Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links
At present, Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are two highly prevalent disorders worldwide, especially among elderly individuals. T2DM appears to be associated with cognitive dysfunction, with a higher risk of developing neurocognitive disorders, including AD. These diseas...
- Autores:
-
Rojas, Milagros
Chávez-Castillo, Mervin
Ba, Jordan
Ortega, Ángel
Nava, Manuel
Salazar, Juan
Díaz-Camargo, Edgar
Rojas-Quintero, Joselyn
Bermúdez, Valmore
- Tipo de recurso:
- Fecha de publicación:
- 2021
- Institución:
- Universidad Simón Bolívar
- Repositorio:
- Repositorio Digital USB
- Idioma:
- eng
- OAI Identifier:
- oai:bonga.unisimon.edu.co:20.500.12442/8410
- Acceso en línea:
- https://hdl.handle.net/20.500.12442/8410
http://dx.doi.org/10.4239/wjd.v12.i6.745
https://www.wjgnet.com/1948-9358/full/v12/i6/745.htm
- Palabra clave:
- Alzheimer’s disease
Type 2 diabetes mellitus
Oxidative stress
Islet amyloid polypeptide
Glucagon-like peptide 1
Cognitive dysfunction
Hypoglycemic agents
- Rights
- openAccess
- License
- Attribution-NonCommercial-NoDerivatives 4.0 Internacional
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Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links |
| title |
Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links |
| spellingShingle |
Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links Alzheimer’s disease Type 2 diabetes mellitus Oxidative stress Islet amyloid polypeptide Glucagon-like peptide 1 Cognitive dysfunction Hypoglycemic agents |
| title_short |
Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links |
| title_full |
Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links |
| title_fullStr |
Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links |
| title_full_unstemmed |
Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links |
| title_sort |
Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links |
| dc.creator.fl_str_mv |
Rojas, Milagros Chávez-Castillo, Mervin Ba, Jordan Ortega, Ángel Nava, Manuel Salazar, Juan Díaz-Camargo, Edgar Rojas-Quintero, Joselyn Bermúdez, Valmore |
| dc.contributor.author.none.fl_str_mv |
Rojas, Milagros Chávez-Castillo, Mervin Ba, Jordan Ortega, Ángel Nava, Manuel Salazar, Juan Díaz-Camargo, Edgar Rojas-Quintero, Joselyn Bermúdez, Valmore |
| dc.subject.eng.fl_str_mv |
Alzheimer’s disease Type 2 diabetes mellitus Oxidative stress Islet amyloid polypeptide Glucagon-like peptide 1 Cognitive dysfunction Hypoglycemic agents |
| topic |
Alzheimer’s disease Type 2 diabetes mellitus Oxidative stress Islet amyloid polypeptide Glucagon-like peptide 1 Cognitive dysfunction Hypoglycemic agents |
| description |
At present, Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are two highly prevalent disorders worldwide, especially among elderly individuals. T2DM appears to be associated with cognitive dysfunction, with a higher risk of developing neurocognitive disorders, including AD. These diseases have been observed to share various pathophysiological mechanisms, including alterations in insulin signaling, defects in glucose transporters (GLUTs), and mitochondrial dysfunctions in the brain. Therefore, the aim of this review is to summarize the current knowledge regarding the molecular mechanisms implicated in the association of these pathologies as well as recent therapeutic alternatives. In this context, the hyperphosphorylation of tau and the formation of neurofibrillary tangles have been associated with the dysfunction of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways in the nervous tissues as well as the decrease in the expression of GLUT-1 and GLUT-3 in the different areas of the brain, increase in reactive oxygen species, and production of mitochondrial alterations that occur in T2DM. These findings have contributed to the implementation of overlapping pharmacological interventions based on the use of insulin and antidiabetic drugs, or, more recently, azeliragon, amylin, among others, which have shown possible beneficial effects in diabetic patients diagnosed with AD. |
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2021 |
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2021-09-17T16:49:56Z |
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2021-09-17T16:49:56Z |
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2021 |
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Artículo científico |
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Rojas M, Chávez-Castillo M, Bautista J, Ortega Á, Nava M, Salazar J, Díaz-Camargo E, Medina O, Rojas-Quintero J, Bermúdez V. Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links. World J Diabetes 2021; 12(6): 745-766 |
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19489358 |
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https://hdl.handle.net/20.500.12442/8410 |
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http://dx.doi.org/10.4239/wjd.v12.i6.745 |
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https://www.wjgnet.com/1948-9358/full/v12/i6/745.htm |
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Rojas M, Chávez-Castillo M, Bautista J, Ortega Á, Nava M, Salazar J, Díaz-Camargo E, Medina O, Rojas-Quintero J, Bermúdez V. Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links. World J Diabetes 2021; 12(6): 745-766 19489358 |
| url |
https://hdl.handle.net/20.500.12442/8410 http://dx.doi.org/10.4239/wjd.v12.i6.745 https://www.wjgnet.com/1948-9358/full/v12/i6/745.htm |
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eng |
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eng |
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Attribution-NonCommercial-NoDerivatives 4.0 Internacional |
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pdf |
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Baishideng Publishing Group Inc |
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World Journal of Diabetes |
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Rojas, Milagrosd07a9d4d-cce2-438c-b4a0-fc5ed4af1a67Chávez-Castillo, Mervin912e1d3d-18fb-43af-8edb-826137f74a5aBa, Jordan03e0da9a-c765-4242-99cc-c9599355d347Ortega, Ángelb6a809bb-4d26-4e53-9419-e4eb9fb40a9bNava, Manuelcf0ca570-5fc3-4ec7-9913-90be952261e2Salazar, Juanfbd053e7-5aea-424c-812f-92153ecb9181Díaz-Camargo, Edgare056554f-7c70-4102-b9c6-bad4ba6afb39Rojas-Quintero, Joselyn1fcd6ac1-186e-465c-a5fd-3c25563275abBermúdez, Valmore29f9aa18-16a4-4fd3-8ce5-ed94a0b8663a2021-09-17T16:49:56Z2021-09-17T16:49:56Z2021Rojas M, Chávez-Castillo M, Bautista J, Ortega Á, Nava M, Salazar J, Díaz-Camargo E, Medina O, Rojas-Quintero J, Bermúdez V. Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links. World J Diabetes 2021; 12(6): 745-76619489358https://hdl.handle.net/20.500.12442/8410http://dx.doi.org/10.4239/wjd.v12.i6.745https://www.wjgnet.com/1948-9358/full/v12/i6/745.htmAt present, Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are two highly prevalent disorders worldwide, especially among elderly individuals. T2DM appears to be associated with cognitive dysfunction, with a higher risk of developing neurocognitive disorders, including AD. These diseases have been observed to share various pathophysiological mechanisms, including alterations in insulin signaling, defects in glucose transporters (GLUTs), and mitochondrial dysfunctions in the brain. Therefore, the aim of this review is to summarize the current knowledge regarding the molecular mechanisms implicated in the association of these pathologies as well as recent therapeutic alternatives. In this context, the hyperphosphorylation of tau and the formation of neurofibrillary tangles have been associated with the dysfunction of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways in the nervous tissues as well as the decrease in the expression of GLUT-1 and GLUT-3 in the different areas of the brain, increase in reactive oxygen species, and production of mitochondrial alterations that occur in T2DM. These findings have contributed to the implementation of overlapping pharmacological interventions based on the use of insulin and antidiabetic drugs, or, more recently, azeliragon, amylin, among others, which have shown possible beneficial effects in diabetic patients diagnosed with AD.pdfengBaishideng Publishing Group IncAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2World Journal of DiabetesVol. 12, No.6 (2021)Alzheimer’s diseaseType 2 diabetes mellitusOxidative stressIslet amyloid polypeptideGlucagon-like peptide 1Cognitive dysfunctionHypoglycemic agentsAlzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics linksinfo:eu-repo/semantics/articleArtículo científicohttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_2df8fbb1World Health Organization. Dementia. [cited 21 October 2020]. In: World Health Organization [Internet]. Available from: https://www.who.int/news-room/fact-sheets/detail/dementiaAmerican Diabetes Association. 12. Older Adults: Standards of Medical Care in Diabetes-2020. Diabetes Care 2020; 43: S152-S162 [PMID: 31862755 DOI: 10.2337/dc20-S012]International Diabetes Federation. Worldwide toll of diabetes. [cited 21 October 2020]. In: International Diabetes Federation [Internet]. Available from: https://diabetesatlas.org/en/sections/worldwide-toll-of-diabetes.htmInternational Diabetes Federation. Worldwide toll of diabetes. [cited 21 October 2020]. In: International Diabetes Federation [Internet]. Available from: https://diabetesatlas.org/en/sections/worldwide-toll-of-diabetes.htmAlicic RZ, Rooney MT, Tuttle KR. Diabetic Kidney Disease: Challenges, Progress, and Possibilities. Clin J Am Soc Nephrol 2017; 12: 2032-2045 [PMID: 28522654 DOI: 10.2215/CJN.11491116]Yau JW, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, Chen SJ, Dekker JM, Fletcher A, Grauslund J, Haffner S, Hamman RF, Ikram MK, Kayama T, Klein BE, Klein R, Krishnaiah S, Mayurasakorn K, O'Hare JP, Orchard TJ, Porta M, Rema M, Roy MS, Sharma T, Shaw J, Taylor H, Tielsch JM, Varma R, Wang JJ, Wang N, West S, Xu L, Yasuda M, Zhang X, Mitchell P, Wong TY; Meta-Analysis for Eye Disease (META-EYE) Study Group. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 2012; 35: 556-564 [PMID: 22301125 DOI: 10.2337/dc11-1909]Mirhoseini M, Saleh N, Momeni A, Deris F, Asadi-Samani M. A study on the association of diabetic dermopathy with nephropathy and retinopathy in patients with type 2 diabetes mellitus. J Nephropathol 2016; 5: 139-143 [PMID: 27921026 DOI: 10.15171/jnp.2016.26]Thiruvoipati T, Kielhorn CE, Armstrong EJ. Peripheral artery disease in patients with diabetes: Epidemiology, mechanisms, and outcomes. World J Diabetes 2015; 6: 961-969 [PMID: 26185603 DOI: 10.4239/wjd.v6.i7.961]Xue M, Xu W, Ou YN, Cao XP, Tan MS, Tan L, Yu JT. Diabetes mellitus and risks of cognitive impairment and dementia: A systematic review and meta-analysis of 144 prospective studies. Ageing Res Rev 2019; 55: 100944 [PMID: 31430566 DOI: 10.1016/j.arr.2019.100944]Dá Mesquita S, Ferreira AC, Sousa JC, Correia-Neves M, Sousa N, Marques F. Insights on the pathophysiology of Alzheimer's disease: The crosstalk between amyloid pathology, neuroinflammation and the peripheral immune system. Neurosci Biobehav Rev 2016; 68: 547-562 [PMID: 27328788 DOI: 10.1016/j.neubiorev.2016.06.014]Sandhir R, Gupta S. Molecular and biochemical trajectories from diabetes to Alzheimer's disease: A critical appraisal. World J Diabetes 2015; 6: 1223-1242 [PMID: 26464760 DOI: 10.4239/wjd.v6.i12.1223]Samuel VT, Shulman GI. The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux. J Clin Invest 2016; 126: 12-22 [PMID: 26727229 DOI: 10.1172/JCI77812]Craft S, Claxton A, Baker LD, Hanson AJ, Cholerton B, Trittschuh EH, Dahl D, Caulder E, Neth B, Montine TJ, Jung Y, Maldjian J, Whitlow C, Friedman S. Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer's Disease Biomarkers: A Pilot Clinical Trial. J Alzheimers Dis 2017; 57: 1325-1334 [PMID: 28372335 DOI: 10.3233/JAD-161256]Koepsell H. Glucose transporters in brain in health and disease. Pflugers Arch 2020; 472: 1299-1343 [PMID: 32789766 DOI: 10.1007/s00424-020-02441-xMergenthaler P, Lindauer U, Dienel GA, Meisel A. Sugar for the brain: the role of glucose in physiological and pathological brain function. Trends Neurosci 2013; 36: 587-597 [PMID: 23968694 DOI: 10.1016/j.tins.2013.07.001]McAllister MS, Krizanac-Bengez L, Macchia F, Naftalin RJ, Pedley KC, Mayberg MR, Marroni M, Leaman S, Stanness KA, Janigro D. Mechanisms of glucose transport at the blood-brain barrier: an in vitro study. Brain Res 2001; 904: 20-30 [PMID: 11516408 DOI: 10.1016/s0006-8993(01)02418-0]Jurcovicova J. Glucose transport in brain - effect of inflammation. Endocr Regul 2014; 48: 35-48 [PMID: 24524374 DOI: 10.4149/endo_2014_01_35]Qutub AA, Hunt CA. Glucose transport to the brain: a systems model. Brain Res Brain Res Rev 2005; 49: 595-617 [PMID: 16269321 DOI: 10.1016/j.brainresrev.2005.03.002]Bedse G, Di Domenico F, Serviddio G, Cassano T. Aberrant insulin signaling in Alzheimer's disease: current knowledge. Front Neurosci 2015; 9: 204 [PMID: 26136647 DOI: 10.3389/fnins.2015.00204]Blázquez E, Velázquez E, Hurtado-Carneiro V, Ruiz-Albusac JM. Insulin in the brain: its pathophysiological implications for States related with central insulin resistance, type 2 diabetes and Alzheimer's disease. Front Endocrinol (Lausanne) 2014; 5: 161 [PMID: 25346723 DOI: 10.3389/fendo.2014.00161]Rojas J, Bermúdez V, Leal E, Cano R, Luti Y, Acosta L, Finol F, AparicioD, Arraiz N, Linares S, Rojas E, Canelón R, Deisiree S. Insulinorresistencia e hiperinsulinemia como factores de riesgo para enfermedad cardiovascular. Arch Venez Farmacol Ter 2008; 27: 30-40Baranowska-Bik A, Bik W. Insulin and brain aging. Prz Menopauzalny 2017; 16: 44-46 [PMID: 28721128 DOI: 10.5114/pm.2017.68590]Tascone LDS, Bottino CMC. Neurobiology of neuropsychiatric symptoms in Alzheimer's disease: A critical review with a focus on neuroimaging. Dement Neuropsychol 2013; 7: 236-243 [PMID: 29213845 DOI: 10.1590/S1980-57642013DN70300002]Narvaez E, Pelaez J, Almeida K, Alvarez C, Mendoza C, Morales A, Godos D, Del Salto Ocaña T, Catota M. Implication of apolipoprotein e polymorphisms in the atherosclerosis and Alzheimer’s disease physiopathology. Rev Latinoam Hipertens 2018; 13: 97-102Gilbert BJ. The role of amyloid β in the pathogenesis of Alzheimer's disease. J Clin Pathol 2013; 66: 362-366 [PMID: 23526599 DOI: 10.1136/jclinpath-2013-201515]Yu JT, Tan L, Hardy J. Apolipoprotein E in Alzheimer's disease: an update. Annu Rev Neurosci 2014; 37: 79-100 [PMID: 24821312 DOI: 10.1146/annurev-neuro-071013-014300]Sadigh-Eteghad S, Sabermarouf B, Majdi A, Talebi M, Farhoudi M, Mahmoudi J. Amyloid-beta: a crucial factor in Alzheimer's disease. Med Princ Pract 2015; 24: 1-10 [PMID: 25471398 DOI: 10.1159/000369101]Varma VR, Varma S, An Y, Hohman TJ, Seddighi S, Casanova R, Beri A, Dammer EB, Seyfried NT, Pletnikova O, Moghekar