{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:40:01Z","timestamp":1792014001688,"version":"4.4.0"},"reference-count":150,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T00:00:00Z","timestamp":1689292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1A2A3074577"],"award-info":[{"award-number":["2018R1A2A3074577"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1A5A2031612"],"award-info":[{"award-number":["2021R1A5A2031612"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022S1A5C2A03092407"],"award-info":[{"award-number":["2022S1A5C2A03092407"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Education","award":["2018R1A2A3074577"],"award-info":[{"award-number":["2018R1A2A3074577"]}]},{"name":"Ministry of Education","award":["2021R1A5A2031612"],"award-info":[{"award-number":["2021R1A5A2031612"]}]},{"name":"Ministry of Education","award":["2022S1A5C2A03092407"],"award-info":[{"award-number":["2022S1A5C2A03092407"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Insulin resistance as a hallmark of type 2 DM (T2DM) plays a role in dementia by promoting pathological lesions or enhancing the vulnerability of the brain. Numerous studies related to insulin\/insulin-like growth factor 1 (IGF-1) signaling are linked with various types of dementia. Brain insulin resistance in dementia is linked to disturbances in A\u03b2 production and clearance, Tau hyperphosphorylation, microglial activation causing increased neuroinflammation, and the breakdown of tight junctions in the blood\u2013brain barrier (BBB). These mechanisms have been studied primarily in Alzheimer\u2019s disease (AD), but research on other forms of dementia like vascular dementia (VaD), Lewy body dementia (LBD), and frontotemporal dementia (FTD) has also explored overlapping mechanisms. Researchers are currently trying to repurpose anti-diabetic drugs to treat dementia, which are dominated by insulin sensitizers and insulin substrates. Although it seems promising and feasible, none of the trials have succeeded in ameliorating cognitive decline in late-onset dementia. We highlight the possibility of repositioning anti-diabetic drugs as a strategy for dementia therapy by reflecting on current and previous clinical trials. We also describe the molecular perspectives of various types of dementia through the insulin\/IGF-1 signaling pathway.<\/jats:p>","DOI":"10.3390\/ijms241411450","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T08:35:47Z","timestamp":1689323747000},"page":"11450","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Repositioning of Anti-Diabetic Drugs against Dementia: Insight from Molecular Perspectives to Clinical Trials"],"prefix":"10.3390","volume":"24","author":[{"given":"Keren Esther Kristina","family":"Mantik","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Research Center for Controlling Intercellular Communication, College of Medicine, Inha University, Incheon 22212, Republic of Korea"},{"name":"Program in Biomedical Science and Engineering, Inha University, Incheon 22212, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Research Center for Controlling Intercellular Communication, College of Medicine, Inha University, Incheon 22212, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonsang","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Research Center for Controlling Intercellular Communication, College of Medicine, Inha University, Incheon 22212, Republic of Korea"},{"name":"Program in Biomedical Science and Engineering, Inha University, Incheon 22212, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohee","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Research Center for Controlling Intercellular Communication, College of Medicine, Inha University, Incheon 22212, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0451-4554","authenticated-orcid":false,"given":"Hyo-Bum","family":"Kwak","sequence":"additional","affiliation":[{"name":"Program in Biomedical Science and Engineering, Inha University, Incheon 22212, Republic of Korea"},{"name":"Department of Kinesiology, College of Arts and Sports, Inha University, Incheon 22212, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1863-0652","authenticated-orcid":false,"given":"Dong-Ho","family":"Park","sequence":"additional","affiliation":[{"name":"Program in Biomedical Science and Engineering, Inha University, Incheon 22212, Republic of Korea"},{"name":"Department of Kinesiology, College of Arts and Sports, Inha University, Incheon 22212, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5235-8993","authenticated-orcid":false,"given":"Ju-Hee","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Research Center for Controlling Intercellular Communication, College of Medicine, Inha University, Incheon 22212, Republic of Korea"},{"name":"Program in Biomedical Science and Engineering, Inha University, Incheon 22212, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,14]]},"reference":[{"key":"ref_1","first-page":"833","article-title":"Drug Repositioning for Alzheimer\u2019s Disease","volume":"11","author":"Corbett","year":"2012","journal-title":"Nat. Publ. Group"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101234","DOI":"10.1016\/j.molmet.2021.101234","article-title":"The Brain as an Insulin-Sensitive Metabolic Organ","volume":"52","author":"Milstein","year":"2021","journal-title":"Mol. Metab."},{"key":"ref_3","unstructured":"Gauthier, S., Rosa-Neto, P., Morais, J.A., and Webster, C. (2021). World Alzheimer Report 2021: Journey Through the Diagnosis of Dementia, Alzheimer\u2019s Disease International."