Pathological and cognitive changes in patients with type 2 diabetes mellitus and comorbid MCI and protective hypoglycemic therapies: a narrative review

References

Abbatecola, A.M., Lattanzio, F., Molinari, A.M., Cioffi, M., Mansi, L., Rambaldi, P., Dicioccio, L., Cacciapuoti, F., Canonico, R., and Paolisso, G. (2010). Rosiglitazone and cognitive stability in older individuals with type 2 diabetes and mild cognitive impairment. Diabetes Care 33, 1706–1711.10.2337/dc09-2030Search in Google Scholar

Alvarenga, K.D.F., Duarte, J.L., Silva, D.P.C.D., Agostinho-Pesse, R.S., Negrato, C.A., and Costa, O.A. (2005). Cognitive P300 potential in subjects with diabetes mellitus. Braz. J. Otorhinolaryngol. 71, 202–207.10.1016/S1808-8694(15)31311-2Search in Google Scholar

American Psychiatric Association (APA) (2013). Diagnostic and statistical manual of mental disorders: DSM-5™ (5th ed.). Codas 25, 275–277.Search in Google Scholar

Araki, Y., Nomura, M., Tanaka, H., Yamamoto, H., Yamamoto, T., Tsukaguchi, I., and Nakamura, H. (1994). MRI of the brain in diabetes mellitus. Neuroradiology 36, 101–103.10.1007/BF00588069Search in Google Scholar PubMed

Arevalo-Rodriguez, I., Smailagic, N., Roque, I.F.M., Ciapponi, A., Sanchez-Perez, E., Giannakou, A., Pedraza, O.L., Bonfill Cosp, X., and Cullum, S. (2015). Mini-Mental State Examination (MMSE) for the detection of Alzheimer’s disease and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst. Rev. 5, Cd010783.10.1002/14651858.CD010783Search in Google Scholar

Bailey, C.J. and Turner, R.C. (1996). Metformin. N. Engl. J. Med. 334, 574–579.10.1056/NEJM199602293340906Search in Google Scholar PubMed

Beeri, M.S., Ravona-Springer, R., Schmeidler, J., Katsel, P., Silverman, J., and Haroutunian, V. (2012). Diabetes characteristics and cognitive compromise: implications for non-diabetic individuals. Alzheimers Dement. 8, 254.10.1016/j.jalz.2012.05.679Search in Google Scholar

Bekinschtein, P., Cammarota, M., Izquierdo, I., and Medina, J.H. (2008). BDNF and memory formation and storage. Neuroscientist 14, 147–156.10.1177/1073858407305850Search in Google Scholar PubMed

Ben Assayag, E., Eldor, R., Korczyn, A.D., Kliper, E., Shenhar-Tsarfaty, S., Tene, O., Molad, J., Shapira, I., Berliner, S., Volfson, V., et al. (2017). Type 2 diabetes mellitus and impaired renal function are associated with brain alterations and poststroke cognitive decline. Stroke 48, 2368–2374.10.1161/STROKEAHA.117.017709Search in Google Scholar PubMed

Benedict, C., Hallschmid, M., Hatke, A., Schultes, B., Fehm, H.L., Born, J., and Kern, W. (2004). Intranasal insulin improves memory in humans. Psychoneuroendocrino. 29, 1326–1334.10.1016/j.psyneuen.2004.04.003Search in Google Scholar PubMed

Bhutada, P., Mundhada, Y., Bansod, K., Tawari, S., Patil, S., Dixit, P., Umathe, S., and Mundhada, D. (2011). Protection of cholinergic and antioxidant system contributes to the effect of berberine ameliorating memory dysfunction in rat model of streptozotocin-induced diabetes. Behav. Brain. Res. 220, 30–41.10.1016/j.bbr.2011.01.022Search in Google Scholar PubMed

Biessels, G.J., Deary, I.J., and Ryan, C.M. (2008). Cognition and diabetes: a lifespan perspective. Lancet. Neurol. 7, 184.10.1016/S1474-4422(08)70021-8Search in Google Scholar

Bohringer, A., Schwabe, L., Richter, S., and Schachinger, H. (2008). Intranasal insulin attenuates the hypothalamic-pituitary-adrenal axis response to psychosocial stress. Psychoneuroendocrino. 33, 1394–1400.10.1016/j.psyneuen.2008.08.002Search in Google Scholar PubMed

Bomfim, T.R., Forny-Germano, L., Sathler, L.B., Brito-Moreira, J., Houzel, J.C., Decker, H., Silverman, M.A., Kazi, H., Melo, H.M., and Mcclean, P.L. (2012). An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer’s disease-associated Aβ oligomers. J. Clin. Invest. 122, 1339–1353.10.1172/JCI57256Search in Google Scholar PubMed PubMed Central

Brownlee, M. (2001). Biochemistry and molecular cell biology of diabetic complications. Nature 414, 813–820.10.1038/414813aSearch in Google Scholar PubMed

Brundel, M., Kappelle, L.J., and Biessels, G.J. (2014). Brain imaging in type 2 diabetes. Eur. Neuropsychopharmacol. 24, 1967–1981.10.1016/j.euroneuro.2014.01.023Search in Google Scholar PubMed

Cai, R., Han, J., Sun, J., Huang, R., Tian, S., Shen, Y., and Wang, S. (2017). Effects of ABCA1 R219K polymorphism and serum lipid profiles on mild cognitive impairment in type 2 diabetes mellitus. Front. Aging. Neurosci. 9, 257.10.3389/fnagi.2017.00257Search in Google Scholar PubMed PubMed Central

Calon, F., Lim, G.P., Yang, F., Morihara, T., Teter, B., Ubeda, O., Rostaing, P., Triller, A., Salem Jr. N., Ashe, K.H., et al. (2004). Docosahexaenoic acid protects from dendritic pathology in an Alzheimer’s disease mouse model. Neuron 43, 633–645.10.1016/j.neuron.2004.08.013Search in Google Scholar PubMed PubMed Central

Chan, A. and Shea, T.B. (2007). Folate deprivation increases presenilin expression, gamma-secretase activity, and Abeta levels in murine brain: potentiation by ApoE deficiency and alleviation by dietary S-adenosyl methionine. J. Neurochem. 102, 753–760.10.1111/j.1471-4159.2007.04589.xSearch in Google Scholar PubMed

Chen, R.H., Jiang, X.Z., Zhao, X.H., Qin, Y.L., Gu, Z., Gu, P.L., Zhou, B., Zhu, Z.H., Xu, L.Y., and Zou, Y.F. (2012). Risk factors of mild cognitive impairment in middle aged patients with type 2 diabetes: a cross-section study. Ann. Endocrinol. (Paris) 73, 208–212.10.1016/j.ando.2012.04.009Search in Google Scholar PubMed

Chiu, S.L., Chen, C.M., and Cline, H.T. (2008). Insulin receptor signaling regulates synapse number, dendritic plasticity, and circuit function in vivo. Neuron. 58, 708–719.10.1016/j.neuron.2008.04.014Search in Google Scholar PubMed PubMed Central