A, Wilson MR, Lah JJ, O'Brien RJ, Levey AI, Troncoso JC, Albert MS, Thambisetty M. Alpha-2 macroglobulin in Alzheimer's disease: a marker of neuronal injury through the RCAN1 pathway. Mol Psychiatry 2017; 22: 13-23 [PMID: 27872486 DOI: 10.1038/mp.2016.206]Kumar A, Singh A, Ekavali. A review on Alzheimer's disease pathophysiology and its management: an update. Pharmacol Rep 2015; 67: 195-203 [PMID: 25712639 DOI: 10.1016/j.pharep.2014.09.004]Hasegawa M. Molecular Mechanisms in the Pathogenesis of Alzheimer's disease and TauopathiesPrion-Like Seeded Aggregation and Phosphorylation. Biomolecules 2016; 6 [PMID: 27136595 DOI: 10.3390/biom6020024]Barbier P, Zejneli O, Martinho M, Lasorsa A, Belle V, Smet-Nocca C, Tsvetkov PO, Devred F, Landrieu I. Role of Tau as a Microtubule-Associated Protein: Structural and Functional Aspects. Front Aging Neurosci 2019; 11: 204 [PMID: 31447664 DOI: 10.3389/fnagi.2019.00204]Chesser AS, Pritchard SM, Johnson GV. Tau clearance mechanisms and their possible role in the pathogenesis of Alzheimer disease. Front Neurol 2013; 4: 122 [PMID: 24027553 DOI: 10.3389/fneur.2013.00122]Šimić G, Babić Leko M, Wray S, Harrington C, Delalle I, Jovanov-Milošević N, Bažadona D, Buée L, de Silva R, Di Giovanni G, Wischik C, Hof PR. Tau Protein Hyperphosphorylation and Aggregation in Alzheimer's Disease and Other Tauopathies, and Possible Neuroprotective Strategies. Biomolecules 2016; 6: 6 [PMID: 26751493 DOI: 10.3390/biom6010006]Tsartsalis S, Xekardaki A, Hof PR, Kövari E, Bouras C. Early Alzheimer-type lesions in cognitively normal subjects. Neurobiol Aging 2018; 62: 34-44 [PMID: 29107845 DOI: 10.1016/j.neurobiolaging.2017.10.002]Sonne DP, Hemmingsen B. Comment on American Diabetes Association. Standards of Medical Care in Diabetes-2017. Diabetes Care 2017;40(Suppl. 1):S1-S135. Diabetes Care 2017; 40: e92-e93 [PMID: 28637892 DOI: 10.2337/dc17-0299]Jayaraman A, Pike CJ. Alzheimer's disease and type 2 diabetes: multiple mechanisms contribute to interactions. Curr Diab Rep 2014; 14: 476 [PMID: 24526623 DOI: 10.1007/s11892-014-0476-2]Claxton A, Baker LD, Hanson A, Trittschuh EH, Cholerton B, Morgan A, Callaghan M, Arbuckle M, Behl C, Craft S. Long-acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer's disease dementia. J Alzheimers Dis 2015; 44: 897- 906 [PMID: 25374101 DOI: 10.3233/JAD-141791]Frölich L, Blum-Degen D, Bernstein HG, Engelsberger S, Humrich J, Laufer S, Muschner D, Thalheimer A, Türk A, Hoyer S, Zöchling R, Boissl KW, Jellinger K, Riederer P. Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease. J Neural Transm (Vienna) 1998; 105: 423-438 [PMID: 9720972 DOI: 10.1007/s007020050068]Craft S, Peskind E, Schwartz MW, Schellenberg GD, Raskind M, Porte D Jr. Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease: relationship to severity of dementia and apolipoprotein E genotype. Neurology 1998; 50: 164-168 [PMID: 9443474 DOI: 10.1212/wnl.50.1.164]Craft S, Asthana S, Schellenberg G, Baker L, Cherrier M, Boyt AA, Martins RN, Raskind M, Peskind E, Plymate S. Insulin effects on glucose metabolism, memory, and plasma amyloid precursor protein in Alzheimer's disease differ according to apolipoprotein-E genotype. Ann N Y Acad Sci 2000; 903: 222-228 [PMID: 10818510 DOI: 10.1111/j.1749-6632.2000.tb06371.x]Craft S, Asthana S, Cook DG, Baker LD, Cherrier M, Purganan K, Wait C, Petrova A, Latendresse S, Watson GS, Newcomer JW, Schellenberg GD, Krohn AJ. Insulin dose-response effects on memory and plasma amyloid precursor protein in Alzheimer's disease: interactions with apolipoprotein E genotype. Psychoneuroendocrinology 2003; 28: 809-822 [PMID: 12812866 DOI: 10.1016/s0306-4530(02)00087-2]Baker LD, Cross DJ, Minoshima S, Belongia D, Watson GS, Craft S. Insulin resistance and Alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes. Arch Neurol 2011; 68: 51-57 [PMID: 20837822 DOI: 10.1001/archneurol.2010.225]Femminella GD, Livingston NR, Raza S, van der Doef T, Frangou E, Love S, Busza G, Calsolaro V, Carver S, Holmes C, Ritchie CW, Lawrence RM, McFarlane B, Tadros G, Ridha BH, Bannister C, Walker Z, Archer H, Coulthard E, Underwood B, Prasanna A, Koranteng P, Karim S, Junaid K, McGuinness B, Passmore AP, Nilforooshan R, Macharouthu A, Donaldson A, Thacker S, Russell G, Malik N, Mate V, Knight L, Kshemendran S, Tan T, Holscher C, Harrison J, Brooks DJ, Ballard C, Edison P. Does insulin resistance influence neurodegeneration in non-diabetic Alzheimer's subjects? Alzheimers Res Ther 2021; 13: 47 [PMID: 33597002 DOI: 10.1186/s13195-021-00784-w]Thankappan S, Sen S, Subramanian S, Sinha P, Purushottam M, Bharath S. Insulin resistance in patients with Alzheimer's dementia: A controlled study from India. Asian J Psychiatr 2018; 38: 33- 34 [PMID: 30391679 DOI: 10.1016/j.ajp.2018.10.026]Ye F, Luo YJ, Xiao J, Yu NW, Yi G. Impact of Insulin Sensitizers on the Incidence of Dementia: A Meta-Analysis. Dement Geriatr Cogn Disord 2016; 41: 251-260 [PMID: 27250528 DOI: 10.1159/000445941]Watson KT, Wroolie TE, Tong G, Foland-Ross LC, Frangou S, Singh M, McIntyre RS, RoatShumway S, Myoraku A, Reiss AL, Rasgon NL. Neural correlates of liraglutide effects in persons at risk for Alzheimer's disease. Behav Brain Res 2019; 356: 271-278 [PMID: 30099030 DOI: 10.1016/j.bbr.2018.08.006]Koenig AM, Mechanic-Hamilton D, Xie SX, Combs MF, Cappola AR, Xie L, Detre JA, Wolk DA, Arnold SE. Effects of the Insulin Sensitizer Metformin in Alzheimer Disease: Pilot Data From a Randomized Placebo-controlled Crossover Study. Alzheimer Dis Assoc Disord 2017; 31: 107-113 [PMID: 28538088 DOI: 10.1097/WAD.0000000000000202]Kandimalla R, Thirumala V, Reddy PH. Is Alzheimer's disease a Type 3 Diabetes? Biochim Biophys Acta Mol Basis Dis 2017; 1863: 1078-1089 [PMID: 27567931 DOI: 10.1016/j.bbadis.2016.08.018]De Felice FG, Lourenco MV, Ferreira ST. How does brain insulin resistance develop in Alzheimer's disease? Alzheimers Dement 2014; 10: S26-S32 [PMID: 24529521 DOI: 10.1016/j.jalz.2013.12.004]Ahmad W. Overlapped metabolic and therapeutic links between Alzheimer and diabetes. Mol Neurobiol 2013; 47: 399-424 [PMID: 23011810 DOI: 10.1007/s12035-012-8352-z]De Felice FG, Ferreira ST. Inflammation, defective insulin signaling, and mitochondrial dysfunction as common molecular denominators connecting type 2 diabetes to Alzheimer disease. Diabetes 2014; 63: 2262-2272 [PMID: 24931033 DOI: 10.2337/db13-1954]Ansari SA, Emerald BS. The Role of Insulin Resistance and Protein O-GlcNAcylation in Neurodegeneration. Front Neurosci 2019; 13: 473 [PMID: 31143098 DOI: 10.3389/fnins.2019.00473]Mravec B, Horvathova L, Padova A. Brain Under Stress and Alzheimer's Disease. Cell Mol Neurobiol 2018; 38: 73-84 [PMID: 28699112 DOI: 10.1007/s10571-017-0521-1]Simó R, Ciudin A, Simó-Servat O, Hernández C. Cognitive impairment and dementia: a new emerging complication of type 2 diabetes-The diabetologist's perspective. Acta Diabetol 2017; 54: 417-424 [PMID: 28210868 DOI: 10.1007/s00592-017-0970-5]Shah K, Desilva S, Abbruscato T. The role of glucose transporters in brain disease: diabetes and Alzheimer’s Disease. Int J Mol Sci 2012; 13: 12629-12655 [PMID: 23202918 DOI: 10.3390/ijms131012629]Chen Z, Zhong C. Decoding Alzheimer's disease from perturbed cerebral glucose metabolism: implications for diagnostic and therapeutic strategies. Prog Neurobiol 2013; 108: 21-43 [PMID: 23850509 DOI: 10.1016/j.pneurobio.2013.06.004]Mooradian AD, Chung HC, Shah GN. GLUT-1 expression in the cerebra of patients with Alzheimer's disease. Neurobiol Aging 1997; 18: 469-474 [PMID: 9390772 DOI: 10.1016/s0197-4580(97)00111-5]Liu F, Shi J, Tanimukai H, Gu J, Grundke-Iqbal I, Iqbal K, Gong CX. Reduced O-GlcNAcylation links lower brain glucose metabolism and tau pathology in Alzheimer's disease. Brain 2009; 132: 1820-1832 [PMID: 19451179 DOI: 10.1093/brain/awp099]Liu Y, Liu F, Grundke-Iqbal I, Iqbal K, Gong CX. Brain glucose transporters, O-GlcNAcylation and phosphorylation of tau in diabetes and Alzheimer's disease. J Neurochem 2009; 111: 242-249 [PMID: 19659459 DOI: 10.1111/j.1471-4159.2009.06320.x]Liu Y, Liu F, Iqbal K, Grundke-Iqbal I, Gong CX. Decreased glucose transporters correlate to abnormal hyperphosphorylation of tau in Alzheimer disease. FEBS Lett 2008; 582: 359-364 [PMID: 18174027 DOI: 10.1016/j.febslet.2007.12.035]Simpson IA, Chundu KR, Davies-Hill T, Honer WG, Davies P. Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer's disease. Ann Neurol 1994; 35: 546-551 [PMID: 8179300 DOI: 10.1002/ana.410350507]Harr SD, Simonian NA, Hyman BT. Functional alterations in Alzheimer's disease: decreased glucose transporter 3 immunoreactivity in the perforant pathway terminal zone. J Neuropathol Exp Neurol 1995; 54: 38-41 [PMID: 7815078]Kann O, Kovács R. Mitochondria and neuronal activity. Am J Physiol Cell Physiol 2007; 292: C641-C657 [PMID: 17092996 DOI: 10.1152/ajpcell.00222.2006]Nunomura A, Honda K, Takeda A, Hirai K, Zhu X, Smith MA, Perry G. Oxidative damage to RNA in neurodegenerative diseases. J Biomed Biotechnol 2006; 2006: 82323 [PMID: 17047315 DOI: 10.1155/JBB/2006/82323]Correia SC, Santos RX, Carvalho C, Cardoso S, Candeias E, Santos MS, Oliveira CR, Moreira PI. Insulin signaling, glucose metabolism and mitochondria: major players in Alzheimer's disease and diabetes interrelation. Brain Res 2012; 1441: 64-78 [PMID: 22290178 DOI: 10.1016/j.brainres.2011.12.063]Butterfield DA, Di Domenico F, Barone E. Elevated risk of type 2 diabetes for development of Alzheimer disease: a key role for oxidative stress in brain. Biochim Biophys Acta 2014; 1842: 1693- 1706 [PMID: 24949886 DOI: 10.1016/j.bbadis.2014.06.010]Sorbi S, Bird ED, Blass JP. Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain. Ann Neurol 1983; 13: 72-78 [PMID: 6219611 DOI: 10.1002/ana.410130116]Butterworth RF, Besnard AM. Thiamine-dependent enzyme changes in temporal cortex of patients with Alzheimer's disease. Metab Brain Dis 1990; 5: 179-184 [PMID: 2087217 DOI: 10.1007/BF00997071]Yao J, Irwin RW, Zhao L, Nilsen J, Hamilton RT, Brinton RD. Mitochondrial bioenergetic deficit precedes Alzheimer's pathology in female mouse model of Alzheimer's disease. Proc Natl Acad Sci USA 2009; 106: 14670-14675 [PMID: 19667196 DOI: 10.1073/pnas.0903563106]Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, Johnson AB, Kress Y, Vinters HV, Tabaton M, Shimohama S, Cash AD, Siedlak SL, Harris PL, Jones PK, Petersen RB, Perry G, Smith MA. Mitochondrial abnormalities in Alzheimer's disease. J Neurosci 2001; 21: 3017-3023 [PMID: 11312286 DOI: 10.1523/JNEUROSCI.21-09-03017.2001]Parker WD Jr, Parks JK. Cytochrome c oxidase in Alzheimer's disease brain: purification and characterization. Neurology 1995; 45: 482-486 [PMID: 7898701 DOI: 10.1212/wnl.45.3.482]Sims NR, Finegan JM, Blass JP, Bowen DM, Neary D. Mitochondrial function in brain tissue in primary degenerative dementia. Brain Res 1987; 436: 30-38 [PMID: 3690351 DOI: 10.1016/0006-8993(87)91553-8]Bonda DJ, Wang X, Perry G, Smith MA, Zhu X. Mitochondrial dynamics in Alzheimer's disease: opportunities for future treatment strategies. Drugs Aging 2010; 27: 181-192 [PMID: 20210366 DOI: 10.2165/11532140-000000000-00000]Lloret A, Badía MC, Mora NJ, Ortega A, Pallardó FV, Alonso MD, Atamna H, Viña J. Gender and age-dependent differences in the mitochondrial apoptogenic pathway in Alzheimer's disease. Free Radic Biol Med 2008; 44: 2019-2025 [PMID: 18387371 DOI: 10.1016/j.freeradbiomed.2008.02.017]Devi L, Prabhu BM, Galati DF, Avadhani NG, Anandatheerthavarada HK. Accumulation of amyloid precursor protein in the mitochondrial import channels of human Alzheimer's disease brain is associated with mitochondrial dysfunction. J Neurosci 2006; 26: 9057-9068 [PMID: 16943564 DOI: 10.1523/JNEUROSCI.1469-06.2006]Cardoso SM, Santos S, Swerdlow RH, Oliveira CR. Functional mitochondria are required for amyloid beta-mediated neurotoxicity. FASEB J 2001; 15: 1439-1441 [PMID: 11387250 DOI: 10.1096/fj.00-0561fje]Du H, Guo L, Fang F, Chen D, Sosunov AA, McKhann GM, Yan Y, Wang C, Zhang H, Molkentin JD, Gunn-Moore FJ, Vonsattel JP, Arancio O, Chen JX, Yan SD. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nat Med 2008; 14: 1097-1105 [PMID: 18806802 DOI: 10.1038/nm.1868]Lustbader JW, Cirilli M, Lin C, Xu HW, Takuma K, Wang N, Caspersen C, Chen X, Pollak S, Chaney M, Trinchese F, Liu S, Gunn-Moore F, Lue LF, Walker DG, Kuppusamy P, Zewier ZL, Arancio O, Stern D, Yan SS, Wu H. ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease. Science 2004; 304: 448-452 [PMID: 15087549 DOI: 10.1126/science.1091230]Di Domenico F, Perluigi M, Butterfield DA, Cornelius C, Calabrese V. Oxidative damage in rat brain during aging: interplay between energy and metabolic key target proteins. Neurochem Res 2010; 35: 2184-2192 [PMID: 20963486 DOI: 10.1007/s11064-010-0295-z]Domínguez RO, Marschoff ER, González SE, Repetto MG, Serra JA. Type 2 diabetes and/or its treatment leads to less cognitive impairment in Alzheimer's disease patients. Diabetes Res Clin Pract 2012; 98: 68-74 [PMID: 22658669 DOI: 10.1016/j.diabres.2012.05.013]Butterfield DA, Lauderback CM. Lipid peroxidation and protein oxidation in Alzheimer's disease brain: potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress. Free Radic Biol Med 2002; 32: 1050-1060 [PMID: 12031889 DOI: 10.1016/s0891-5849(02)00794-3]Butterfield DA, Gu L, Di Domenico F, Robinson RA. Mass spectrometry and redox proteomics: applications in disease. Mass Spectrom Rev 2014; 33: 277-301 [PMID: 24930952 DOI: 10.1002/mas.21374]Moreira PI, Santos MS, Seiça R, Oliveira CR. Brain mitochondrial dysfunction as a link between Alzheimer's disease and diabetes. J Neurol Sci 2007; 257: 206-214 [PMID: 17316694 DOI: 10.1016/j.jns.2007.01.017]Maiese K, Chong ZZ, Shang YC. Mechanistic insights into diabetes mellitus and oxidative stress. Curr Med Chem 2007; 14: 1729-1738 [PMID: 17627510 DOI: 10.2174/092986707781058968]de la Monte SM. Insulin resistance and Alzheimer's disease. BMB Rep 2009; 42: 475-481 [PMID: 19712582 DOI: 10.5483/bmbrep.2009.42.8.475]de la Monte SM, Tong M. Brain metabolic dysfunction at the core of Alzheimer's disease. Biochem Pharmacol 2014; 88: 548-559 [PMID: 24380887 DOI: 10.1016/j.bcp.2013.12.012]Orth M, Schapira AH. Mitochondria and degenerative disorders. Am J Med Genet 2001; 106: 27-36 [PMID: 11579422 DOI: 10.1002/ajmg.1425]Klionsky DJ. The molecular machinery of autophagy: unanswered questions. J Cell Sci 2005; 118: 7-18 [PMID: 15615779 DOI: 10.1242/jcs.01620]Gonzalez CD, Lee MS, Marchetti P, Pietropaolo M, Towns R, Vaccaro MI, Watada H, Wiley JW. The emerging role of autophagy in the pathophysiology of diabetes mellitus. Autophagy 2011; 7: 2- 11 [PMID: 20935516 DOI: 10.4161/auto.7.1.13044]Caberlotto L, Nguyen TP, Lauria M, Priami C, Rimondini R, Maioli S, Cedazo-Minguez A, Sita G, Morroni F, Corsi M, Carboni L. Cross-disease analysis of Alzheimer's disease and type-2 Diabetes highlights the role of autophagy in the pathophysiology of two highly comorbid diseases. Sci Rep 2019; 9: 3965 [PMID: 30850634 DOI: 10.1038/s41598-019-39828-5]Whyte LS, Lau AA, Hemsley KM, Hopwood JJ, Sargeant TJ. Endo-lysosomal and autophagic dysfunction: a driving factor in Alzheimer's disease? J Neurochem 2017; 140: 703-717 [PMID: 28027395 DOI: 10.1111/jnc.13935]Barlow AD, Thomas DC. Autophagy in diabetes: β-cell dysfunction, insulin resistance, and complications. DNA Cell Biol 2015; 34: 252-260 [PMID: 25665094 DOI: 10.1089/dna.2014.2755]Lee YH, Kim J, Park K, Lee MS. β-cell autophagy: Mechanism and role in β-cell dysfunction. Mol Metab 2019; 27S: S92-S103 [PMID: 31500836 DOI: 10.1016/j.molmet.2019.06.014]Herzig S, Shaw RJ. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol 2018; 19: 121-135 [PMID: 28974774 DOI: 10.1038/nrm.2017.95]Saxton RA, Sabatini DM. mTOR Signaling in Growth, Metabolism, and Disease. Cell 2017; 168: 960-976 [PMID: 28283069 DOI: 10.1016/j.cell.2017.02.004]Lee JA. Neuronal autophagy: a housekeeper or a fighter in neuronal cell survival? Exp Neurobiol 2012; 21: 1-8 [PMID: 22438673 DOI: 10.5607/en.2012.21.1.1]Frake RA, Ricketts T, Menzies FM, Rubinsztein DC. Autophagy and neurodegeneration. J Clin Invest 2015; 125: 65-74 [PMID: 25654552 DOI: 10.1172/JCI73944]Harris H, Rubinsztein DC. Control of autophagy as a therapy for neurodegenerative disease. Nat Rev Neurol 2011; 8: 108-117 [PMID: 22187000 DOI: 10.1038/nrneurol.2011.200]Sun B, Zhou Y, Halabisky B, Lo I, Cho SH, Mueller-Steiner S, Devidze N, Wang X, Grubb A, Gan L. Cystatin C-cathepsin B axis regulates amyloid beta levels and associated neuronal deficits in an animal model of Alzheimer's disease. Neuron 2008; 60: 247-257 [PMID: 18957217 DOI: 10.1016/j.neuron.2008.10.001]Yang DS, Stavrides P, Mohan PS, Kaushik S, Kumar A, Ohno M, Schmidt SD, Wesson D, Bandyopadhyay U, Jiang Y, Pawlik M, Peterhoff CM, Yang AJ, Wilson DA, St George-Hyslop P, Westaway D, Mathews PM, Levy E, Cuervo AM, Nixon RA. Reversal of autophagy dysfunction in the TgCRND8 mouse model of Alzheimer's disease ameliorates amyloid pathologies and memory deficits. Brain 2011; 134: 258-277 [PMID: 21186265 DOI: 10.1093/brain/awq341]Lee JH, Yu WH, Kumar A, Lee S, Mohan PS, Peterhoff CM, Wolfe DM, Martinez-Vicente M, Massey AC, Sovak G, Uchiyama Y, Westaway D, Cuervo AM, Nixon RA. Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell 2010; 141: 1146-1158 [PMID: 20541250 DOI: 10.1016/j.cell.2010.05.008]Boland B, Kumar A, Lee S, Platt FM, Wegiel J, Yu WH, Nixon RA. Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer's disease. J Neurosci 2008; 28: 6926-6937 [PMID: 18596167 DOI: 10.1523/JNEUROSCI.0800-08.2008]Pickford F, Masliah E, Britschgi M, Lucin K, Narasimhan R, Jaeger PA, Small S, Spencer B, Rockenstein E, Levine B, Wyss-Coray T. The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice. J Clin Invest 2008; 118: 2190-2199 [PMID: 18497889 DOI: 10.1172/JCI33585]Correia SC, Perry G, Moreira PI. Mitochondrial traffic jams in Alzheimer's disease - pinpointing the roadblocks. Biochim Biophys Acta 2016; 1862: 1909-1917 [PMID: 27460705 DOI: 10.1016/j.bbadis.2016.07.010]Kerr JS, Adriaanse BA, Greig NH, Mattson MP, Cader MZ, Bohr VA, Fang EF. Mitophagy and Alzheimer's Disease: Cellular and Molecular Mechanisms. Trends Neurosci 2017; 40: 151-166 [PMID: 28190529 DOI: 10.1016/j.tins.2017.01.002]Nixon RA, Yang DS. Autophagy failure in Alzheimer's disease--locating the primary defect. Neurobiol Dis 2011; 43: 38-45 [PMID: 21296668 DOI: 10.1016/j.nbd.2011.01.021]Vagelatos NT, Eslick GD. Type 2 diabetes as a risk factor for Alzheimer's disease: the confounders, interactions, and neuropathology associated with this relationship. Epidemiol Rev 2013; 35: 152-160 [PMID: 23314404 DOI: 10.1093/epirev/mxs012]Gudala K, Bansal D, Schifano F, Bhansali A. Diabetes mellitus and risk of dementia: A metaanalysis of prospective observational studies. J Diabetes Investig 2013; 4: 640-650 [PMID: 24843720 DOI: 10.1111/jdi.12087]Profenno LA, Porsteinsson AP, Faraone SV. Meta-analysis of Alzheimer's disease risk with obesity, diabetes, and related disorders. Biol Psychiatry 2010; 67: 505-512 [PMID: 19358976 DOI: 10.1016/j.biopsych.2009.02.013]Ohara T, Doi Y, Ninomiya T, Hirakawa Y, Hata J, Iwaki T, Kanba S, Kiyohara Y. Glucose tolerance status and risk of dementia in the community: the Hisayama study. Neurology 2011; 77: 1126-1134 [PMID: 21931106 DOI: 10.1212/WNL.0b013e31822f0435]Xu WL, von Strauss E, Qiu CX, Winblad B, Fratiglioni L. Uncontrolled diabetes increases the risk of Alzheimer's disease: a population-based cohort study. Diabetologia 2009; 52: 1031-1039 [PMID: 19280172 DOI: 10.1007/s00125-009-1323-x]Xu WL, Qiu CX, Wahlin A, Winblad B, Fratiglioni L. Diabetes mellitus and risk of dementia in the Kungsholmen project: a 6-year follow-up study. Neurology 2004; 63: 1181-1186 [PMID: 15477535 DOI: 10.1212/01.wnl.0000140291.86406.d1]Peila R, Rodriguez BL, Launer LJ; Honolulu-Asia Aging Study. Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study. Diabetes 2002; 51: 1256-1262 [PMID: 11916953 DOI: 10.2337/diabetes.51.4.1256]McIntosh EC, Nation DA; Alzheimer’s Disease Neuroimaging Initiative. Importance of Treatment Status in Links Between Type 2 Diabetes and Alzheimer's Disease. Diabetes Care 2019; 42: 972- 979 [PMID: 30833374 DOI: 10.2337/dc18-1399]Ahtiluoto S, Polvikoski T, Peltonen M, Solomon A, Tuomilehto J, Winblad B, Sulkava R, Kivipelto M. Diabetes, Alzheimer disease, and vascular dementia: a population-based neuropathologic study. Neurology 2010; 75: 1195-1202 [PMID: 20739645 DOI: 10.1212/WNL.0b013e3181f4d7f8]Matsuzaki T, Sasaki K, Tanizaki Y, Hata J, Fujimi K, Matsui Y, Sekita A, Suzuki SO, Kanba S, Kiyohara Y, Iwaki T. Insulin resistance is associated with the pathology of Alzheimer disease: the Hisayama study. Neurology 2010; 75: 764-770 [PMID: 20739649 DOI: 10.1212/WNL.0b013e3181eee25f]American Diabetes Association. . 5. Lifestyle Management: Standards of Medical Care in Diabetes-2019. Diabetes Care 2019; 42: S46-S60 [PMID: 30559231 DOI: 10.2337/dc19-S005]Dunkley AJ, Bodicoat DH, Greaves CJ, Russell C, Yates T, Davies MJ, Khunti K. Diabetes prevention in the real world: effectiveness of pragmatic lifestyle interventions for the prevention of type 2 diabetes and of the impact of adherence to guideline recommendations: a systematic review and meta-analysis. Diabetes Care 2014; 37: 922-933 [PMID: 24652723 DOI: 10.2337/dc13-2195]Schellenberg ES, Dryden DM, Vandermeer B, Ha C, Korownyk C. Lifestyle interventions for patients with and at risk for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med 2013; 159: 543-551 [PMID: 24126648 DOI: 10.7326/0003-4819-159-8-201310150-00007]Bhatti GK, Reddy AP, Reddy PH, Bhatti JS. Lifestyle Modifications and Nutritional Interventions in Aging-Associated Cognitive Decline and Alzheimer's Disease. Front Aging Neurosci 2019; 11: 369 [PMID: 31998117 DOI: 10.3389/fnagi.2019.00369]Bayer-Carter JL, Green PS, Montine TJ, VanFossen B, Baker LD, Watson GS, Bonner LM, Callaghan M, Leverenz JB, Walter BK, Tsai E, Plymate SR, Postupna N, Wilkinson CW, Zhang J, Lampe J, Kahn SE, Craft S. Diet intervention and cerebrospinal fluid biomarkers in amnestic mild cognitive impairment. Arch Neurol 2011; 68: 743-752 [PMID: 21670398 DOI: 10.1001/archneurol.2011.125]Dhana K, Evans DA, Rajan KB, Bennett DA, Morris MC. Healthy lifestyle and the risk of Alzheimer dementia: Findings from 2 Longitudinal studies. Neurology 2020; 95: e374-e383 [PMID: 32554763 DOI: 10.1212/WNL.0000000000009816]Kern W, Peters A, Fruehwald-Schultes