},{"key":"ref_4","unstructured":"International Diabetes Federation (2021). IDF Diabetes Atlas, International Diabetes Federation. [10th ed.]."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/S1474-4422(14)70136-X","article-title":"Potential for Primary Prevention of Alzheimer\u2019s Disease: An Analysis of Population-Based Data","volume":"13","author":"Norton","year":"2014","journal-title":"Lancet Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1007\/s00127-018-1581-3","article-title":"Mild Cognitive Impairment and Progression to Dementia in People with Diabetes, Prediabetes and Metabolic Syndrome: A Systematic Review and Meta-Analysis","volume":"53","author":"Pal","year":"2018","journal-title":"Soc. Psychiatr. Epidemiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1056\/NEJMp2110468","article-title":"Revisiting FDA Approval of Aducanumab","volume":"385","author":"Alexander","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/nature19323","article-title":"The Antibody Aducanumab Reduces A\u03b2 Plaques in Alzheimer\u2019s Disease","volume":"537","author":"Sevigny","year":"2016","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1001\/jama.2022.24494","article-title":"Lecanemab Gains FDA Approval for Early Alzheimer Disease","volume":"329","author":"Larkin","year":"2023","journal-title":"JAMA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in Early Alzheimer\u2019s Disease","volume":"388","author":"Swanson","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s12929-017-0355-7","article-title":"Drug Candidates in Clinical Trials for Alzheimer\u2019s Disease","volume":"24","author":"Hung","year":"2017","journal-title":"J. Biomed. Sci."},{"key":"ref_12","first-page":"25","article-title":"Buntanetap, a Novel Translational Inhibitor of Multiple Neurotoxic Proteins, Proves to Be Safe and Promising in Both Alzheimer\u2019s and Parkinson\u2019s Patients","volume":"10","author":"Fang","year":"2023","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1152\/ajpcell.00240.2017","article-title":"Insulin Transport into the Brain","volume":"315","author":"Gray","year":"2018","journal-title":"Am. J. Physiol. Cell. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.ejphar.2004.02.040","article-title":"The Source of Cerebral Insulin","volume":"490","author":"Banks","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/j.neuron.2010.08.007","article-title":"Neuronal Activity Drives Localized Blood-Brain-Barrier Transport of Serum Insulin-like Growth Factor-I into the CNS","volume":"67","author":"Nishijima","year":"2010","journal-title":"Neuron"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ejphar.2004.02.042","article-title":"Signaling by Insulin-like Growth Factor 1 in Brain","volume":"490","author":"Bondy","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/jnr.490340206","article-title":"Insulin-like Growth Factor-I (IGF-I) Production by Astroglial Cells: Regulation and Importance for Epidermal Growth Factor-Induced Cell Replication","volume":"34","author":"Chernausek","year":"1993","journal-title":"J. Neurosci. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1002\/jnr.20288","article-title":"Astrocyte-Specific Overexpression of Insulin-like Growth Factor-I Promotes Brain Overgrowth and Glial Fibrillary Acidic Protein Expression","volume":"78","author":"Ye","year":"2004","journal-title":"J. Neurosci. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"365","DOI":"10.3389\/fnagi.2017.00365","article-title":"Insulin-like Growth Factor-1 and Neuroinflammation","volume":"9","author":"Labandeira","year":"2017","journal-title":"Front. Aging. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0169-409X(98)00088-X","article-title":"The Blood-Brain Barrier Efflux Transporters as a Detoxifying System for the Brain","volume":"36","author":"Terasaki","year":"1999","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1007\/s00125-016-3996-2","article-title":"Cerebral Cortex: A Target and Source of Insulin?","volume":"59","year":"2016","journal-title":"Diabetologia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0167-0115(93)90335-6","article-title":"Insulin II Gene Expression in Rat Central Nervous System","volume":"48","author":"Devaskar","year":"1993","journal-title":"Regul. Pept."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8445","DOI":"10.1016\/S0021-9258(17)37214-9","article-title":"Insulin Gene Expression and Insulin Synthesis in Mammalian Neuronal Cells","volume":"269","author":"Devaskar","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"289","DOI":"10.3233\/JAD-190921","article-title":"Patients with Alzheimer\u2019s Disease Have Increased Levels of Insulin-like Growth Factor-I in Serum but Not in Cerebrospinal Fluid","volume":"75","author":"Horvath","year":"2020","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.pneurobio.2013.06.004","article-title":"Decoding Alzheimer\u2019s Disease from Perturbed Cerebral Glucose Metabolism: Implications for Diagnostic and Therapeutic Strategies","volume":"108","author":"Chen","year":"2013","journal-title":"Prog. Neurobiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5851","DOI":"10.1523\/JNEUROSCI.5180-14.2015","article-title":"Neuronal LRP1 Regulates Glucose Metabolism and Insulin Signaling in the Brain","volume":"35","author":"Liu","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.molmet.2018.01.013","article-title":"Insulin-like Growth Factor Receptor Signaling Regulates Working Memory, Mitochondrial Metabolism, and Amyloid-\u03b2 Uptake in Astrocytes","volume":"9","author":"Logan","year":"2018","journal-title":"Mol. Metab."