Chris, M., Phan, T.G., Jian, C., Leigh, B., Richard, B., Alison, V., Gerald, M., Wood, A.G., Josephine, F., and Greenaway, T.M. (2013). Brain atrophy in type 2 diabetes: regional distribution and influence on cognition. Diabetes Care 36, 4036–4042.10.2337/dc13-0143Search in Google Scholar

Claxton, A., Baker, L.D., Wilkinson, C.W., Trittschuh, E.H., Chapman, D., Watson, G.S., Cholerton, B., Plymate, S.R., Arbuckle, M., and Craft, S. (2013). Sex and ApoE genotype differences in treatment response to two doses of intranasal insulin in adults with mild cognitive impairment or Alzheimer’s disease. J. Alzheimers Dis. 35, 789–797.10.3233/JAD-122308Search in Google Scholar

Conrad, C.D., Mclaughlin, K.J., Harman, J.S., Foltz, C., Wieczorek, L., Lightner, E., and Wright, R.L. (2007). Chronic glucocorticoids increase hippocampal vulnerability to neurotoxicity under conditions that produce CA3 dendritic retraction but fail to impair spatial recognition memory. J. Neurosci. 27, 8278–8285.10.1523/JNEUROSCI.2121-07.2007Search in Google Scholar

Craft, S., Asthana, S., Cook, D.G., Baker, L.D., Cherrier, M., Purganan, K., Wait, C., Petrova, A., Latendresse, S., Watson, G.S., et al. (2003). Insulin dose-response effects on memory and plasma amyloid precursor protein in Alzheimer’s disease: interactions with apolipoprotein E genotype. Psychoneuroendocrino. 28, 809–822.10.1016/S0306-4530(02)00087-2Search in Google Scholar

Craft, S., Baker, L.D., Montine, T.J., Minoshima, S., Watson, G.S., Claxton, A., Arbuckle, M., Callaghan, M., Tsai, E., Plymate, S.R., et al. (2012). Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch. Neurol. 69, 29–38.10.1001/archneurol.2011.233Search in Google Scholar PubMed PubMed Central

Crowe, T.P., Greenlee, M.H.W., Kanthasamy, A.G., and Hsu, W.H. (2018). Mechanism of intranasal drug delivery directly to the brain. Life Sci. 195, 44–52.10.1016/j.lfs.2017.12.025Search in Google Scholar PubMed

Cui, Y., Jiao, Y., Chen, Y.C., Wang, K., Gao, B., Wen, S., Ju, S., and Teng, G.J. (2014). Altered spontaneous brain activity in type 2 diabetes: a resting-state functional MRI study. Diabetes 63, 749–760.10.2337/db13-0519Search in Google Scholar PubMed

Cukierman, T., Gerstein, H.C., and Williamson, J.D. (2005). Cognitive decline and dementia in diabetes – systematic overview of prospective observational studies. Diabetologia 48, 2460–2469.10.1007/s00125-005-0023-4Search in Google Scholar PubMed

Dai, J., Jones, D.P., Goldberg, J., Ziegler, T.R., Bostick, R.M., Wilson, P.W., Manatunga, A.K., Shallenberger, L., Jones, L., and Vaccarino, V. (2008). Association between adherence to the Mediterranean diet and oxidative stress. Am. J. Clin. Nutr. 88, 1364–1370.Search in Google Scholar

Dandona, P. (2002). Endothelium, inflammation, and diabetes. Curr. Diab. Rep. 2, 311–315.10.1007/s11892-002-0019-0Search in Google Scholar PubMed

Dauwels, J., Vialatte, F., and Cichocki, A. (2010). Diagnosis of Alzheimer’s disease from EEG signals: where are we standing. Curr. Alzheimer Res. 7, 487–505.10.2174/1567210204558652050Search in Google Scholar

Den, H.T., Vermeer, S.E., Van Dijk, E.J., Prins, N.D., Koudstaal, P.J., Hofman, A., and Breteler, M.M. (2003). Type 2 diabetes and atrophy of medial temporal lobe structures on brain MRI. Diabetologia 46, 1604–1610.10.1007/s00125-003-1235-0Search in Google Scholar

Espeland, M.A., Nick, B.R., Goveas, J.S., Robinson, J.G., Siddiqui, M.S., Liu, S., Hogan, P.E., Ramon, C., Coker, L.H., and Kristine, Y. (2013). Influence of type 2 diabetes on brain volumes and changes in brain volumes. Diabetes Care 36, 90–97.10.2337/dc12-0555Search in Google Scholar

Falk, T.H., Fraga, F.J., Trambaiolli, L., and Anghinah, R. (2012). Erratum to: EEG amplitude modulation analysis for semi-automated diagnosis of Alzheimer’s disease. Eurasip. J. Adv. Sig. Pr. 2012, 192–200.10.1186/1687-6180-2014-49Search in Google Scholar

Falvey, C.M., Rosano, C., Simonsick, E.M., Harris, T., Strotmeyer, E.S., Satterfield, S., and Yaffe, K. (2013). Macro- and microstructural magnetic resonance imaging indices associated with diabetes among community-dwelling older adults. Diabetes Care 36, 677–682.10.2337/dc12-0814Search in Google Scholar

Féart, C., Samieri, C., Rondeau, V., Amieva, H., Portet, F., Dartigues, J.F., Scarmeas, N., and Barbergergateau, P. (2009). Adherence to a Mediterranean diet, cognitive decline, and risk of dementia. J. Am. Med. Assoc. 302, 638–648.10.1001/jama.2009.1146Search in Google Scholar

Foley, D.J. and White, L.R. (2002). Dietary intake of antioxidants and risk of Alzheimer disease: food for thought. J. Am. Med. Assoc. 287, 3261–3263.10.1001/jama.287.24.3261Search in Google Scholar

Garcion, E., Wionbarbot, N., Monteromenei, C.N., Berger, F., and Wion, D. (2002). New clues about vitamin D functions in the nervous system. Trends. Endocrinol. Metab. 13, 100–105.10.1016/S1043-2760(01)00547-1Search in Google Scholar

Gillette Guyonnet, S., Abellan Van Kan, G., Andrieu, S., Barberger Gateau, P., Berr, C., Bonnefoy, M., Dartigues, J.F., De Groot, L., Ferry, M., Galan, P., et al. (2007). IANA task force on nutrition and cognitive decline with aging. J. Nutr. Health. Aging 11, 132–152.Search in Google Scholar

Gregg, E.W., Yaffe, K., Cauley, J.A., Rolka, D.B., Blackwell, T.L., Narayan, K.M.V., and Cummings, S.R. (2000). Is diabetes associated with cognitive impairment and cognitive decline among older women? Study of Osteoporotic Fractures Research Group. Arch. Intern. Med. 160, 174–180.10.1001/archinte.160.2.174Search in Google Scholar PubMed

Grodstein, F., Chen, J., Wilson, R.S., and Manson, J.A.E. (2001). Type 2 diabetes and cognitive function in community-dwelling elderly women. Diabetes Care 24, 1060–1065.10.2337/diacare.24.6.1060Search in Google Scholar PubMed

