive allosteric modulator of AMPA-type glutamate receptors pharmacological profile of a novel cognitive enhancer. CNS Neurosci. Ther.,  2010, 16(5), e193-e212.
 [http://dx.doi.org/10.1111/j.1755-5949.2009.00088.x] [PMID:  21050420]

[231]
Preskorn, S.; Macaluso, M.; Mehra, D.O.; Zammit, G.; Moskal, J.R.; Burch, R.M. Randomized proof of concept trial of GLYX-13, an N-methyl-D-aspartate receptor glycine site partial agonist, in major depressive disorder nonresponsive to a previous antidepressant agent. J. Psychiatr. Pract.,  2015, 21(2), 140-149.
 [http://dx.doi.org/10.1097/01.pra.0000462606.17725.93] [PMID:  25782764]

[232]
Berry-Kravis, E.; Hessl, D.; Coffey, S.; Hervey, C.; Schneider, A.; Yuhas, J.; Hutchison, J.; Snape, M.; Tranfaglia, M.; Nguyen, D.V.; Hagerman, R. A pilot open label, single dose trial of fenobam in adults with fragile X syndrome. J. Med. Genet.,  2009, 46(4), 266-271.
 [http://dx.doi.org/10.1136/jmg.2008.063701] [PMID:  19126569]

[233]
Berry-Kravis, E.; Des Portes, V.; Hagerman, R.; Jacquemont, S.; Charles, P.; Visootsak, J.; Brinkman, M.; Rerat, K.; Koumaras, B.; Zhu, L.; Barth, G.M.; Jaecklin, T.; Apostol, G.; von Raison, F. Mavoglurant in fragile X syndrome: Results of two randomized, double-blind, placebo-controlled trials. Sci. Transl. Med.,  2016, 8(321), 321ra5.
 [http://dx.doi.org/10.1126/scitranslmed.aab4109] [PMID:  26764156]

[234]
Kent, J.M.; Daly, E.; Kezic, I.; Lane, R.; Lim, P.; De Smedt, H.; De Boer, P.; Van Nueten, L.; Drevets, W.C.; Ceusters, M. Efficacy and safety of an adjunctive mGlu2 receptor positive allosteric modulator to a SSRI/SNRI in anxious depression. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2016, 67, 66-73.
 [http://dx.doi.org/10.1016/j.pnpbp.2016.01.009] [PMID:  26804646]

[235]
Litman, R.E.; Smith, M.A.; Doherty, J.J.; Cross, A.; Raines, S.; Gertsik, L.; Zukin, S.R. AZD8529, a positive allosteric modulator at the mGluR2 receptor, does not improve symptoms in schizophrenia: A proof of principle study. Schizophr. Res.,  2016, 172(1-3), 152-157.
 [http://dx.doi.org/10.1016/j.schres.2016.02.001] [PMID:  26922656]

[236]
Schoemaker, J.H.; Jansen, W.T.; Schipper, J.; Szegedi, A. The selective glycine uptake inhibitor org 25935 as an adjunctive treatment to atypical antipsychotics in predominant persistent negative symptoms of schizophrenia: results from the GIANT trial. J. Clin. Psychopharmacol.,  2014, 34(2), 190-198.
 [http://dx.doi.org/10.1097/JCP.0000000000000073] [PMID:  24525661]

[237]
Kraus, M.S.; Gold, J.M.; Barch, D.M.; Walker, T.M.; Chun, C.A.; Buchanan, R.W.; Csernansky, J.G.; Goff, D.C.; Green, M.F.; Jarskog, L.F.; Javitt, D.C.; Kimhy, D.; Lieberman, J.A.; McEvoy, J.P.; Mesholam-Gately, R.I.; Seidman, L.J.; Ball, M.P.; Kern, R.S.; McMahon, R.P.; Robinson, J.; Marder, S.R.; Keefe, R.S.E. The characteristics of cognitive neuroscience tests in a schizophrenia cognition clinical trial: Psychometric properties and correlations with standard measures. Schizophr. Res. Cogn.,  2019, 19, 100161.
 [http://dx.doi.org/10.1016/j.scog.2019.100161] [PMID:  31832342]