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Brabazon, F., Bermudez, S., Shaughness, M., Khayrullina, G., and Byrnes, K.R. (2018). The Effects of Insulin on the Inflammatory Activity of BV2 Microglia. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0201878"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"684","DOI":"10.2174\/1567205012666150710104428","article-title":"Insulin Modulates In Vitro Secretion of Cytokines and Cytotoxins by Human Glial Cells","volume":"12","author":"Spielman","year":"2015","journal-title":"Curr. Alzheimer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1186\/1742-2094-10-37","article-title":"Insulin-like Growth Factor 1 and 2 (IGF1, IGF2) Expression in Human Microglia: Differential Regulation by Inflammatory Mediators","volume":"10","author":"Suh","year":"2013","journal-title":"J. Neuroinflamm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1111\/jnc.12267","article-title":"Insulin-like Growth Factor-1 Abrogates Microglial Oxidative Stress and TNF-\u03b1 Responses to Spreading Depression","volume":"126","author":"Grinberg","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zheng, W.H., and Quirion, R. (2006). Insulin-like Growth Factor-1 (IGF-1) Induces the Activation\/Phosphorylation of Akt Kinase and CAMP Response Element-Binding Protein (CREB) by Activating Different Signaling Pathways in PC12 Cells. BMC Neurosci., 7.","DOI":"10.1186\/1471-2202-7-51"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1002\/jcp.24607","article-title":"IGF-1 Alleviates NMDA-Induced Excitotoxicity in Cultured Hippocampal Neurons Against Autophagy via the NR2B\/PI3K-AKT-MTOR Pathway","volume":"229","author":"Wang","year":"2014","journal-title":"J. Cell. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1523\/JNEUROSCI.18-06-02118.1998","article-title":"Insulin-Like Growth Factor-I Is a Differentiation Factor for Postmitotic CNS Stem Cell-Derived Neuronal Precursors: Distinct Actions from Those of Brain-Derived Neurotrophic Factor","volume":"18","author":"Arsenijevic","year":"1998","journal-title":"J. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"28","DOI":"10.3389\/fneur.2011.00028","article-title":"Exercise-Induced Cognitive Plasticity, Implications for Mild Cognitive Impairment and Alzheimer\u2019s Disease","volume":"2","author":"Foster","year":"2011","journal-title":"Front. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3389\/fnana.2018.00035","article-title":"A Putative Mechanism of Age-Related Synaptic Dysfunction Based on the Impact of IGF-1 Receptor Signaling on Synaptic CaMKII\u03b1 Phosphorylation","volume":"12","author":"Ogundele","year":"2018","journal-title":"Front. Neuroanat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3927","DOI":"10.2337\/db15-0596","article-title":"Hippocampal Insulin Resistance Impairs Spatial Learning and Synaptic Plasticity","volume":"64","author":"Grillo","year":"2015","journal-title":"Diabetes"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1096\/fasebj.14.7.1015","article-title":"Insulin Regulates Soluble Amyloid Precursor Protein Release via Phosphatidyl Inositol 3 Kinase-dependent Pathway","volume":"14","author":"Solano","year":"2000","journal-title":"FASEB J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1152\/physrev.1997.77.4.1081","article-title":"Cellular Actions of Amyloid Precursor Protein and Its Soluble and Fibrillogenic Derivatives","volume":"77","author":"Mattson","year":"1997","journal-title":"Physiol. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1101\/lm.88005","article-title":"Insulin Receptor Signaling in Long-Term Memory Consolidation Following Spatial Learning","volume":"12","author":"Dou","year":"2005","journal-title":"Learn. Mem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/nrn3209","article-title":"The Many Faces of Insulin-like Peptide Signalling in the Brain","volume":"13","author":"Fernandez","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1172\/JCI59903","article-title":"Demonstrated Brain Insulin Resistance in Alzheimer\u2019s Disease Patients Is Associated with IGF-1 Resistance, IRS-1 Dysregulation, and Cognitive Decline","volume":"122","author":"Talbot","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.bbi.2018.03.032","article-title":"Inflammation, Insulin Signaling and Cognitive Function in Aged APP\/PS1 Mice","volume":"70","author":"Denver","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.bbr.2017.11.015","article-title":"Diabetes Mellitus and Alzheimer\u2019s Disease: GSK-3\u03b2 as a Potential Link","volume":"339","author":"Zhang","year":"2018","journal-title":"Behav. Brain Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"srep46359","DOI":"10.1038\/srep46359","article-title":"Insulin Deprivation Induces PP2A Inhibition and Tau Hyperphosphorylation in HTau Mice, a Model of Alzheimer\u2019s Disease-like Tau Pathology","volume":"7","author":"Gratuze","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.3233\/JAD-150926","article-title":"Brain-Specific Basal and Novelty-Induced Alternations in PI3K-Akt and MAPK\/ERK Signaling in a Middle-Aged A\u03b2PP\/PS1 Mouse Model of Alzheimer\u2019s Disease","volume":"51","author":"Guillot","year":"2016","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.neuropharm.2017.09.016","article-title":"Reduced Brain Insulin Signaling: A Seminal Process in Alzheimer\u2019s Disease Pathogenesis","volume":"136","author":"Bloom","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1007\/s12035-019-01858-5","article-title":"Alzheimer\u2019s Disease and Diabetes: Insulin Signaling as the Bridge Linking Two Pathologies","volume":"57","author":"Shieh","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.2337\/db11-1735","article-title":"Altered APP Processing in Insulin-Resistant Conditions Is Mediated by Autophagosome Accumulation via the Inhibition of Mammalian Target of Rapamycin Pathway","volume":"61","author":"Son","year":"2012","journal-title":"Diabetes"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/1750-1326-5-46","article-title":"Insulin Deficiency Exacerbates Cerebral Amyloidosis and Behavioral Deficits in an Alzheimer Transgenic Mouse Model","volume":"5","author":"Wang","year":"2010","journal-title":"Mol. Neurodegener."