Guo, M., Mi, J., Jiang, Q.M., Xu, J.M., Tang, Y.Y., Tian, G., and Wang, B. (2014). Metformin may produce antidepressant effects through improvement of cognitive function among depressed patients with diabetes mellitus. Clin. Exp. Pharmacol. Physiol. 41, 650–656.10.1111/1440-1681.12265Search in Google Scholar PubMed

Hampel, H., Lista, S., Teipel, S.J., Garaci, F., Nistico, R., Blennow, K., Zetterberg, H., Bertram, L., Duyckaerts, C., Bakardjian, H., et al. (2014). Perspective on future role of biological markers in clinical therapy trials of Alzheimer’s disease: a long-range point of view beyond 2020. Biochem. Pharmacol. 88, 426–449.10.1016/j.bcp.2013.11.009Search in Google Scholar PubMed

Hanyu, H., Sato, T., Kiuchi, A., Sakurai, H., and Iwamoto, T. (2009). Pioglitazone improved cognition in a pilot study on patients with Alzheimer’s disease and mild cognitive impairment with diabetes mellitus. J. Am. Geriatr. Soc. 57, 177–179.10.1111/j.1532-5415.2009.02067.xSearch in Google Scholar PubMed

Hardigan, T., Ward, R., and Ergul, A. (2016). Cerebrovascular complications of diabetes: focus on cognitive dysfunction. Clin. Sci. (Lond.) 130, 1807–1822.10.1042/CS20160397Search in Google Scholar PubMed PubMed Central

Harrington, C., Sawchak, S., Chiang, C., Davies, J., Donovan, C., Saunders, A.M., Irizarry, M., Jeter, B., Zvartauhind, M., and Van Dyck, C.H. (2011). Rosiglitazone does not improve cognition or global function when used as adjunctive therapy to AChE inhibitors in mild-to-moderate Alzheimer’s disease: two phase 3 studies. Curr. Alzheimer. Res. 8, 592–606.10.2174/156720511796391935Search in Google Scholar PubMed

Holscher, C. (2010). Incretin analogues that have been developed to treat type 2 diabetes hold promise as a novel treatment strategy for Alzheimer’s disease. Recent. Pat. CNS Drug Discov. 5, 109–117.10.2174/157488910791213130Search in Google Scholar PubMed

Hölscher, C. and Li, L. (2010). New roles for insulin-like hormones in neuronal signalling and protection: new hopes for novel treatments of Alzheimer’s disease. Neurobiol. Aging 31, 1495–1502.10.1016/j.neurobiolaging.2008.08.023Search in Google Scholar PubMed

Hong, M. and Lee, V.M. (1997). Insulin and insulin-like growth factor-1 regulate tau phosphorylation in cultured human neurons. J. Biol. Chem. 272, 19547–19553.10.1074/jbc.272.31.19547Search in Google Scholar PubMed

Hoogenboom, W.S., Marder, T.J., Flores, V.L., Huisman, S., Eaton, H.P., Schneiderman, J.S., Bolo, N.R., Simonson, D.C., Jacobson, A.M., and Kubicki, M. (2014). Cerebral white matter integrity and resting-state functional connectivity in middle-aged patients with type 2 diabetes. Diabetes 63, 728–738.10.2337/db13-1219Search in Google Scholar PubMed PubMed Central

Hou, R.C., Chen, H.L., Tzen, J.T., and Jeng, K.C. (2003). Effect of sesame antioxidants on LPS-induced NO production by BV2 microglial cells. Neuroreport 14, 1815–1819.10.1097/00001756-200310060-00011Search in Google Scholar PubMed

Imfeld, P., Bodmer, M., Jick, S.S., and Meier, C.R. (2012). Metformin, other antidiabetic drugs, and risk of Alzheimer’s disease: a population-based case-control study. J. Am. Geriatr. Soc. 60, 916–921.10.1111/j.1532-5415.2012.03916.xSearch in Google Scholar PubMed

Jalsrai, A., Numakawa, T., Ooshima, Y., Adachi, N., and Kunugi, H. (2014). Phosphatase-mediated intracellular signaling contributes to neuroprotection by flavonoids of Iris tenuifolia. Am. J. Chin. Med. 42, 119–130.10.1142/S0192415X14500086Search in Google Scholar PubMed

Jasper, H. (1958). The 10–20 electrode system of the International Federation. Eeg. Clin. Neurophysiol. 10, 370–375.Search in Google Scholar

Jeong, J. (2004). EEG dynamics in patients with Alzheimer’s disease. Clin. Neurophysiol. 115, 1490–1505.10.1016/j.clinph.2004.01.001Search in Google Scholar PubMed

Jeroen, D.B., Tiehuis, A.M., Esther, V.D.B., Reijmer, Y.D., Cynthia, J., Jaap, K.L., Mali, W.P., Viergever, M.A., and Jan, B.G. (2010). Progression of cerebral atrophy and white matter hyperintensities in patients with type 2 diabetes. Diabetes Care 33, 1309–1314.10.2337/dc09-1923Search in Google Scholar PubMed PubMed Central

Jiang, Q.A.B. (2003). Gamma-Tocopherol, but not alpha-tocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats. FASEB J. 17, 816–822.10.1096/fj.02-0877comSearch in Google Scholar PubMed

Jiang, Q., Heneka, M., and Landreth, G.E. (2008). The role of peroxisome proliferator-activated receptor-γ (PPARγ) in Alzheimer’s disease: therapeutic implications. CNS Drugs 22, 1–14.10.2165/00023210-200822010-00001Search in Google Scholar PubMed

Jongen, C., Van, D.G.J., Kappelle, L.J., Biessels, G.J., Viergever, M.A., and Pluim, J.P. (2007). Automated measurement of brain and white matter lesion volume in type 2 diabetes mellitus. Diabetologia 50, 1509–1516.10.1007/s00125-007-0688-ySearch in Google Scholar PubMed PubMed Central

Kalmijn, S., Feskens, E.J.M., Launer, L.J., Stijnen, T., and Kromhout, D. (1995). Glucose intolerance, hyperinsulinaemia and cognitive function in a general population of elderly men. Diabetologia 38, 1096–1102.10.1007/BF00402181Search in Google Scholar PubMed

Kanaya, A.M., Barrettconnor, E., Gildengorin, G., and Yaffe, K. (2004). Change in cognitive function by glucose tolerance status in older adults: a 4-year prospective study of the Rancho Bernardo study cohort. Arch. Intern. Med. 164, 1327–1333.10.1001/archinte.164.12.1327Search in Google Scholar PubMed

Katayama, S., Ogawa, H., and Nakamura, S. (2011). Apricot carotenoids possess potent anti-amyloidogenic activity in vitro. J. Agric. Food. Chem. 59, 12691–12696.10.1021/jf203654cSearch in Google Scholar PubMed

Kivipelto, M., Ngandu, T., Fratiglioni, L., Viitanen, M., Kareholt, I., Winblad, B., Helkala, E.L., Tuomilehto, J., Soininen, H., and Nissinen, A. (2005). Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch. Neurol. 62, 1556–1560.10.1001/archneur.62.10.1556Search in Google Scholar PubMed