[238]
Buchanan, R.W.; Keefe, R.S.; Lieberman, J.A.; Barch, D.M.; Csernansky, J.G.; Goff, D.C.; Gold, J.M.; Green, M.F.; Jarskog, L.F.; Javitt, D.C.; Kimhy, D.; Kraus, M.S.; McEvoy, J.P.; Mesholam-Gately, R.I.; Seidman, L.J.; Ball, M.P.; McMahon, R.P.; Kern, R.S.; Robinson, J.; Marder, S.R. A randomized clinical trial of MK-0777 for the treatment of cognitive impairments in people with schizophrenia. Biol. Psychiatry,  2011, 69(5), 442-449.
 [http://dx.doi.org/10.1016/j.biopsych.2010.09.052] [PMID:  21145041]

[239]
Atack, J.R. Subtype-selective GABA(A) receptor modulation yields a novel pharmacological profile: the design and development of TPA023. Adv. Pharmacol.,  2009, 57, 137-185.
 [http://dx.doi.org/10.1016/S1054-3589(08)57004-9] [PMID:  20230761]

[240]
Potier, M-C.; Reeves, R.H. Intellectual disabilities in Down syndrome from birth and throughout life: Assessment and treatment. Front. Behav. Neurosci.,  2016, 10, 120.
 [http://dx.doi.org/10.3389/fnbeh.2016.00120] [PMID:  27378871]

[241]
Hatayama, Y.; Hashimoto, T.; Kohayakawa, H.; Kiyoshi, T.; Nakamichi, K.; Kinoshita, T.; Yoshida, N. In vivo pharmacological characterization of AC-3933, a benzodiazepine receptor partial inverse agonist for the treatment of Alzheimer’s disease. Neuroscience,  2014, 265, 217-225.
 [http://dx.doi.org/10.1016/j.neuroscience.2014.01.063] [PMID:  24513386]

[242]
Manzano, S.; Agüera, L.; Aguilar, M.; Olazarán, J. A review on tramiprosate (homotaurine) in Alzheimer’s disease and other neurocognitive disorders. Front. Neurol.,  2020, 11, 614.
 [http://dx.doi.org/10.3389/fneur.2020.00614] [PMID:  32733362]

[243]
DeMartinis, N., III; Lopez, R.N.; Pickering, E.H.; Schmidt, C.J.; Gertsik, L.; Walling, D.P.; Ogden, A. A proof-of-concept study evaluating the phosphodiesterase 10A inhibitor PF-02545920 in the adjunctive treatment of suboptimally controlled symptoms of schizophrenia. J. Clin. Psychopharmacol.,  2019, 39(4), 318-328.
 [http://dx.doi.org/10.1097/JCP.0000000000001047] [PMID:  31205187]

[244]
Walling, D.P.; Banerjee, A.; Dawra, V.; Boyer, S.; Schmidt, C.J.; DeMartinis, N. Phosphodiesterase 10A inhibitor monotherapy is not an effective treatment of acute schizophrenia. J. Clin. Psychopharmacol.,  2019, 39(6), 575-582.
 [http://dx.doi.org/10.1097/JCP.0000000000001128] [PMID:  31688451]

[245]
Prickaerts, J.; Heckman, P.R.A.; Blokland, A. Investigational phosphodiesterase inhibitors in phase I and phase II clinical trials for Alzheimer’s disease. Expert Opin. Investig. Drugs,  2017, 26(9), 1033-1048.
 [http://dx.doi.org/10.1080/13543784.2017.1364360] [PMID:  28772081]

[246]
Lee, J.Y.; Lee, H.; Yoo, H.B.; Choi, J.S.; Jung, H.Y.; Yoon, E.J.; Kim, H.; Jung, Y.H.; Lee, H.Y.; Kim, Y.K. Efficacy of cilostazol administration in Alzheimer’s disease patients with white matter lesions: a positron-emission tomography study. Neurotherapeutics,  2019, 16(2), 394-403.
 [http://dx.doi.org/10.1007/s13311-018-00708-x] [PMID:  30761509]