B, Deininger E, Born J, Fehm HL. Improving influence of insulin on cognitive functions in humans. Neuroendocrinology 2001; 74: 270-280 [PMID: 11598383 DOI: 10.1159/000054694]Craft S, Asthana S, Newcomer JW, Wilkinson CW, Matos IT, Baker LD, Cherrier M, Lofgreen C, Latendresse S, Petrova A, Plymate S, Raskind M, Grimwood K, Veith RC. Enhancement of memory in Alzheimer disease with insulin and somatostatin, but not glucose. Arch Gen Psychiatry 1999; 56: 1135-1140 [PMID: 10591291 DOI: 10.1001/archpsyc.56.12.1135]Craft S, Newcomer J, Kanne S, Dagogo-Jack S, Cryer P, Sheline Y, Luby J, Dagogo-Jack A, Alderson A. Memory improvement following induced hyperinsulinemia in Alzheimer's disease. Neurobiol Aging 1996; 17: 123-130 [PMID: 8786794 DOI: 10.1016/0197-4580(95)02002-0]McCall AL. Insulin therapy and hypoglycemia. Endocrinol Metab Clin North Am 2012; 41: 57-87 [PMID: 22575407 DOI: 10.1016/j.ecl.2012.03.001]Herman ME, O'Keefe JH, Bell DSH, Schwartz SS. Insulin Therapy Increases Cardiovascular Risk in Type 2 Diabetes. Prog Cardiovasc Dis 2017; 60: 422-434 [PMID: 28958751 DOI: 10.1016/j.pcad.2017.09.001]Margolis DJ, Hoffstad O, Strom BL. Association between serious ischemic cardiac outcomes and medications used to treat diabetes. Pharmacoepidemiol Drug Saf 2008; 17: 753-759 [PMID: 18613215 DOI: 10.1002/pds.1630]Graveling AJ, Deary IJ, Frier BM. Acute hypoglycemia impairs executive cognitive function in adults with and without type 1 diabetes. Diabetes Care 2013; 36: 3240-3246 [PMID: 23780950 DOI: 10.2337/dc13-0194]Lacy ME, Gilsanz P, Eng C, Beeri MS, Karter AJ, Whitmer RA. Severe Hypoglycemia and Cognitive Function in Older Adults With Type 1 Diabetes: The Study of Longevity in Diabetes (SOLID). Diabetes Care 2020; 43: 541-548 [PMID: 31882410 DOI: 10.2337/dc19-0906]Weinstein G, Davis-Plourde KL, Conner S, Himali JJ, Beiser AS, Lee A, Rawlings AM, Sedaghat S, Ding J, Moshier E, van Duijn CM, Beeri MS, Selvin E, Ikram MA, Launer LJ, Haan MN, Seshadri S. Association of metformin, sulfonylurea and insulin use with brain structure and function and risk of dementia and Alzheimer's disease: Pooled analysis from 5 cohorts. PLoS One 2019; 14: e0212293 [PMID: 30768625 DOI: 10.1371/journal.pone.0212293]Verdile G, Fuller SJ, Martins RN. The role of type 2 diabetes in neurodegeneration. Neurobiol Dis 2015; 84: 22-38 [PMID: 25926349 DOI: 10.1016/j.nbd.2015.04.008]Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, Arbuckle M, Callaghan M, Tsai E, Plymate SR, Green PS, Leverenz J, Cross D, Gerton B. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol 2012; 69: 29-38 [PMID: 21911655 DOI: 10.1001/archneurol.2011.233]Reger MA, Watson GS, Frey WH 2nd, Baker LD, Cholerton B, Keeling ML, Belongia DA, Fishel MA, Plymate SR, Schellenberg GD, Cherrier MM, Craft S. Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype. Neurobiol Aging 2006; 27: 451- 458 [PMID: 15964100 DOI: 10.1016/j.neurobiolaging.2005.03.016]Benedict C, Hallschmid M, Schmitz K, Schultes B, Ratter F, Fehm HL, Born J, Kern W. Intranasal insulin improves memory in humans: superiority of insulin aspart. Neuropsychopharmacology 2007; 32: 239-243 [PMID: 16936707 DOI: 10.1038/sj.npp.1301193]Reger MA, Watson GS, Green PS, Wilkinson CW, Baker LD, Cholerton B, Fishel MA, Plymate SR, Breitner JC, DeGroodt W, Mehta P, Craft S. Intranasal insulin improves cognition and modulates beta-amyloid in early AD. Neurology 2008; 70: 440-448 [PMID: 17942819 DOI: 10.1212/01.WNL.0000265401.62434.36]Craft S, Raman R, Chow TW, Rafii MS, Rissman RA, Brewer JB, Donohue MC, Sun C-K, Harless K, Gessert D, Aisen PS. DT-02-03: Open label extension results from a phase ii/iii trial of intranasal insulin. Alzheimers Dement 2019; 15: P1489-P1489 [DOI: 10.1016/j.jalz.2019.08.012]Craft S. Study of Nasal Insulin to Fight Forgetfulness - Short-Acting Insulin Aspart (SNIFFQuick). [accessed 2020 Dec 19]. In: ClinicalTrials.gov [Internet]. Winston-Salem (CA): U.S. National Library of Medicine. Available from: https://www.clinicaltrials.gov/ct2/show/NCT02462161 ClinicalTrials.gov Identifier: NCT02462161Rosenbloom MH. Intranasal Glulisine in Amnestic Mild Cognitive Impairment and Probable Mild Alzheimer's Disease. [accessed 2020 Dec 16]. In: ClinicalTrials.gov [Internet]. Saint Paul (MN): U.S. National Library of Medicine. Available from: https://clinicaltrials.gov/ct2/show/NCT02503501 ClinicalTrials.gov Identifier: NCT02503501de Candia P, Matarese G. Leptin and ghrelin: Sewing metabolism onto neurodegeneration. Neuropharmacology 2018; 136: 307-316 [PMID: 29248481 DOI: 10.1016/j.neuropharm.2017.12.025]McGuire MJ, Ishii M. Leptin Dysfunction and Alzheimer's Disease: Evidence from Cellular, Animal, and Human Studies. Cell Mol Neurobiol 2016; 36: 203-217 [PMID: 26993509 DOI: 10.1007/s10571-015-0282-7]Salazar J, Chávez-Castillo M, Rojas J, Ortega A, Nava M, Pérez J, Rojas M, Espinoza C, Chacin M, Herazo Y, Angarita L, Rojas DM, D'Marco L, Bermudez V. Is "Leptin Resistance" Another Key Resistance to Manage Type 2 Diabetes? Curr Diabetes Rev 2020; 16: 733-749 [PMID: 31886750 DOI: 10.2174/1573399816666191230111838]Tezapsidis N, Johnston JM, Smith MA, Ashford JW, Casadesus G, Robakis NK, Wolozin B, Perry G, Zhu X, Greco SJ, Sarkar S. Leptin: a novel therapeutic strategy for Alzheimer's disease. J Alzheimers Dis 2009; 16: 731-740 [PMID: 19387109 DOI: 10.3233/JAD-2009-1021]Frühbeck G. Intracellular signalling pathways activated by leptin. Biochem J 2006; 393: 7-20 [PMID: 16336196 DOI: 10.1042/BJ20051578]Paz-Filho G, Mastronardi C, Wong ML, Licinio J. Leptin therapy, insulin sensitivity, and glucose homeostasis. Indian J Endocrinol Metab 2012; 16: S549-S555 [PMID: 23565489 DOI: 10.4103/2230-8210.105571]German JP, Wisse BE, Thaler JP, Oh-I S, Sarruf DA, Ogimoto K, Kaiyala KJ, Fischer JD, Matsen ME, Taborsky GJ Jr, Schwartz MW, Morton GJ. Leptin deficiency causes insulin resistance induced by uncontrolled diabetes. Diabetes 2010; 59: 1626-1634 [PMID: 20424233 DOI: 10.2337/db09-1918]Harvey J, Solovyova N, Irving A. Leptin and its role in hippocampal synaptic plasticity. Prog Lipid Res 2006; 45: 369-378 [PMID: 16678906 DOI: 10.1016/j.plipres.2006.03.001]Greco SJ, Bryan KJ, Sarkar S, Zhu X, Smith MA, Ashford JW, Johnston JM, Tezapsidis N, Casadesus G. Leptin reduces pathology and improves memory in a transgenic mouse model of Alzheimer's disease. J Alzheimers Dis 2010; 19: 1155-1167 [PMID: 20308782 DOI: 10.3233/JAD-2010-1308]Pérez-González R, Antequera D, Vargas T, Spuch C, Bolós M, Carro E. Leptin induces proliferation of neuronal progenitors and neuroprotection in a mouse model of Alzheimer's disease. J Alzheimers Dis 2011; 24 Suppl 2: 17-25 [PMID: 21335656 DOI: 10.3233/JAD-2011-102070]Gómez R, Lago F, Gómez-Reino JJ, Gualillo O. Novel factors as therapeutic targets to treat diabetes. Focus on leptin and ghrelin. Expert Opin Ther Targets 2009; 13: 583-591 [PMID: 19397477 DOI: 10.1517/14728220902914834]Seminara RS, Jeet C, Biswas S, Kanwal B, Iftikhar W, Sakibuzzaman M, Rutkofsky IH. The Neurocognitive Effects of Ghrelin-induced Signaling on the Hippocampus: A Promising Approach to Alzheimer's Disease. Cureus 2018; 10: e3285 [PMID: 30443455 DOI: 10.7759/cureus.3285]Kern A, Mavrikaki M, Ullrich C, Albarran-Zeckler R, Brantley AF, Smith RG. Hippocampal Dopamine/DRD1 Signaling Dependent on the Ghrelin Receptor. Cell 2015; 163: 1176-1190 [PMID: 26590421 DOI: 10.1016/j.cell.2015.10.062]Tian J, Guo L, Sui S, Driskill C, Phensy A, Wang Q, Gauba E, Zigman JM, Swerdlow