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1523\/JNEUROSCI.22-10-j0001.2002","article-title":"Alzheimer\u2019s Beta-Amyloid Peptides Compete for Insulin Binding to the Insulin Receptor","volume":"22","author":"Xie","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.tem.2015.11.003","article-title":"Targeting Insulin-Degrading Enzyme to Treat Type 2 Diabetes Mellitus","volume":"27","author":"Tang","year":"2016","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1002\/path.5777","article-title":"Insulin-Degrading Enzyme: An Ally against Metabolic and Neurodegenerative Diseases","volume":"255","author":"Sousa","year":"2021","journal-title":"J. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"610","DOI":"10.2174\/1567205015666180119105446","article-title":"Characteristics of Insulin-Degrading Enzyme in Alzheimer\u2019s Disease: A Meta-Analysis","volume":"15","author":"Zhang","year":"2018","journal-title":"Curr. Alzheimer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3389\/fncel.2019.00017","article-title":"The Link between Tau and Insulin Signaling: Implications for Alzheimer\u2019s Disease and Other Tauopathies","volume":"13","author":"Wijesekara","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"249","DOI":"10.3233\/JAD-150035","article-title":"Activation of the 5\u2032-AMP-Activated Protein Kinase in the Cerebral Cortex of Young Senescence-Accelerated P8 Mice and Association with GSK3\u03b2- and PP2A-Dependent Inhibition of p-Tau396 Expression","volume":"46","author":"Kim","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Sayas, C.L., and \u00c1vila, J. (2021). GSK-3 and Tau: A Key Duet in Alzheimer\u2019s Disease. Cells, 10.","DOI":"10.3390\/cells10040721"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1038\/mp.2016.214","article-title":"Caspase-3-Dependent Cleavage of Akt Modulates Tau Phosphorylation via GSK3\u03b2 Kinase: Implications for Alzheimer\u2019s Disease","volume":"22","author":"Chu","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_59","first-page":"2277","article-title":"To Be or Not to Be: PP2A as a Dual Player in CNS Functions, Its Role in Neurodegeneration, and Its Interaction with Brain Insulin Signaling","volume":"76","author":"Javadpour","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3389\/fnmol.2014.00016","article-title":"Protein Phosphatase 2A Dysfunction in Alzheimer\u2019s Disease","volume":"7","author":"Sontag","year":"2014","journal-title":"Front. Mol. Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"13","DOI":"10.4236\/aad.2017.61002","article-title":"Role of GSK3\u03b2 and PP2A on Regulation of Tau Phosphorylation in Hippocampus and Memory Impairment in ICV-STZ Animal Model of Alzheimer\u2019s Disease","volume":"6","author":"Hong","year":"2017","journal-title":"Adv. Alzheimer Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"17913","DOI":"10.1073\/pnas.0804610105","article-title":"T Lymphocytes Potentiate Endogenous Neuroprotective Inflammation in a Mouse Model of ALS","volume":"105","author":"Chiu","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.cmet.2019.06.005","article-title":"A Breakdown in Metabolic Reprogramming Causes Microglia Dysfunction in Alzheimer\u2019s Disease","volume":"30","author":"Baik","year":"2019","journal-title":"Cell. Metab."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/s41583-022-00558-9","article-title":"Impaired Insulin Signalling and Allostatic Load in Alzheimer Disease","volume":"23","author":"Ferreira","year":"2022","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.pneurobio.2016.01.001","article-title":"Astrogliosis: An Integral Player in the Pathogenesis of Alzheimer\u2019s Disease","volume":"144","author":"Osborn","year":"2016","journal-title":"Prog. Neurobiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"629","DOI":"10.3389\/fnins.2019.00629","article-title":"Altered Insulin Signaling in Alzheimer\u2019s Disease Brain-Special Emphasis on Pi3k-Akt Pathway","volume":"13","author":"Gabbouj","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.cell.2017.07.023","article-title":"TREM2 Maintains Microglial Metabolic Fitness in Alzheimer\u2019s Disease","volume":"170","author":"Ulland","year":"2017","journal-title":"Cell"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nrneurol.2017.188","article-title":"Blood-Brain Barrier Breakdown in Alzheimer Disease and Other Neurodegenerative Disorders","volume":"14","author":"Sweeney","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"521","DOI":"10.3389\/fnins.2019.00521","article-title":"Role of the Blood-Brain Barrier in Central Nervous System Insulin Resistance","volume":"13","author":"Rhea","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"112933","DOI":"10.1016\/j.biopha.2022.112933","article-title":"HMGB1 Signaling Pathway in Diabetes-Related