[247]
Maher-Edwards, G.; Zvartau-Hind, M.; Hunter, A.J.; Gold, M.; Hopton, G.; Jacobs, G.; Davy, M.; Williams, P. Double-blind, controlled phase II study of a 5-HT6 receptor antagonist, SB-742457, in Alzheimer’s disease. Curr. Alzheimer Res.,  2010, 7(5), 374-385.
 [http://dx.doi.org/10.2174/156720510791383831] [PMID:  20043816]

[248]
Atri, A.; Frölich, L.; Ballard, C.; Tariot, P.N.; Molinuevo, J.L.; Boneva, N.; Windfeld, K.; Raket, L.L.; Cummings, J.L. 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.
 [http://dx.doi.org/10.1001/jama.2017.20373] [PMID:  29318278]

[249]
Li, H.; Luo, J.; Wang, C.; Xie, S.; Xu, X.; Wang, X.; Yu, W.; Gu, N.; Kane, J.M. Efficacy and safety of aripiprazole in Chinese Han schizophrenia subjects: a randomized, double-blind, active parallel-controlled, multicenter clinical trial. Schizophr. Res.,  2014, 157(1-3), 112-119.
 [http://dx.doi.org/10.1016/j.schres.2014.05.040] [PMID:  24994555]

[250]
Schoenberg, M.R.; Rum, R.S.; Osborn, K.E.; Werz, M.A. A randomized, double-blind, placebo-controlled crossover study of the effects of levetiracetam on cognition, mood, and balance in healthy older adults. Epilepsia,  2017, 58(9), 1566-1574.
 [http://dx.doi.org/10.1111/epi.13849] [PMID:  28731266]

[251]
Weintraub, D.; Hauser, R.A.; Elm, J.J.; Pagan, F.; Davis, M.D.; Choudhry, A.; Investigators, M. Rasagiline for mild cognitive impairment in Parkinson’s disease: A placebo-controlled trial. Mov. Disord.,  2016, 31(5), 709-714.
 [http://dx.doi.org/10.1002/mds.26617] [PMID:  27030249]

[252]
Follow-up evaluation of cognitive function in the randomized Alzheimer’s disease anti-inflammatory prevention trial and its follow-up study. Alzheimers Dement.,  2015, 11(2), 216-25.e1.
 [http://dx.doi.org/10.1016/j.jalz.2014.03.009] [PMID:  25022541]

[253]
Bakota, L.; Brandt, R. Tau biology and tau-directed therapies for Alzheimer’s disease. Drugs,  2016, 76(3), 301-313.
 [http://dx.doi.org/10.1007/s40265-015-0529-0] [PMID:  26729186]

[254]
Rosell, D.R.; Zaluda, L.C.; McClure, M.M.; Perez-Rodriguez, M.M.; Strike, K.S.; Barch, D.M.; Harvey, P.D.; Girgis, R.R.; Hazlett, E.A.; Mailman, R.B.; Abi-Dargham, A.; Lieberman, J.A.; Siever, L.J. Effects of the D1 dopamine receptor agonist dihydrexidine (DAR-0100A) on working memory in schizotypal personality disorder. Neuropsychopharmacology,  2015, 40(2), 446-453.
 [http://dx.doi.org/10.1038/npp.2014.192] [PMID:  25074637]

[255]
Butchart, J.; Brook, L.; Hopkins, V.; Teeling, J.; Püntener, U.; Culliford, D.; Sharples, R.; Sharif, S.; McFarlane, B.; Raybould, R.; Thomas, R.; Passmore, P.; Perry, V.H.; Holmes, C. Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trial. Neurology,  2015, 84(21), 2161-2168.
 [http://dx.doi.org/10.1212/WNL.0000000000001617] [PMID:  25934853]

[256]
Suzuki, H.; Gen, K. Clinical efficacy of lamotrigine and changes in the dosages of concomitantly used psychotropic drugs in Alzheimer’s disease with behavioural and psychological symptoms of dementia: a preliminary open-label trial. Psychogeriatrics,  2015, 15(1), 32-37.
 [http://dx.doi.org/10.1111/psyg.12085] [PMID:  25516380]