Knopman, D.S., Mosley, T.H., Catellier, D.J., and Sharrett, A.R. (2005). Cardiovascular risk factors and cerebral atrophy in a middle-aged cohort. Neurology 65, 876–881.10.1212/01.wnl.0000176074.09733.a8Search in Google Scholar

Knopman, D.S., Penman, A.D., Catellier, D.J., Coker, L.H., Shibata, D.K., Sharrett, A.R., and Mosley Jr. T.H. (2011). Vascular risk factors and longitudinal changes on brain MRI: the ARIC study. Neurology 76, 1879–1885.10.1212/WNL.0b013e31821d753fSearch in Google Scholar

Kong, L.Y., Shing, K.C., and Sonal, S. (2011). Comparative cardiovascular effects of thiazolidinediones: systematic review and meta-analysis of observational studies. Br. Med. J. 342, d1309.10.1136/bmj.d1309Search in Google Scholar

Kooistra, M., Geerlings, M.I., Mali, W.P.T.M., Vincken, K.L., Graaf, Y.V.D., and Biessels, G.J. (2013). Diabetes mellitus and progression of vascular brain lesions and brain atrophy in patients with symptomatic atherosclerotic disease. The SMART-MR study. J. Neurol. Sci. 332, 69–74.10.1016/j.jns.2013.06.019Search in Google Scholar

Korf, E.S., Scheltens, P., and Launer, L.J. (2006). Brain aging in very old men with type 2 diabetes: the Honolulu-Asia Aging Study. Diabetes Care 29, 2268–2274.10.2337/dc06-0243Search in Google Scholar

Kowalski, J., Pl, M.E., Gawel, M., Pfeffer, A., and Barcikowska, M. (2001). The diagnostic value of EEG in Alzheimer disease: correlation with the severity of mental impairment. J. Clin. Neurophysiol. 18, 570–575.10.1097/00004691-200111000-00008Search in Google Scholar

Kravitz, E., Schmeidler, J., and Schnaider, B.M. (2013). Type 2 diabetes and cognitive compromise: potential roles of diabetes-related therapies. Endocrinol. Metab. Clin. North Am. 42, 489–501.10.1016/j.ecl.2013.05.009Search in Google Scholar

Kurochkin, I.V., Guarnera, E., and Berezovsky, I.N. (2017). Insulin-degrading enzyme in the fight against Alzheimer’s disease. Trends. Pharmacol. Sci. 39, 49–58.10.1016/j.tips.2017.10.008Search in Google Scholar

Łabuzek, K., Suchy, D., Gabryel, B., Bielecka, A., Liber, S., and Okopień, B. (2010). Quantification of metformin by the HPLC method in brain regions, cerebrospinal fluid and plasma of rats treated with lipopolysaccharide. Pharmacol Rep. 62, 956–965.10.1016/S1734-1140(10)70357-1Search in Google Scholar

Last, D., Bazelaire, C.D., Alsop, D.C., Hu, K., Abduljalil, A.M., Cavallerano, J., Marquis, R.P., and Novak, V. (2007). Global and regional effects of type 2 diabetes on brain tissue volumes and cerebral vasoreactivity. Diabetes Care. 30, 1193–1199.10.2337/dc06-2052Search in Google Scholar PubMed PubMed Central

Lee, Z.S., Chan, J.C., Yeung, V.T., Chow, C.C., Lau, M.S., Ko, G.T., Li, J.K., Cockram, C.S., and Critchley, J.A. (1999). Plasma insulin, growth hormone, cortisol, and central obesity among young Chinese type 2 diabetic patients. Diabetes Care 22, 1450–1457.10.2337/diacare.22.9.1450Search in Google Scholar PubMed

Lerche, S., Brock, B., Rungby, J., Bøtker, H.E., Møller, N., Rodell, A., Bibby, B.M., Holst, J.J., Schmitz, O., and Gjedde, A. (2008). Glucagon-like peptide-1 inhibits blood-brain glucose transfer in humans. Diabetes 57, 325–331.10.2337/db07-1162Search in Google Scholar PubMed

Letenneur, L., Larrieu, S., and Barberger-Gateau, P. (2004). Alcohol and tobacco consumption as risk factors of dementia: a review of epidemiological studies. Biomed. Pharmacother. 58, 95–99.10.1016/j.biopha.2003.12.004Search in Google Scholar PubMed

Leys, D. and Pasquier, F. (1999). [Arterial hypertension and cognitive decline]. Rev. Neurol. (Paris) 155, 743–748.Search in Google Scholar

Li, L. (2007). Is Glucagon-like peptide-1, an agent treating diabetes, a new hope for Alzheimer’s disease. Neurosci. Bull. 23, 58–65.10.1007/s12264-007-0009-ySearch in Google Scholar PubMed PubMed Central

Li, J., Deng, J., Sheng, W., and Zuo, Z. (2012). Metformin attenuates Alzheimer’s disease-like neuropathology in obese, leptin-resistant mice. Pharmacol. Biochem. Behav. 101, 564–574.10.1016/j.pbb.2012.03.002Search in Google Scholar PubMed PubMed Central

Li, W., Risacher, S.L., Huang, E., and Saykin, A.J. (2016). Type 2 diabetes mellitus is associated with brain atrophy and hypometabolism in the ADNI cohort. Neurology 87, 595–600.10.1212/WNL.0000000000002950Search in Google Scholar PubMed PubMed Central

Lim, G.P., Calon, F., Morihara, T., Yang, F., Teter, B., Ubeda, O., Salem Jr. N., Frautschy, S.A., and Cole, G.M. (2005). A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J. Neurosci. 25, 3032–3040.10.1523/JNEUROSCI.4225-04.2005Search in Google Scholar PubMed PubMed Central

Lin, Y., Zhou, J., Sha, L., Li, Y., Qu, X., Liu, L., Chen, H., An, Z., Wang, Y., and Sun, C. (2013). Metabolite differences in the lenticular nucleus in type 2 diabetes mellitus shown by proton MR spectroscopy. AJNR. Am. J. Neuroradiol. 34, 1692–1696.10.3174/ajnr.A3492Search in Google Scholar PubMed PubMed Central

Ling, J., Cheng, P., Ge, L., Zhang, D.H., Shi, A.C., Tian, J.H., Chen, Y.J., Li, X.X., Zhang, J.Y., and Yang, K.H. (2019). The efficacy and safety of dipeptidyl peptidase-4 inhibitors for type 2 diabetes: a Bayesian network meta-analysis of 58 randomized controlled trials. Acta Diabetol. 56, 249–272.10.1007/s00592-018-1222-zSearch in Google Scholar PubMed

Logroscino, G., Kang, J.H., and Grodstein, F. (2004). Prospective study of type 2 diabetes and cognitive decline in women aged 70–81 years. Br. Med. J. 328, 548–551.10.1136/bmj.37977.495729.EESearch in Google Scholar PubMed PubMed Central

Lommatzsch, M., Zingler, D., Schuhbaeck, K., Schloetcke, K., Zingler, C., Schuffwerner, P., and Virchow, J.C. (2005). The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiol. Aging 26, 115–123.10.1016/j.neurobiolaging.2004.03.002Search in Google Scholar