RH, Kroener S, Du H. Disrupted hippocampal growth hormone secretagogue receptor 1α interaction with dopamine receptor D1 plays a role in Alzheimer's disease. Sci Transl Med 2019; 11 [PMID: 31413143 DOI: 10.1126/scitranslmed.aav6278]Kunath N, van Groen T, Allison DB, Kumar A, Dozier-Sharpe M, Kadish I. Ghrelin agonist does not foster insulin resistance but improves cognition in an Alzheimer's disease mouse model. Sci Rep 2015; 5: 11452 [PMID: 26090621 DOI: 10.1038/srep11452]Chen Y, Cao CP, Li CR, Wang W, Zhang D, Han LL, Zhang XQ, Kim A, Kim S, Liu GL. Ghrelin modulates insulin sensitivity and tau phosphorylation in high glucose-induced hippocampal neurons. Biol Pharm Bull 2010; 33: 1165-1169 [PMID: 20606308 DOI: 10.1248/bpb.33.1165]Dhurandhar EJ, Allison DB, van Groen T, Kadish I. Hunger in the absence of caloric restriction improves cognition and attenuates Alzheimer's disease pathology in a mouse model. PLoS One 2013; 8: e60437 [PMID: 23565247 DOI: 10.1371/journal.pone.0060437]Eslami M, Sadeghi B, Goshadrou F. Chronic ghrelin administration restores hippocampal long-term potentiation and ameliorates memory impairment in rat model of Alzheimer's disease. Hippocampus 2018; 28: 724-734 [PMID: 30009391 DOI: 10.1002/hipo.23002]Santos VV, Stark R, Rial D, Silva HB, Bayliss JA, Lemus MB, Davies JS, Cunha RA, Prediger RD, Andrews ZB. Acyl ghrelin improves cognition, synaptic plasticity deficits and neuroinflammation following amyloid β (Aβ1-40) administration in mice. J Neuroendocrinol 2017; 29 [PMID: 28380673 DOI: 10.1111/jne.12476]Hsu CC, Wahlqvist ML, Lee MS, Tsai HN. Incidence of dementia is increased in type 2 diabetes and reduced by the use of sulfonylureas and metformin. J Alzheimers Dis 2011; 24: 485-493 [PMID: 21297276 DOI: 10.3233/JAD-2011-101524]Alp H, Varol S, Celik MM, Altas M, Evliyaoglu O, Tokgoz O, Tanrıverdi MH, Uzar E. Protective effects of beta glucan and gliclazide on brain tissue and sciatic nerve of diabetic rats induced by streptozosin. Exp Diabetes Res 2012; 2012: 230342 [PMID: 22291696 DOI: 10.1155/2012/230342]Baraka A, ElGhotny S. Study of the effect of inhibiting galanin in Alzheimer's disease induced in rats. Eur J Pharmacol 2010; 641: 123-127 [PMID: 20639139 DOI: 10.1016/j.ejphar.2010.05.030]Abdallah DM, Nassar NN, Abd-El-Salam RM. Glibenclamide ameliorates ischemia-reperfusion injury via modulating oxidative stress and inflammatory mediators in the rat hippocampus. Brain Res 2011; 1385: 257-262 [PMID: 21316351 DOI: 10.1016/j.brainres.2011.02.007]Schloot NC, Haupt A, Schütt M, Badenhoop K, Laimer M, Nicolay C, Reaney M, Fink K, Holl RW. Risk of severe hypoglycemia in sulfonylurea-treated patients from diabetes centers in Germany/Austria: How big is the problem? Diabetes Metab Res Rev 2016; 32: 316-324 [PMID: 26409039 DOI: 10.1002/dmrr.2722]Schopman JE, Simon AC, Hoefnagel SJ, Hoekstra JB, Scholten RJ, Holleman F. The incidence of mild and severe hypoglycaemia in patients with type 2 diabetes mellitus treated with sulfonylureas: a systematic review and meta-analysis. Diabetes Metab Res Rev 2014; 30: 11-22 [PMID: 24030920 DOI: 10.1002/dmrr.2470]Kickstein E, Krauss S, Thornhill P, Rutschow D, Zeller R, Sharkey J, Williamson R, Fuchs M, Köhler A, Glossmann H, Schneider R, Sutherland C, Schweiger S. Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling. Proc Natl Acad Sci USA 2010; 107: 21830-21835 [PMID: 21098287 DOI: 10.1073/pnas.0912793107]Li SN, Wang X, Zeng QT, Feng YB, Cheng X, Mao XB, Wang TH, Deng HP. Metformin inhibits nuclear factor kappaB activation and decreases serum high-sensitivity C-reactive protein level in experimental atherogenesis of rabbits. Heart Vessels 2009; 24: 446-453 [PMID: 20108078 DOI: 10.1007/s00380-008-1137-7]Rena G, Pearson ER, Sakamoto K. Molecular mechanism of action of metformin: old or new insights? Diabetologia 2013; 56: 1898-1906 [PMID: 23835523 DOI: 10.1007/s00125-013-2991-0]Burcelin R. The antidiabetic gutsy role of metformin uncovered? Gut 2014; 63: 706-707 [PMID: 23840042 DOI: 10.1136/gutjnl-2013-305370]Ibrahim OHM, Hassan MA. The Use of Anti-Diabetic Drugs in Alzheimer’s Disease, New Therapeutic Options and Future Perspective. Pharmacol Amp Pharm 2018; 9: 157-174 [DOI: 10.4236/pp.2018.96013]Mostafa DK, Ismail CA, Ghareeb DA. Differential metformin dose-dependent effects on cognition in rats: role of Akt. Psychopharmacology (Berl) 2016; 233: 2513-2524 [PMID: 27113224 DOI: 10.1007/s00213-016-4301-2]Imfeld P, Bodmer M, Jick SS, Meier CR. Metformin, other antidiabetic drugs, and risk of Alzheimer's disease: a population-based case-control study. J Am Geriatr Soc 2012; 60: 916-921 [PMID: 22458300 DOI: 10.1111/j.1532-5415.2012.03916.x]Wang L, Liu W, Fan Y, Liu T, Yu C. Effect of rosiglitazone on amyloid precursor protein processing and Aβ clearance in streptozotocin-induced rat model of Alzheimer's disease. Iran J Basic Med Sci 2017; 20: 474-480 [PMID: 28656081 DOI: 10.22038/IJBMS.2017.8669]Pancani T, Phelps JT, Searcy JL, Kilgore MW, Chen KC, Porter NM, Thibault O. Distinct modulation of voltage-gated and ligand-gated Ca2+ currents by PPAR-gamma agonists in cultured hippocampal neurons. J Neurochem 2009; 109: 1800-1811 [PMID: 19453298 DOI: 10.1111/j.1471-4159.2009.06107.x]Femminella GD, Bencivenga L, Petraglia L, Visaggi L, Gioia L, Grieco FV, de Lucia C, Komici K, Corbi G, Edison P, Rengo G, Ferrara N. Antidiabetic Drugs in Alzheimer's Disease: Mechanisms of Action and Future Perspectives. J Diabetes Res 2017; 2017: 7420796 [PMID: 28656154 DOI: 10.1155/2017/7420796]Cheng H, Shang Y, Jiang L, Shi TL, Wang L. The peroxisome proliferators activated receptorgamma agonists as therapeutics for the treatment of Alzheimer's disease and mild-to-moderate Alzheimer's disease: a meta-analysis. Int J Neurosci 2016; 126: 299-307 [PMID: 26001206 DOI: 10.3109/00207454.2015.1015722]Sato T, Hanyu H, Hirao K, Kanetaka H, Sakurai H, Iwamoto T. Efficacy of PPAR-γ agonist pioglitazone in mild Alzheimer disease. Neurobiol Aging 2011; 32: 1626-1633 [PMID: 19923038 DOI: 10.1016/j.neurobiolaging.2009.10.009]Geldmacher DS, Fritsch T, McClendon MJ, Landreth G. A randomized pilot clinical trial of the safety of pioglitazone in treatment of patients with Alzheimer disease. Arch Neurol 2011; 68: 45-50 [PMID: 20837824 DOI: 10.1001/archneurol.2010.229]Takeda. Biomarker Qualification for Risk of Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease (AD) and Safety and Efficacy Evaluation of Pioglitazone in Delaying Its Onset (TOMMORROW). [accessed 2020 Dec 20]. In: ClinicalTrials.gov [Internet]. Zinfandel Pharmaceuticals Inc.: U.S. National Library of Medicine. Available from: https://clinicaltrials.gov/ct2/show/NCT01931566 ClinicalTrials.gov Identifier: NCT01931566Hölscher C. Central effects of GLP-1: new opportunities for treatments of neurodegenerative diseases. J Endocrinol 2014; 221: T31-T41 [PMID: 23999914 DOI: 10.1530/JOE-13-0221]McClean PL, Parthsarathy V, Faivre E, Hölscher C. The diabetes drug liraglutide prevents degenerative processes in a mouse model of Alzheimer's disease. J Neurosci 2011; 31: 6587-6594 [PMID: 21525299 DOI: 10.1523/JNEUROSCI.0529-11.2011]Han WN, Hölscher C, Yuan L, Yang W, Wang XH, Wu MN, Qi JS. Liraglutide protects against amyloid-β protein-induced impairment of spatial learning and memory in rats. Neurobiol Aging 2013; 34: 576-588 [PMID: 22592020 DOI: 10.1016/j.neurobiolaging.2012.04.009]Parthsarathy V, Hölscher C. Chronic treatment with the GLP1 analogue liraglutide increases cell proliferation