[257]
Gauthier, S.; Rountree, S.; Finn, B.; LaPlante, B.; Weber, E.; Oltersdorf, T. 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.
 [http://dx.doi.org/10.3233/JAD-150414] [PMID:  26402011]

[258]
Lin, Y.; Wang, K.; Ma, C.; Wang, X.; Gong, Z.; Zhang, R.; Zang, D.; Cheng, Y. Evaluation of metformin on cognitive improvement in patients with non-dementia vascular cognitive impairment and abnormal glucose metabolism. Front. Aging Neurosci.,  2018, 10, 227.
 [http://dx.doi.org/10.3389/fnagi.2018.00227] [PMID:  30100873]

[259]
Perna, S.; Mainardi, M.; Astrone, P.; Gozzer, C.; Biava, A.; Bacchio, R.; Spadaccini, D.; Solerte, S.B.; Rondanelli, M. 12-month effects of incretins versus SGLT2-Inhibitors on cognitive performance and metabolic profile. A randomized clinical trial in the elderly with Type-2 diabetes mellitus. Clin. Pharmacol.,  2018, 10, 141-151.
 [http://dx.doi.org/10.2147/CPAA.S164785] [PMID:  30349407]

[260]
Mansur, R.B.; Ahmed, J.; Cha, D.S.; Woldeyohannes, H.O.; Subramaniapillai, M.; Lovshin, J.; Lee, J.G.; Lee, J-H.; Brietzke, E.; Reininghaus, E.Z.; Sim, K.; Vinberg, M.; Rasgon, N.; Hajek, T.; McIntyre, R.S. Liraglutide promotes improvements in objective measures of cognitive dysfunction in individuals with mood disorders: A pilot, open-label study. J. Affect. Disord.,  2017, 207, 114-120.
 [http://dx.doi.org/10.1016/j.jad.2016.09.056] [PMID:  27721184]

[261]
Demarin, V. Bašić Kes, V.; Trkanjec, Z.; Budišić M.; Bošnjak Pašić M.; Črnac, P.; Budinčević H. Efficacy and safety of Ginkgo biloba standardized extract in the treatment of vascular cognitive impairment: a randomized, double-blind, placebo-controlled clinical trial. Neuropsychiatr. Dis. Treat.,  2017, 13, 483-490.
 [http://dx.doi.org/10.2147/NDT.S120790] [PMID:  28243101]

[262]
Henderson, V.W.; Ala, T.; Sainani, K.L.; Bernstein, A.L.; Stephenson, B.S.; Rosen, A.C.; Farlow, M.R. Raloxifene for women with Alzheimer disease: A randomized controlled pilot trial. Neurol.,  2015, 85(22), 1937-1944.
 [http://dx.doi.org/10.1212/WNL.0000000000002171] [PMID:  26537053]

[263]
Scheltens, P.; Hallikainen, M.; Grimmer, T.; Duning, T.; Gouw, A.A.; Teunissen, C.E.; Wink, A.M.; Maruff, P.; Harrison, J.; van Baal, C.M.; Bruins, S.; Lues, I.; Prins, N.D. Safety, tolerability and efficacy of the glutaminyl cyclase inhibitor PQ912 in Alzheimer’s disease: results of a randomized, double-blind, placebo-controlled phase 2a study. Alzheimers Res. Ther.,  2018, 10(1), 107.
 [http://dx.doi.org/10.1186/s13195-018-0431-6] [PMID:  30309389]
Rights & Permissions Print Cite
Article Metrics
3
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1570159X20666220411083922	Print ISSN 1570-159X
Publisher Name Bentham Science Publisher	Online ISSN 1875-6190
Current Neuropharmacology

Strategies for Treatment of Disease-Associated Dementia Beyond Alzheimer's Disease: An Update

Abstract Play Pause

Graphical Abstract

Related Journals

Related Books

Abstract