Luchsinger, J.A., Tang, M.X., Siddiqui, M., Steven Shea, M.D., and Richard Mayeux, M.D. (2004). Alcohol intake and risk of dementia. J. Am. Geriatr. Soc. 52, 540–546.10.1111/j.1532-5415.2004.52159.xSearch in Google Scholar

Lupien, S., Lecours, A.R., Lussier, I., Schwartz, G., Nair, N.P., and Meaney, M.J. (1994). Basal cortisol levels and cognitive deficits in human aging. J. Neurosci. 14, 2893–2903.10.1523/JNEUROSCI.14-05-02893.1994Search in Google Scholar

Mannucci, E., Monami, M., Bari, M.D., Lamanna, C., Gori, F., Gensini, G.F., and Marchionni, N. (2010). Cardiac safety profile of rosiglitazone: A comprehensive meta-analysis of randomized clinical trials. Int. J. Cardiol. 143, 135–140.10.1016/j.ijcard.2009.01.064Search in Google Scholar

Matsuzaki, T., Sasaki, K., Tanizaki, Y., Hata, J., Fujimi, K., Matsui, Y., Sekita, A., Suzuki, S.O., Kanba, S., and Kiyohara, Y. (2010). Insulin resistance is associated with the pathology of Alzheimer disease: the Hisayama study. Neurology 75, 764–770.10.1212/WNL.0b013e3181eee25fSearch in Google Scholar

Mccarty, M.F. (2006). Toward prevention of Alzheimers disease – potential nutraceutical strategies for suppressing the production of amyloid b peptides. Med. Hypotheses 67, 682–697.10.1016/j.mehy.2006.04.067Search in Google Scholar

Mcclean, P.L., Gault, V.A., Harriott, P., and Hölscher, C. (2010). Glucagon-like peptide-1 analogues enhance synaptic plasticity in the brain: a link between diabetes and Alzheimer’s disease. Eur. J. Pharmacol. 630, 158–162.10.1016/j.ejphar.2009.12.023Search in Google Scholar

Mccrimmon, R.J., Ryan, C.M., and Frier, B.M. (2012). Diabetes and cognitive dysfunction. Lancet 379, 2291–2299.10.1016/S0140-6736(12)60360-2Search in Google Scholar

Mcdowell, K., Kerick, S.E., Maria, D.L.S., and Hatfield, B.D. (2003). Aging, physical activity, and cognitive processing: an examination of P300. Neurobiol. Aging 24, 597–606.10.1016/S0197-4580(02)00131-8Search in Google Scholar

Mckhann, G.M., Knopman, D.S., Chertkow, H., Hyman, B.T., Jack, C.R., Jr., Kawas, C.H., Klunk, W.E., Koroshetz, W.J., Manly, J.J., Mayeux, R., et al. (2011). The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 7, 263–269.10.1016/j.jalz.2011.03.005Search in Google Scholar PubMed PubMed Central

Mcnay, E.C. and Recknagel, A.K. (2011). Brain insulin signaling: a key component of cognitive processes and a potential basis for cognitive impairment in type 2 diabetes. Neurobiol. Learn. Mem. 96, 432–442.10.1016/j.nlm.2011.08.005Search in Google Scholar PubMed PubMed Central

Middleton, L.E., Manini, T.M., Simonsick, E.M., Harris, T.B., Barnes, D.E., Tylavsky, F., Brach, J.S., Everhart, J.E., and Yaffe, K. (2011). Activity energy expenditure and incident cognitive impairment in older adults. Arch. Intern. Med. 171, 1251–1257.10.1001/archinternmed.2011.277Search in Google Scholar PubMed PubMed Central

Moore, E.M., Mander, A.G., Ames, D., Kotowicz, M.A., Carne, R.P., Brodaty, H., Woodward, M., Boundy, K., Ellis, K.A., and Bush, A.I. (2014). Increased risk of cognitive impairment in patients with diabetes is associated with metformin. Diabetes Care 37, e151.10.2337/dc13-0229Search in Google Scholar PubMed PubMed Central

Moran, C., Phan, T.G., Chen, J., Blizzard, L., Beare, R., Venn, A., Münch, G., Wood, A.G., Forbes, J., and Greenaway, T.M. (2013). Brain Atrophy in Type 2 Diabetes: regional distribution and influence on cognition. Diabetes Care 36, 4036–4042.10.2337/dc13-0143Search in Google Scholar PubMed PubMed Central

Morris, M.C. (2012). Nutritional determinants of cognitive aging and dementia. Proc. Nutr. Soc. 71, 1–13.10.1017/S0029665111003296Search in Google Scholar PubMed

Morris, M.C. and Tangney, C.C. (2014). Dietary fat composition and dementia risk. Neurobiol Aging. 35, S59–S64.10.1016/j.neurobiolaging.2014.03.038Search in Google Scholar PubMed PubMed Central

Morris, M.C., Evans, D.A., Bienias, J.L., Tangney, C.C., Bennett, D.A., Wilson, R.S., Aggarwal, N., and Schneider, J. (2003). Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch. Neurol. 60, 940–946.10.1001/archneur.60.7.940Search in Google Scholar PubMed

Morrison, C., Rabipour, S., Taler, V., Sheppard, C., and Knoefel, F. (2019). Visual event-related potentials in mild cognitive impairment and Alzheimer’s disease: a literature review. Curr. Alzheimer. Res. 16, 67–89.10.2174/1567205015666181022101036Search in Google Scholar PubMed

Mossello, E., Ballini, E., Boncinelli, M., Monami, M., Lonetto, G., Mello, A.M., Tarantini, F., Baldasseroni, S., Mannucci, E., and Marchionni, N. (2011). Glucagon-like peptide-1, diabetes, and cognitive decline: possible pathophysiological links and therapeutic opportunities. Exp. Diabetes. Res. 2011, 281674.10.1155/2011/281674Search in Google Scholar PubMed PubMed Central

Nasreddine, Z.S., Phillips, N.A., Bédirian, V., Charbonneau, S., Whitehead, V., Collin, I., Cummings, J.L., and Chertkow, H. (2010). The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J. Am. Geriatr. Soc. 53, 695–699.10.1111/j.1532-5415.2005.53221.xSearch in Google Scholar PubMed

Nishida, Y., Ito, S., Ohtsuki, S., Yamamoto, N., Takahashi, T., Iwata, N., Jishage, K., Yamada, H., Sasaguri, H., Yokota, S., et al. (2009). Depletion of vitamin E increases amyloid beta accumulation by decreasing its clearances from brain and blood in a mouse model of Alzheimer disease. J. Biol. Chem. 284, 33400–33408.10.1074/jbc.M109.054056Search in Google Scholar PubMed PubMed Central

Nishimura, S. (2006). Mediterranean diet and risk for Alzheimer’s disease. Ann. Neurol. 59, 912–921.10.1002/ana.20854Search in Google Scholar PubMed PubMed Central