and differentiation into neurons in an AD mouse model. PLoS One 2013; 8: e58784 [PMID: 23536825 DOI: 10.1371/journal.pone.0058784]Kelly P, McClean PL, Ackermann M, Konerding MA, Hölscher C, Mitchell CA. Restoration of cerebral and systemic microvascular architecture in APP/PS1 transgenic mice following treatment with Liraglutide™. Microcirculation 2015; 22: 133-145 [PMID: 25556713 DOI: 10.1111/micc.12186]Qi L, Ke L, Liu X, Liao L, Ke S, Wang Y, Lin X, Zhou Y, Wu L, Chen Z, Liu L. Subcutaneous administration of liraglutide ameliorates learning and memory impairment by modulating tau hyperphosphorylation via the glycogen synthase kinase-3β pathway in an amyloid β protein induced alzheimer disease mouse model. Eur J Pharmacol 2016; 783: 23-32 [PMID: 27131827 DOI: 10.1016/j.ejphar.2016.04.052]Gejl M, Gjedde A, Egefjord L, Møller A, Hansen SB, Vang K, Rodell A, Brændgaard H, Gottrup H, Schacht A, Møller N, Brock B, Rungby J. In Alzheimer's Disease, 6-Month Treatment with GLP-1 Analog Prevents Decline of Brain Glucose Metabolism: Randomized, Placebo-Controlled, DoubleBlind Clinical Trial. Front Aging Neurosci 2016; 8: 108 [PMID: 27252647 DOI: 10.3389/fnagi.2016.00108]Edison P. Evaluating Liraglutide in Alzheimer's Disease (ELAD). [accessed 2020 Dec 19]. In: ClinicalTrials.gov [Internet]. London: U.S. National Library of Medicine. Available from: https://clinicaltrials.gov/ct2/show/NCT01843075 ClinicalTrials.gov Identifier: NCT01843075Gault VA, Hölscher C. Protease-resistant glucose-dependent insulinotropic polypeptide agonists facilitate hippocampal LTP and reverse the impairment of LTP induced by beta-amyloid. JNeurophysiol 2008; 99: 1590-1595 [PMID: 18234983 DOI: 10.1152/jn.01161.2007]Duffy AM, Hölscher C. The incretin analogue D-Ala2GIP reduces plaque load, astrogliosis and oxidative stress in an APP/PS1 mouse model of Alzheimer's disease. Neuroscience 2013; 228: 294- 300 [PMID: 23103794 DOI: 10.1016/j.neuroscience.2012.10.045]Faivre E, Hölscher C. Neuroprotective effects of D-Ala(2)GIP on Alzheimer's disease biomarkers in an APP/PS1 mouse model. Alzheimers Res Ther 2013; 5: 20 [PMID: 23601582 DOI: 10.1186/alzrt174]Hölscher C. Novel dual GLP-1/GIP receptor agonists show neuroprotective effects in Alzheimer's and Parkinson's disease models. Neuropharmacology 2018; 136: 251-259 [PMID: 29402504 DOI: 10.1016/j.neuropharm.2018.01.040]Li T, Jiao JJ, Hölscher C, Wu MN, Zhang J, Tong JQ, Dong XF, Qu XS, Cao Y, Cai HY, Su Q, Qi JS. A novel GLP-1/GIP/Gcg triagonist reduces cognitive deficits and pathology in the 3xTg mouse model of Alzheimer's disease. Hippocampus 2018; 28: 358-372 [PMID: 29473979 DOI: 10.1002/hipo.22837]Camins A, Ettcheto M, Busquets O, Manzine PR, Castro-Torres RD, Beas-Zarate C, Verdaguer E, Sureda FX, Bulló M, Olloquequi J, Auladell C, Folch J. Triple GLP-1/GIP/glucagon receptor agonists, a potential novel treatment strategy in Alzheimer's disease. Expert Opin Investig Drugs 2019; 28: 93-97 [PMID: 30480461 DOI: 10.1080/13543784.2019.1552677]Kosaraju J, Gali CC, Khatwal RB, Dubala A, Chinni S, Holsinger RM, Madhunapantula VS, Muthureddy Nataraj SK, Basavan D. Saxagliptin: a dipeptidyl peptidase-4 inhibitor ameliorates streptozotocin induced Alzheimer's disease. Neuropharmacology 2013; 72: 291-300 [PMID: 23603201 DOI: 10.1016/j.neuropharm.2013.04.008]Kosaraju J, Murthy V, Khatwal RB, Dubala A, Chinni S, Muthureddy Nataraj SK, Basavan D. Vildagliptin: an anti-diabetes agent ameliorates cognitive deficits and pathology observed in streptozotocin-induced Alzheimer's disease. J Pharm Pharmacol 2013; 65: 1773-1784 [PMID: 24117480 DOI: 10.1111/jphp.12148]Wiciński M, Wódkiewicz E, Górski K, Walczak M, Malinowski B. Perspective of SGLT2 Inhibition in Treatment of Conditions Connected to Neuronal Loss: Focus on Alzheimer's Disease and Ischemia-Related Brain Injury. Pharmaceuticals (Basel) 2020; 13 [PMID: 33187206 DOI: 10.3390/ph13110379]Sa-Nguanmoo P, Tanajak P, Kerdphoo S, Jaiwongkam T, Pratchayasakul W, Chattipakorn N, Chattipakorn SC. SGLT2-inhibitor and DPP-4 inhibitor improve brain function via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in HFD-induced obese rats. Toxicol Appl Pharmacol 2017; 333: 43-50 [PMID: 28807765 DOI: 10.1016/j.taap.2017.08.005]Millar P, Pathak N, Parthsarathy V, Bjourson AJ, O'Kane M, Pathak V, Moffett RC, Flatt PR, Gault VA. Metabolic and neuroprotective effects of dapagliflozin and liraglutide in diabetic mice. J Endocrinol 2017; 234: 255-267 [PMID: 28611211 DOI: 10.1530/JOE-17-0263]Lin B, Koibuchi N, Hasegawa Y, Sueta D, Toyama K, Uekawa K, Ma M, Nakagawa T, Kusaka H, Kim-Mitsuyama S. Glycemic control with empagliflozin, a novel selective SGLT2 inhibitor, ameliorates cardiovascular injury and cognitive dysfunction in obese and type 2 diabetic mice. Cardiovasc Diabetol 2014; 13: 148 [PMID: 25344694 DOI: 10.1186/s12933-014-0148-1]Hierro-Bujalance C, Infante-Garcia C, Del Marco A, Herrera M, Carranza-Naval MJ, Suarez J, Alves-Martinez P, Lubian-Lopez S, Garcia-Alloza M. Empagliflozin reduces vascular damage and cognitive impairment in a mixed murine model of Alzheimer's disease and type 2 diabetes. Alzheimers Res Ther 2020; 12: 40 [PMID: 32264944 DOI: 10.1186/s13195-020-00607-4]Wium-Andersen IK, Osler M, Jørgensen MB, Rungby J, Wium-Andersen MK. Antidiabetic medication and risk of dementia in patients with type 2 diabetes: a nested case-control study. Eur J Endocrinol 2019; 181: 499-507 [PMID: 31437816 DOI: 10.1530/EJE-19-0259]Burns J. Dapagliflozin In Alzheimer's Disease. [accessed 2021 Mar 14]. In: ClinicalTrials.gov [Internet]. Kansas City (KS): U.S. National Library of Medicine. Available from: https://clinicaltrials.gov/ct2/show/NCT03801642 ClinicalTrials.gov Identifier: NCT03801642Dhananjayan K, Forbes J, Münch G. Advanced Glycation, Diabetes, and Dementia. In: Srikanth V, Arvanitakis Z. Type 2 Diabetes and Dementia. Elsevier, 2018: 169-193Burstein AH, Sabbagh M, Andrews R, Valcarce C, Dunn I, Altstiel L. Development of Azeliragon, an Oral Small Molecule Antagonist of the Receptor for Advanced Glycation Endproducts, for the Potential Slowing of Loss of Cognition in Mild Alzheimer's Disease. J Prev Alzheimers Dis 2018; 5: 149-154 [PMID: 29616709 DOI: 10.14283/jpad.2018.18]vTv Therapeutics. Study of Azeliragon in Patients With Mild Alzheimer's Disease and Impaired Glucose Tolerance (Elevage). [accessed 2020 Dec 19]. In: ClinicalTrials.gov [Internet]. Tucson (AZ): U.S. National Library of Medicine. Available from: https://clinicaltrials.gov/ct2/show/NCT03980730 ClinicalTrials.gov Identifier: NCT03980730Adler BL, Yarchoan M, Hwang HM, Louneva N, Blair JA, Palm R, Smith MA, Lee HG, Arnold SE, Casadesus G. Neuroprotective effects of the amylin analogue pramlintide on Alzheimer's disease pathogenesis and cognition. Neurobiol Aging 2014; 35: 793-801 [PMID: 24239383 DOI: 10.1016/j.neurobiolaging.2013.10.076]De La Cruz Vargas JA, Dos Santos F, Dyzinger W, Herzog S. Medicina del Estilo de Vida: trabajando juntos para revertir la epidemia de las enfermedades crónicas en Latinoamérica. Cienc E Innov En Salud 2017; 4: 1-7 [DOI: 10.17081/innosa.4.2.2870]Bermudez V, Bermudez F, Arraiz N, Leal E, Linares S, Mengual E, Valdelamar L, Seyfi H, Amell A, Carrillo M, Silva C. Biología molecular de los transportadores de glucosa: clasificación, estructura y distribución. Arch Venez Farmacol Ter 2007; 26: 76-86Vanegas H. Buscando las bases moleculares de la enfermedad de Alzheimer. 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