Dementia: Blood-Brain Barrier Breakdown, Brain Insulin Resistance, and A\u03b2 Accumulation","volume":"150","author":"Jeong","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1161\/01.STR.0000083050.44441.10","article-title":"Operational Definitions for the NINDS-AIREN Criteria for Vascular Dementia an Interobserver Study","volume":"34","author":"Scheltens","year":"2003","journal-title":"Stroke"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1016\/S0140-6736(15)00463-8","article-title":"Vascular Dementia","volume":"386","author":"Thomas","year":"2015","journal-title":"Lancet"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.mce.2012.12.016","article-title":"Hyperglycemia Is Associated with Enhanced Gluconeogenesis in a Rat Model of Permanent Cerebral Ischemia","volume":"367","author":"Wang","year":"2013","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.jphs.2019.01.013","article-title":"Ginsenoside Compound K Attenuates Cognitive Deficits in Vascular Dementia Rats by Reducing the A\u03b2 Deposition","volume":"139","author":"Zong","year":"2019","journal-title":"J. Pharmacol. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.neulet.2012.01.077","article-title":"Down-Regulation of IGF-1\/IGF-1R in Hippocampus of Rats with Vascular Dementia","volume":"513","author":"Gong","year":"2012","journal-title":"Neurosci. Lett."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s40478-021-01176-9","article-title":"Brain Insulin Signaling and Cerebrovascular Disease in Human Postmortem Brain","volume":"9","author":"Arvanitakis","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.psyneuen.2017.09.018","article-title":"Low Serum Insulin-like Growth Factor-I (IGF-I) Level Is Associated with Increased Risk of Vascular Dementia","volume":"86","author":"Quinlan","year":"2017","journal-title":"Psychoneuroendocrinology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"585","DOI":"10.3233\/JAD-2009-0995","article-title":"Brain Insulin-like Growth Factor and Neurotrophin Resistance in Parkinson\u2019s Disease and Dementia with Lewy Bodies: Potential Role of Manganese Neurotoxicity","volume":"16","author":"Tong","year":"2009","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1159\/000371510","article-title":"Plasma Insulin-like Growth Factor 1 Is Associated with Cognitive Impairment in Parkinson\u2019s Disease","volume":"39","author":"Ma","year":"2015","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1002\/ana.25811","article-title":"Evolution of Alzheimer\u2019s Disease Cerebrospinal Fluid Biomarkers in Early Parkinson\u2019s Disease","volume":"88","author":"Irwin","year":"2020","journal-title":"Ann. Neurol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1007\/s00401-016-1552-2","article-title":"CSF Biomarkers Associated with Disease Heterogeneity in Early Parkinson\u2019s Disease: The Parkinson\u2019s Progression Markers Initiative Study","volume":"131","author":"Kang","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_82","unstructured":"Deleon, J., and Miller, B.L. (2018). Handbook of Clinical Neurology, Elsevier B.V.. [1st ed.]."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1759091419839515","article-title":"Altered Brain Expression of Insulin and Insulin-Like Growth Factors in Frontotemporal Lobar Degeneration: Another Degenerative Disease Linked to Dysregulation of Insulin Metabolic Pathways","volume":"11","author":"Liou","year":"2019","journal-title":"ASN Neuro."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1212\/WNL.0000000000000993","article-title":"Systemic Metabolism in Frontotemporal Dementia","volume":"83","author":"Ahmed","year":"2014","journal-title":"Neurology"},{"key":"ref_85","first-page":"e17219","article-title":"A Comprehensive Review of Intranasal Insulin and Its Effect on the Cognitive Function of Diabetics","volume":"13","author":"Gaddam","year":"2021","journal-title":"Cureus"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"715","DOI":"10.3233\/JAD-150307","article-title":"Central Nervous System Delivery of Intranasal Insulin: Mechanisms of Uptake and Effects on Cognition","volume":"47","author":"Salameh","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1111\/acel.12498","article-title":"Intranasal Insulin Alleviates Cognitive Deficits and Amyloid Pathology in Young Adult APPswe\/PS1dE9 Mice","volume":"15","author":"Mao","year":"2016","journal-title":"Aging Cell"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"111812","DOI":"10.1016\/j.exger.2022.111812","article-title":"MicroRNA Modulation Is a Potential Molecular Mechanism for Neuroprotective Effects of Intranasal Insulin Administration in Amyloid \u0392eta Oligomer Induced Alzheimer\u2019s like Rat Model","volume":"164","author":"Bazrgar","year":"2022","journal-title":"Exp. Gerontol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"329","DOI":"10.3233\/JAD-2012-121294","article-title":"Intranasal Insulin Ameliorates Tau Hyperphosphorylation in a Rat Model of Type 2 Diabetes","volume":"33","author":"Yang","year":"2013","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.expneurol.2014.06.004","article-title":"Intranasal Insulin Restores Insulin Signaling, Increases Synaptic Proteins, and Reduces A\u03b2 Level and Microglia Activation in the Brains of 3xTg-AD Mice","volume":"261","author":"Chen","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"srep45971","DOI":"10.1038\/srep45971","article-title":"Long-Term Treatment with Intranasal Insulin Ameliorates Cognitive Impairment, Tau Hyperphosphorylation, and Microglial Activation in a Streptozotocin-Induced Alzheimer\u2019s Rat Model","volume":"7","author":"Guo","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1007\/s12640-017-9809-7","article-title":"Intranasal Insulin Ameliorates Cerebral Hypometabolism, Neuronal Loss, and Astrogliosis in Streptozotocin-Induced Alzheimer\u2019s Rat Model","volume":"33","author":"Chen","year":"2018","journal-title":"Neurotox. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"120299","DOI":"10.1016\/j.lfs.2021.120299","article-title":"Mechanistic Insight into the Role of Metformin in Alzheimer\u2019s Disease","volume":"291","author":"Sanati","year":"2022","journal-title":"Life Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"120538","DOI":"10.1016\/j.lfs.2022.120538","article-title":"Intranasal Metformin Treatment Ameliorates Cognitive Functions via Insulin Signaling Pathway in ICV-STZ-Induced Mice Model of Alzheimer\u2019s Disease","volume":"299","author":"Kazkayasi","year":"2022","journal-title":"Life Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.pbb.2012.03.002","article-title":"Metformin Attenuates Alzheimer\u2019s Disease-like Neuropathology in Obese, Leptin-Resistant Mice","volume":"101","author":"Li","year":"2012","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1371\/journal.pone.0102420","article-title":"The Anti-Diabetic Drug Metformin Reduces BACE1 Protein Level by Interfering with the MID1 Complex","volume":"9","author":"Hettich","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3907","DOI":"10.1073\/pnas.0807991106","article-title":"Antidiabetic Drug Metformin (GlucophageR) Increases Biogenesis of Alzheimer\u2019s Amyloid Peptides via up-Regulating BACE1 Transcription","volume":"106","author":"Chen","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"136136","DOI":"10.1016\/j.neulet.2021.136136","article-title":"Metformin Attenuates Vascular Pathology by Increasing Expression of Insulin-Degrading Enzyme in a Mixed Model of Cerebral Amyloid Angiopathy and Type 2 Diabetes Mellitus","volume":"762","author":"Inoue","year":"2021","journal-title":"Neurosci. Lett."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1111\/j.1532-5415.2012.03916.x","article-title":"Metformin, Other Antidiabetic Drugs, and Risk of Alzheimer\u2019s Disease: A Population-Based Case-Control Study","volume":"60","author":"Imfeld","year":"2012","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.3233\/JAD-220180","article-title":"Association Between Metformin and Alzheimer\u2019s Disease: A Systematic Review and Meta-Analysis of Clinical Observational Studies","volume":"88","author":"Luo","year":"2022","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e001370","DOI":"10.1136\/bmjdrc-2020-001370","article-title":"Association between Metformin and Neurodegenerative Diseases of Observational Studies: Systematic Review and Meta-Analysis","volume":"8","author":"Ping","year":"2020","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"ref_102","unstructured":"Cardoso, S., and Moreira, P.I. (2020). International Review of Neurobiology, Elsevier Inc.. [1st ed.]."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"178","DOI":"10.3389\/fnagi.2019.00178","article-title":"Pioglitazone Reduces \u03b2 Amyloid Levels via Inhibition of PPAR\u03b3 Phosphorylation in a Neuronal Model of Alzheimer\u2019s Disease","volume":"10","author":"Quan","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1038\/npp.2010.32","article-title":"Rosiglitazone Rescues Memory Impairment in Alzheimer\u2019s Transgenic Mice: Mechanisms Involving a Reduced Amyloid and Tau Pathology","volume":"35","author":"Escribano","year":"2010","journal-title":"Neuropsychopharmacology"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1097\/MAJ.0000000000000499","article-title":"Rosiglitazone Improves Learning and Memory Ability in Rats with Type 2 Diabetes Through the Insulin Signaling Pathway","volume":"350","author":"Ma","year":"2015","journal-title":"Am. J. Med. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1017\/S1461145711001611","article-title":"The Effect of Rosiglitazone on LRP1 Expression and Amyloid \u03b2 Uptake in Human Brain Microvascular Endothelial Cells: A Possible Role of a Low-Dose Thiazolidinedione for Dementia Treatment","volume":"15","author":"Moon","year":"2012","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.pbb.2011.08.020","article-title":"Behavioral and Biochemical Investigations to Explore Pharmacological Potential of PPAR-Gamma Agonists in Vascular Dementia of Diabetic Rats","volume":"100","author":"Sharma","year":"2011","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/1753-0407.13352","article-title":"Thiazolidinedione Use Is Associated with Reduced Risk of Dementia in Patients with Type 2 Diabetes Mellitus: A Retrospective Cohort Study","volume":"15","author":"Zhao","year":"2023","journal-title":"J. Diabetes"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1002\/alz.12474","article-title":"Brain Energy Failure in Dementia Syndromes: Opportunities and Challenges for Glucagon-like Peptide-1 Receptor Agonists","volume":"18","author":"Yassine","year":"2022","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1002\/jnr.24706","article-title":"Insulin Deficiency, but Not Resistance, Exaggerates Cognitive Deficits in Transgenic Mice Expressing Human Amyloid and Tau Proteins. Reversal by Exendin-4 Treatment","volume":"98","author":"King","year":"2020","journal-title":"J. Neurosci. Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"741923","DOI":"10.3389\/fnagi.2021.741923","article-title":"Liraglutide Reduces Vascular Damage, Neuronal Loss, and Cognitive Impairment in a Mixed Murine Model of Alzheimer\u2019s Disease and Type 2 Diabetes","volume":"13","author":"Herrera","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1007\/s12031-019-1257-9","article-title":"Combination of Insulin with a GLP1 Agonist Is Associated with Better Memory and Normal Expression of Insulin Receptor Pathway Genes in a Mouse Model of Alzheimer\u2019s Disease","volume":"67","author":"Robinson","year":"2019","journal-title":"J. Mol. Neurosci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.neuropharm.2013.08.005","article-title":"Liraglutide Can Reverse Memory Impairment, Synaptic Loss and Reduce Plaque Load in Aged APP\/PS1 Mice, a Model of Alzheimer\u2019s Disease","volume":"76","author":"McClean","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/path.5056","article-title":"The Diabetes Drug Liraglutide Reverses Cognitive Impairment in Mice and Attenuates Insulin Receptor and Synaptic Pathology in a Non-Human Primate Model of Alzheimer\u2019s Disease","volume":"245","author":"Batista","year":"2018","journal-title":"J. Pathol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e12268","DOI":"10.1002\/trc2.12268","article-title":"Treatment with Glucagon-like Peptide-1 Receptor Agonists and Incidence of Dementia: Data from Pooled Double-Blind Randomized Controlled Trials and Nationwide Disease and Prescription Registers","volume":"8","author":"Friedrich","year":"2022","journal-title":"Alzheimer\u2019s Dement. Transl. Res. Clin. Interv."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"173416","DOI":"10.1016\/j.ejphar.2020.173416","article-title":"Glibenclamide Modulates Microglial Function and Attenuates A\u03b2 Deposition in 5XFAD Mice","volume":"884","author":"Ju","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"112359","DOI":"10.1016\/j.bbr.2019.112359","article-title":"Glibenclamide Mitigates Cognitive Impairment and Hippocampal Neuroinflammation in Rats with Type 2 Diabetes and Sporadic Alzheimer-like Disease","volume":"379","author":"Esmaeili","year":"2020","journal-title":"Behav. Brain Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.brainresbull.2018.01.001","article-title":"ATP-Sensitive Potassium-Channel Inhibitor Glibenclamide Attenuates HPA Axis Hyperactivity, Depression- and Anxiety-Related Symptoms in a Rat Model of Alzheimer\u2019s Disease","volume":"137","author":"Esmaeili","year":"2018","journal-title":"Brain Res. Bull."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e003036","DOI":"10.1136\/bmjdrc-2022-003036","article-title":"Comparative Effect of Metformin versus Sulfonylureas with Dementia and Parkinson\u2019s Disease Risk in US Patients over 50 with Type 2 Diabetes Mellitus","volume":"10","author":"Newby","year":"2022","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1007\/s00213-023-06341-7","article-title":"Molecular and Neural Roles of Sodium-Glucose Cotransporter 2 Inhibitors in Alleviating Neurocognitive Impairment in Diabetic Mice","volume":"240","author":"Herbet","year":"2023","journal-title":"Psychopharmacology"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/14791641221098168","article-title":"The Association between Sodium-Glucose Cotransporter 2 Inhibitors and Incident Dementia: A Nationwide Population-Based Longitudinal Cohort Study","volume":"19","author":"Siao","year":"2022","journal-title":"Diab. Vasc. Dis. Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1007\/s10787-022-00973-5","article-title":"Dapagliflozin as an Autophagic Enhancer via LKB1\/AMPK\/SIRT1 Pathway in Ovariectomized\/d-Galactose Alzheimer\u2019s Rat Model","volume":"30","author":"Ibrahim","year":"2022","journal-title":"Inflammopharmacology"},{"key":"ref_123","first-page":"1894","article-title":"Amylin Pharmacology in Alzheimer\u2019s Disease Pathogenesis and Treatment","volume":"20","author":"Corrigan","year":"2021","journal-title":"Curr. Neuropharmacol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.molmed.2017.06.003","article-title":"Amylin Receptor: A Potential Therapeutic Target for Alzheimer\u2019s Disease","volume":"23","author":"Fu","year":"2017","journal-title":"Trends Mol. Med."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.neurobiolaging.2013.10.076","article-title":"Neuroprotective Effects of the Amylin Analogue Pramlintide on Alzheimer\u2019s Disease Pathogenesis and Cognition","volume":"35","author":"Adler","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1080\/13813455.2018.1534244","article-title":"Effect of Amylin on Memory and Central Insulin Resistance in a Rat Model of Alzheimer\u2019s Disease","volume":"126","author":"Nassar","year":"2020","journal-title":"Arch. Physiol. Biochem."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.neuropharm.2017.12.016","article-title":"Amylin in Alzheimer\u2019s Disease: Pathological Peptide or Potential Treatment?","volume":"136","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"154265","DOI":"10.1016\/j.metabol.2020.154265","article-title":"Impact of Antidiabetic Agents on Dementia Risk: A Bayesian Network Meta-Analysis","volume":"109","author":"Zhou","year":"2020","journal-title":"Metabolism"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/sj.npp.1301193","article-title":"Intranasal Insulin Improves Memory in Humans: Superiority of Insulin Aspart","volume":"32","author":"Benedict","year":"2007","journal-title":"Neuropsychopharmacology"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1016\/j.psyneuen.2004.04.003","article-title":"Intranasal Insulin Improves Memory in