Nissen, S.E. and Wolski, K. (2010). Rosiglitazone revisited: an updated meta-analysis of risk for myocardial infarction and cardiovascular mortality. Arch. Intern. Med. 170, 1191–1201.10.1001/archinternmed.2010.207Search in Google Scholar PubMed

Novak, V. and Hajjar, I. (2010). The relationship between blood pressure and cognitive function. Nat. Rev. Cardiol. 7, 686–698.10.1038/nrcardio.2010.161Search in Google Scholar PubMed PubMed Central

Novak, V., Last, D., Alsop, D.C., Abduljalil, A.M., Hu, K., Lepicovsky, L., Cavallerano, J., and Lipsitz, L.A. (2006). Cerebral blood flow velocity and periventricular white matter hyperintensities in type 2 diabetes. Diabetes Care 29, 1529–1534.10.2337/dc06-0261Search in Google Scholar PubMed PubMed Central

Obulesu, M., Dowlathabad, M.R., and Bramhachari, P.V. (2011). Carotenoids and Alzheimer’s disease: an insight into therapeutic role of retinoids in animal models. Neurochem. Int. 59, 535–541.10.1016/j.neuint.2011.04.004Search in Google Scholar PubMed

Ortíz, B.M., Emiliano, J.R., Ramosrodríguez, E., Martínezgarza, S., Macíascervantes, H., Soloriomeza, S., and Pereyranobara, T.A. (2016). Brain-derived neurotrophic factor plasma levels and premature cognitive impairment/dementia in type 2 diabetes. World J. Diabetes 7, 615–620.10.4239/wjd.v7.i20.615Search in Google Scholar PubMed PubMed Central

Ott, A., Stolk, R.P., Van Harskamp, F., Pols, H.A., Hofman, A., and Breteler, M.M. (1999a). Diabetes mellitus and the risk of dementia: the Rotterdam Study. Neurology 53, 1937–1942.10.1212/WNL.53.9.1937Search in Google Scholar PubMed

Ott, A., Stolk, R.P., Van, H.F., Pols, H.A., Hofman, A., and Breteler, M.M. (1999b). Diabetes mellitus and the risk of dementia: the Rotterdam Study. Neurology 53, 1937–1942.10.1212/WNL.53.9.1937Search in Google Scholar

Palta, P., Schneider, A.L., Biessels, G.J., Touradji, P., and Hill-Briggs, F. (2014). Magnitude of cognitive dysfunction in adults with type 2 diabetes: a meta-analysis of six cognitive domains and the most frequently reported neuropsychological tests within domains. J. Int. Neuropsychol. Soc. 20, 278–291.10.1017/S1355617713001483Search in Google Scholar PubMed PubMed Central

Pathan, A.R., Viswanad, B., Sonkusare, S.K., and Ramarao, P. (2006). Chronic administration of pioglitazone attenuates intracerebroventricular streptozotocin induced-memory impairment in rats. Life. Sci. 79, 2209–2216.10.1016/j.lfs.2006.07.018Search in Google Scholar

Peng, J., Qu, H., Peng, J., Luo, T.Y., Lv, F.J., Chen, L., Wang, Z.N., Ouyang, Y., and Cheng, Q.F. (2016). Abnormal spontaneous brain activity in type 2 diabetes with and without microangiopathy revealed by regional homogeneity. Eur. J. Radiol. 85, 607–615.10.1016/j.ejrad.2015.12.024Search in Google Scholar

Perry, T. and Greig, N.H. (2005). Enhancing central nervous system endogenous GLP-1 receptor pathways for intervention in Alzheimer’s disease. Curr. Alzheimer Res. 2, 377–385.10.2174/1567205054367892Search in Google Scholar

Qin, B., Nagasaki, M., Ren, M., Bajotto, G., Oshida, Y., and Sato, Y. (2003). Cinnamon extract (traditional herb) potentiates in vivo insulin-regulated glucose utilization via enhancing insulin signaling in rats. Diabetes. Res. Clin. Pract. 62, 139–148.10.1016/S0168-8227(03)00173-6Search in Google Scholar

Rabinovitz, H., Friedensohn, A., Leibovitz, A., Gabay, G., Rocas, C., and Habot, B. (2004). Effect of chromium supplementation on blood glucose and lipid levels in type 2 diabetes mellitus elderly patients. Int. J. Vitam. Nutr. Res. 74, 178–182.10.1024/0300-9831.74.3.178Search in Google Scholar PubMed

Rawlings, A.M., Sharrett, A.R., Schneider, A.L.C., Coresh, J., Albert, M., Couper, D., Griswold, M., Gottesman, R.F., Wagenknecht, L.E., and Windham, B.G. (2014). Diabetes in midlife and cognitive change over 20 years: a cohort study. Ann. Intern. Med. 161, 785–793.10.7326/M14-0737Search in Google Scholar PubMed PubMed Central

Reger, M.A., Watson, G.S., Frey, 2nd, W.H., Baker, L.D., Cholerton, B., Keeling, M.L., Belongia, D.A., Fishel, M.A., Plymate, S.R., Schellenberg, G.D., Cherrier, M.M., and Craft, S. (2006). Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype. Neurobiol. Aging 27, 451–458.10.1016/j.neurobiolaging.2005.03.016Search in Google Scholar PubMed

Reger, M.A., Watson, G.S., Green, P.S., Wilkinson, C.W., Baker, L.D., Cholerton, B., Fishel, M.A., Plymate, S.R., Breitner, J.C., Degroodt, W., et al. (2008). Intranasal insulin improves cognition and modulates beta-amyloid in early AD. Neurology 70, 440–448.10.1212/01.WNL.0000265401.62434.36Search in Google Scholar PubMed

Reijmer, Y.D., Leemans, A., Brundel, M., Kappelle, L.J., and Biessels, G.J. (2013). Disruption of the cerebral white matter network is related to slowing of information processing speed in patients with type 2 diabetes. Diabetes 62, 2112–2115.10.2337/db12-1644Search in Google Scholar PubMed PubMed Central

Reske-Nielsen, E. and Lundbaek, K. (1968). Pathological changes in the central and peripheral nervous system of young long-term diabetics. II. The spinal cord and peripheral nerves. Diabetologia 6, 34–43.10.1007/BF01241031Search in Google Scholar PubMed

Risner, M.E., Saunders, A.M., Altman, J.F., Ormandy, G.C., Craft, S., Foley, I.M., Zvartauhind, M.E., Hosford, D.A., and Roses, A.D. (2006). Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer’s disease. Pharmacogenomics. J. 6, 246–254.10.1038/sj.tpj.6500369Search in Google Scholar PubMed

Ryan, C.M., Geckle, M.O., and Orchard, T.J. (2003). Cognitive efficiency declines over time in adults with Type 1 diabetes: effects of micro- and macrovascular complications. Diabetologia 46, 940–948.10.1007/s00125-003-1128-2Search in Google Scholar PubMed

Ryan, J.P., Aizenstein, H.J., Orchard, T.J., Nunley, K.A., Karim, H., and Rosano, C. (2018). Basal ganglia cerebral blood flow associates with psychomotor speed in adults with type 1 diabetes. Brain. Imaging. Behav. 12, 1271–1278.10.1007/s11682-017-9783-ySearch in Google Scholar PubMed PubMed Central

Sabri, O., Hellwig, D., Schreckenberger, M., Schneider, R., Kaiser, H.J., Wagenknecht, G., Mull, M., and Buell, U. (2000). Influence of diabetes mellitus on regional cerebral glucose metabolism and regional cerebral blood flow. Nucl. Med. Commun. 21, 19–29.10.1097/00006231-200001000-00005Search in Google Scholar PubMed

Saczynski, J.S., Jonsdottir, M.K., Garcia, M.E., Jonsson, P.V., Peila, R., Eiriksdottir, G., Olafsdottir, E., Harris, T.B., Gudnason, V., and Launer, L.J. (2008). Cognitive impairment: an increasingly important complication of type 2 diabetes: the age, gene/environment susceptibility – Reykjavik study. Am. J. Epidemiol. 168, 1132–1139.10.1093/aje/kwn228Search in Google Scholar PubMed PubMed Central

Sartorius, A., Hellweg, R., Litzke, J., Vogt, M., Dormann, C., Vollmayr, B., Dankerhopfe, H., and Gass, P. (2009). Correlations and discrepancies between serum and brain tissue levels of neurotrophins after electroconvulsive treatment in rats. Pharmacopsychiatry 42, 270–276.10.1055/s-0029-1224162Search in Google Scholar PubMed

Sato, T., Hanyu, H., Hirao, K., Kanetaka, H., Sakurai, H., and Iwamoto, T. (2011). Efficacy of PPAR-γ agonist pioglitazone in mild Alzheimer disease. Neurobiol. Aging 32, 1626–1633.10.1016/j.neurobiolaging.2009.10.009Search in Google Scholar PubMed

Scarmeas, N., Luchsinger, J.A., Schupf, N., Brickman, A.M., Cosentino, S., Tang, M.X., and Stern, Y. (2009). Physical activity, diet, and risk of Alzheimer disease. J. Am. Med. Assoc. 302, 627–637.10.1001/jama.2009.1144Search in Google Scholar PubMed PubMed Central

Scarmeas, N., Stern, Y., Mayeux, R., and Luchsinger, J.A. (2006). Mediterranean diet, Alzheimer disease, and vascular mediation. Arch. Neurol. 63, 1709–1717.10.1001/archneur.63.12.noc60109Search in Google Scholar PubMed PubMed Central

Schioth, H.B., Craft, S., Brooks, S.J., Frey, 2nd, W.H., , and Benedict, C. (2012). Brain insulin signaling and Alzheimer’s disease: current evidence and future directions. Mol. Neurobiol. 46, 4–10.10.1007/s12035-011-8229-6Search in Google Scholar PubMed PubMed Central

Schnaider, B.M., Goldbourt, U., Silverman, J.M., Noy, S., Schmeidler, J., Ravonaspringer, R., Sverdlick, A., and Davidson, M. (2004). Diabetes mellitus in midlife and the risk of dementia three decades later. Neurology 63, 1902–1907.10.1212/01.WNL.0000144278.79488.DDSearch in Google Scholar

Schwab, K.O., Doerfer, J., Hecker, W., Grulichhenn, J., Wiemann, D., Kordonouri, O., Beyer, P., and Holl, R.W. (2006). Spectrum and prevalence of atherogenic risk factors in 27,358 children, adolescents, and young adults with type 1 diabetes: cross-sectional data from the German diabetes documentation and quality management system (DPV). Diabetes Care 29, 218–225.10.2337/diacare.29.02.06.dc05-0724Search in Google Scholar

Searcy, J.L., Phelps, J.T., Pancani, T., Kadish, I., Popovic, J., Anderson, K.L., Beckett, T.L., Murphy, M.P., Chen, K.C., and Blalock, E.M. (2012). Long-term pioglitazone treatment improves learning and attenuates pathological markers in a mouse model of Alzheimer’s disease. J. Alzheimers Dis. 30, 943–961.10.3233/JAD-2012-111661Search in Google Scholar

Soininen, H., Puranen, M., Helkala, E.L., Laakso, M., and Riekkinen, P.J. (1992). Diabetes mellitus and brain atrophy: a computed tomography study in an elderly population. Neurobiol. Aging 13, 717–721.10.1016/0197-4580(92)90095-FSearch in Google Scholar

Steen, E., Terry, B.M., Rivera, E.J., Cannon, J.L., Neely, T.R., Tavares, R., Xu, X.J., Wands, J.R., and Sm, D.L.M. (2005). Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease – is this type 3 diabetes? J. Alzheimers Dis. 7, 63–80.10.3233/JAD-2005-7107Search in Google Scholar

Stephan, B.C., Hunter, S., Harris, D., Llewellyn, D.J., Siervo, M., Matthews, F.E., and Brayne, C. (2012). The neuropathological profile of mild cognitive impairment (MCI): a systematic review. Mol. Psychiatry 17, 1056–1076.10.1038/mp.2011.147Search in Google Scholar PubMed

Stranahan, A.M., Arumugam, T.V., Cutler, R.G., Lee, K., Egan, J.M., and Mattson, M.P. (2008). Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons. Nat. Neurosci. 11, 309–317.10.1038/nn2055Search in Google Scholar PubMed PubMed Central

Suwa, M., Kishimoto, H., Nofuji, Y., Nakano, H., Sasaki, H., Radak, Z., and Kumagai, S. (2006). Serum brain-derived neurotrophic factor level is increased and associated with obesity in newly diagnosed female patients with type 2 diabetes mellitus. Metabolism 55, 852–857.10.1016/j.metabol.2006.02.012Search in Google Scholar PubMed

Trieu, V.N. and Uckun, F.M. (1999). Genistein is neuroprotective in murine models of familial amyotrophic lateral sclerosis and stroke. Biochem. Biophys. Res. Commun. 258, 685–688.10.1006/bbrc.1999.0577Search in Google Scholar PubMed

Umegaki, H., Kawamura, T., Kawano, N., Umemura, T., Kanai, A., and Sano, T. (2011). Factors associated with cognitive decline in elderly diabetics. Dement. Geriatr. Cogn. Dis. Extra. 1, 1–9.10.1159/000323188Search in Google Scholar PubMed PubMed Central

Van Harten, B., Oosterman, J.M., Potter van Loon, B.J., Scheltens, P., and Weinstein, H.C. (2007). Brain lesions on MRI in elderly patients with type 2 diabetes mellitus. Eur. Neurol. 57, 70–74.10.1159/000098054Search in Google Scholar PubMed

Wang, Z.L., Zou, L., Lu, Z.W., Xie, X.Q., Jia, Z.Z., Pan, C.J., Zhang, G.X., and Ge, X.M. (2017). Abnormal spontaneous brain activity in type 2 diabetic retinopathy revealed by amplitude of low-frequency fluctuations: a resting-state fMRI study. Clin. Radiol. 72, 340.e1–340.e7.10.1016/j.crad.2016.11.012Search in Google Scholar PubMed