Humans","volume":"29","author":"Benedict","year":"2004","journal-title":"Psychoneuroendocrinology"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1001\/archneurol.2011.233","article-title":"Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial","volume":"69","author":"Craft","year":"2012","journal-title":"Arch. Neurol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"789","DOI":"10.3233\/JAD-122308","article-title":"Sex and ApoE Genotype Differences in Treatment Response to Two Doses of Intranasal Insulin in Adults with Mild Cognitive Impairment or Alzheimer\u2019s Disease","volume":"35","author":"Claxton","year":"2013","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"897","DOI":"10.3233\/JAD-141791","article-title":"Long-Acting Intranasal Insulin Detemir Improves Cognition for Adults with Mild Cognitive Impairment or Early-Stage Alzheimer\u2019s Disease Dementia","volume":"44","author":"Claxton","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.3233\/JAD-161256","article-title":"Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer\u2019s Disease Biomarkers: A Pilot Clinical Trial","volume":"57","author":"Craft","year":"2017","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1001\/jamaneurol.2020.1840","article-title":"Safety, Efficacy, and Feasibility of Intranasal Insulin for the Treatment of Mild Cognitive Impairment and Alzheimer Disease Dementia: A Randomized Clinical Trial","volume":"77","author":"Craft","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1097\/WAD.0000000000000202","article-title":"Effects of the Insulin Sensitizer Metformin in Alzheimer Disease","volume":"31","author":"Koenig","year":"2017","journal-title":"Alzheimer Dis. Assoc. Disord."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"501","DOI":"10.3233\/JAD-150493","article-title":"Metformin in Amnestic Mild Cognitive Impairment: Results of a Pilot Randomized Placebo Controlled Clinical Trial","volume":"51","author":"Luchsinger","year":"2016","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_138","first-page":"1177","article-title":"Long Term Treatment with Metformin in Patients with Type 2 Diabetes and Risk of Vitamin B-12 Deficiency: Randomised Placebo Controlled Trial","volume":"340","author":"Kooy","year":"2010","journal-title":"BMJ"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1210\/jc.2015-3754","article-title":"Long-Term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study","volume":"101","author":"Aroda","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1007\/s00415-019-09363-4","article-title":"An Update on Genetic Frontotemporal Dementia","volume":"266","author":"Greaves","year":"2019","journal-title":"J. Neurol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S1474-4422(21)00043-0","article-title":"Safety and Efficacy of Pioglitazone for the Delay of Cognitive Impairment in People at Risk of Alzheimer\u2019s Disease (TOMMORROW): A Prognostic Biomarker Study and a Phase 3, Randomised, Double-Blind, Placebo-Controlled Trial","volume":"20","author":"Burns","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1159\/000371509","article-title":"Effects of Pioglitazone or Exercise in Older Adults with Mild Cognitive Impairment and Insulin Resistance: A Pilot Study","volume":"5","author":"Hildreth","year":"2015","journal-title":"Dement. Geriatr. Cogn. Dis. Extra"},{"key":"ref_143","first-page":"950","article-title":"Preserved Cognition in Patients With Early Alzheimer Disease and Amnestic Mild Cognitive Impairment During Treatment With Rosiglitazone","volume":"13","author":"Watson","year":"2005","journal-title":"Am. J. Geriatr. Psychiatry"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"592","DOI":"10.2174\/156720511796391935","article-title":"Rosiglitazone Does Not Improve Cognition or Global Function When Used as Adjunctive Therapy to AChE Inhibitors in Mild-to-Moderate Alzheimers Disease: Two Phase 3 Studies","volume":"8","author":"Harrington","year":"2011","journal-title":"Curr. Alzheimer Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1159\/000318845","article-title":"Rosiglitazone Monotherapy in Mild-to-Moderate Alzheimer\u2019s Disease: Results from a Randomized, Double-Blind, Placebo-Controlled Phase III Study","volume":"30","author":"Gold","year":"2010","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3389\/fnagi.2016.00108","article-title":"In Alzheimer\u2019s Disease, 6-Month Treatment with GLP-1 Analog Prevents Decline of Brain Glucose Metabolism: Randomized, Placebo-Controlled, Double-Blind Clinical Trial","volume":"8","author":"Gejl","year":"2016","journal-title":"Front. Aging Neurosci."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1186\/s13063-019-3259-x","article-title":"Evaluating the Effects of the Novel GLP-1 Analogue Liraglutide in Alzheimer\u2019s Disease: Study Protocol for a Randomised Controlled Trial (ELAD Study)","volume":"20","author":"Femminella","year":"2019","journal-title":"Trials"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"741","DOI":"10.2174\/1567205016666190913155950","article-title":"A Pilot Study of Exenatide Actions in Alzheimer\u2019s Disease","volume":"16","author":"Mullins","year":"2019","journal-title":"Curr. Alzheimer Res."},{"key":"ref_149","first-page":"403","article-title":"Longitudinal Cerebrospinal Fluid Biomarker Measurements in Preclinical Sporadic Alzheimer\u2019s Disease: A Prospective 9-Year Study","volume":"1","author":"Stomrud","year":"2015","journal-title":"Alzheimer\u2019s Dement. Diagn. Assess. Dis. 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