Watson, G.S., Cholerton, B.A., Reger, M.A., Baker, L.D., Plymate, S.R., Asthana, S., Fishel, M.A., Kulstad, J.J., Green, P.S., and Cook, D.G. (2005). Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone: a preliminary study. Am. J. Geriatr. Psychiatry 13, 950–958.10.1176/appi.ajgp.13.11.950Search in Google Scholar PubMed

Willis, L.M., Shukitt-Hale, B., and Joseph, J.A. (2009). Recent advances in berry supplementation and age-related cognitive decline. Curr. Opin. Clin. Nutr. Metab. Care 12, 91–94.10.1097/MCO.0b013e32831b9c6eSearch in Google Scholar PubMed

Xia, W., Wang, S., Sun, Z., Bai, F., Zhou, Y., Yang, Y., Wang, P., Huang, Y., and Yuan, Y. (2013). Altered baseline brain activity in type 2 diabetes: a resting-state fMRI study. Psychoneuroendocrinology 38, 2493–2501.10.1016/j.psyneuen.2013.05.012Search in Google Scholar PubMed

Xia, W., Zhang, B., Yang, Y., Wang, P., Yang, Y., and Wang, S. (2015). Poorly controlled cholesterol is associated with cognitive impairment in T2DM: a resting-state fMRI study. Lipids Health Dis. 14, 1–10.10.1186/s12944-015-0046-xSearch in Google Scholar PubMed PubMed Central

Xiongwei, Z., Perry, G., Smith, M.A., and Castellani, R.J. (2008). Current approaches in the treatment of Alzheimer’s disease. Biomed. Pharmacother. 62, 199–207.10.1016/j.biopha.2008.02.005Search in Google Scholar PubMed

Xu, W., Qiu, C., Winblad, B., and Fratiglioni, L. (2007). The effect of borderline diabetes on the risk of dementia and Alzheimer’s disease. Diabetes 56, 211–216.10.2337/db06-0879Search in Google Scholar PubMed

Yaffe, K., Blackwell, T., Kanaya, A.M., Davidowitz, N., Barrettconnor, E., and Krueger, K. (2004). Diabetes, impaired fasting glucose, and development of cognitive impairment in older women. Neurology 63, 658–663.10.1212/01.WNL.0000134666.64593.BASearch in Google Scholar PubMed

Yaffe, K., Blackwell, T., Whitmer, R.A., Krueger, K., and Barrett, C.E. (2006). Glycosylated hemoglobin level and development of mild cognitive impairment or dementia in older women. J. Nutr. Health Aging 10, 293–295.Search in Google Scholar

Yang, C., Devisser, A., Martinez, J.A., Poliakov, I., Rosales-Hernandez, A., Ayer, A., Garven, A., Zaver, S., Rincon, N., and Xu, K. (2011). Retracted: differential impact of diabetes and hypertension in the brain: adverse effects in white matter. Neurobiol. Dis. 44, 161–173.10.1016/j.nbd.2011.02.007Search in Google Scholar PubMed

Yau, P.L., Hempel, R., Tirsi, A., and Convit, A. (2013). Cerebral white matter and retinal arterial health in hypertension and type 2 diabetes mellitus. Int. J. Hypertens. 2013, 329602–329610.10.1155/2013/329602Search in Google Scholar PubMed PubMed Central

Ying, C., Xia, L., Hong, G., Hu, Y., Zhen, Z., Yang, X.Y., Cheng, Q., Yang, Y., and Teng, G.J. (2017). Cerebral perfusion alterations in type 2 diabetes and its relation to insulin resistance and cognitive dysfunction. Brain Imaging Behav. 11, 1248–1257.10.1007/s11682-016-9583-9Search in Google Scholar PubMed PubMed Central

Yuan, X.Y. and Wang, X.G. (2017). Mild cognitive impairment in type 2 diabetes mellitus and related risk factors: a review. Rev. Neurosci. 28, 715–723.10.1515/revneuro-2017-0016Search in Google Scholar PubMed

Zandi, P.P., Anthony, J.C., Khachaturian, A.S., Stone, S.V., Gustafson, D., Tschanz, J.T., Norton, M.C., Welsh-Bohmer, K.A., Breitner, J.C., and Cache County Study Group. (2004). Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study. Arch. Neurol. 61, 82–88.10.1001/archneur.61.1.82Search in Google Scholar PubMed

Zanuso, S., Jimenez, A., Pugliese, G., Corigliano, G., and Balducci, S. (2010). Exercise for the management of type 2 diabetes: a review of the evidence. Acta Diabetol. 47, 15–22.10.1007/s00592-009-0126-3Search in Google Scholar PubMed

Zhang, H., Hao, Y., Manor, B., Novak, P., Milberg, W., Zhang, J., Fang, J., and Novak, V. (2015). Intranasal insulin enhanced resting-state functional connectivity of hippocampal regions in type 2 diabetes. Diabetes 64, 1025–1034.10.2337/db14-1000Search in Google Scholar PubMed PubMed Central

Zhang, J., Liu, Z., Li, Z., Wang, Y., Chen, Y., Li, X., Chen, K., Shu, N., and Zhang, Z. (2016). Disrupted White matter network and cognitive decline in type 2 diabetes patients. J. Alzheimers Dis. 53, 185–195.10.3233/JAD-160111Search in Google Scholar PubMed

Zhao, W.Q. and Townsend, M. (2009). Insulin resistance and amyloidogenesis as common molecular foundation for type 2 diabetes and Alzheimer’s disease. Biochim. Biophys. Acta 1792, 482–496.10.1016/j.bbadis.2008.10.014Search in Google Scholar PubMed

Zheng, T., Gao, Y., Baskota, A., Chen, T., Ran, X., and Tian, H. (2014). Increased plasma DPP4 activity is predictive of prediabetes and type 2 diabetes onset in chinese over a four-year period: result from the china national diabetes and metabolic disorders study. J. Clin. Endocrinol. Metab. 99, 2330–2334.10.1210/jc.2014-1480Search in Google Scholar PubMed

Zheng, T., Chen, T., Liu, Y., Gao, Y., and Tian, H. (2015). Increased plasma DPP4 activity predicts new-onset hypertension in Chinese over a 4-year period: possible associations with inflammation and oxidative stress. J. Hum. Hypertens. 29, 424–429.10.1038/jhh.2014.111Search in Google Scholar PubMed

Zheng, T., Qin, L., Chen, B., Hu, X., Zhang, X., Liu, Y., Liu, H., Qin, S., Li, G., and Li, Q. (2016). Association of plasma DPP4 activity with mild cognitive impairment in elderly patients with type 2 diabetes: results from the GDMD study in China. Diabetes Care 39, 1594–1601.10.2337/dc16-0316Search in Google Scholar PubMed

Zhou, H., Lu, W., Shi, Y., Bai, F., Chang, J., Yuan, Y., Teng, G., and Zhang, Z. (2010). Impairments in cognition and resting-state connectivity of the hippocampus in elderly subjects with type 2 diabetes. Neurosci. Lett. 473, 5–10.10.1016/j.neulet.2009.12.057Search in Google Scholar PubMed