Diabetic Cognitive Dysfunction: From Bench to Clinic

Author(s): Jiyin Zhou, Zuo Zhang, Hongli Zhou, Guisheng Qian*

Journal Name: Current Medicinal Chemistry

Volume 27 , Issue 19 , 2020

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer

Abstract:

Type 2 diabetes increases the risk of developing cognitive dysfunction in the elderly in the form of short-term memory and executive function impairment. Genetic and diet-induced models of type 2 diabetes further support this link, displaying deficits in working memory, learning, and memory performance. The risk factors for diabetic cognitive dysfunction include vascular disease, hypoglycaemia, hyperlipidaemia, adiposity, insulin resistance, lifestyle factors, and genetic factors. Using neuronal imaging technologies, diabetic patients with cognitive dysfunction show atrophy of the whole brain, particularly the grey matter, hippocampus and amygdala; increased volume of the ventricular and white matter; brain infarcts; impaired network integrity; abnormal microstructure; and reduced cerebral blood flow and amplitude of low-frequency fluctuations. The pathogenesis of type 2 diabetes with cognitive dysfunction involves hyperglycaemia, macrovascular and microvascular diseases, insulin resistance, inflammation, apoptosis, and disorders of neurotransmitters. Large clinical trials may offer further proof of biomarkers and risk factors for diabetic cognitive dysfunction. Advanced neuronal imaging technologies and novel disease animal models will assist in elucidating the precise pathogenesis and to provide better therapeutic interventions and treatment.

Keywords: Type 2 diabetes, cognitive dysfunction, hyperglycaemia, insulin resistance, inflammation, vascular disease.

[1]
Formiga, F.; Ferrer, A.; Padrós, G.; Corbella, X.; Cos, L.; Sinclair, A.J.; Rodríguez-Mañas, L. Diabetes mellitus as a risk factor for functional and cognitive decline in very old people: the Octabaix study. J. Am. Med. Dir. Assoc., 2014, 15(12), 924-928.
[http://dx.doi.org/10.1016/j.jamda.2014.07.019] [PMID: 25271193]
[2]
Singh-Manoux, A.; Schmidt, R. Diabetes: A risk factor for cognitive impairment and dementia? Neurology, 2015, 84(23), 2300-2301.
[http://dx.doi.org/10.1212/WNL.0000000000001671] [PMID: 25948721]
[3]
Cukierman, T.; Gerstein, H.C.; Williamson, J.D. Cognitive decline and dementia in diabetes--systematic overview of prospective observational studies. Diabetologia, 2005, 48(12), 2460-2469.
[http://dx.doi.org/10.1007/s00125-005-0023-4] [PMID: 16283246]
[4]
Keskin, F.E.; Ozyazar, M.; Pala, A.S.; Elmali, A.D.; Yilmaz, B.; Uygunoglu, U.; Bozluolcay, M.; Tuten, A.; Bingöl, A.; Hatipoglu, E. Evaluation of cognitive functions in gestational diabetes mellitus. Exp. Clin. Endocrinol. Diabetes, 2015, 123(4), 246-251.
[http://dx.doi.org/10.1055/s-0034-1395634] [PMID: 25868060]
[5]
Biessels, G.J.; Deary, I.J.; Ryan, C.M. Cognition and diabetes: a lifespan perspective. Lancet Neurol., 2008, 7(2), 184-190.
[http://dx.doi.org/10.1016/S1474-4422(08)70021-8] [PMID: 18207116]
[6]
McCrimmon, R.J.; Ryan, C.M.; Frier, B.M. Diabetes and cognitive dysfunction. Lancet, 2012, 379(9833), 2291-2299.
[http://dx.doi.org/10.1016/S0140-6736(12)60360-2] [PMID: 22683129]
[7]
Sadanand, S.; Balachandar, R.; Bharath, S. Memory and executive functions in persons with type 2 diabetes: a meta-analysis. Diabetes Metab. Res. Rev., 2016, 32(2), 132-142.
[http://dx.doi.org/10.1002/dmrr.2664] [PMID: 25963303]
[8]
Tomlin, A.; Sinclair, A. The influence of cognition on self-management of type 2 diabetes in older people. Psychol. Res. Behav. Manag., 2016, 9, 7-20.
[http://dx.doi.org/10.2147/PRBM.S36238] [PMID: 26855601]
[9]
Gao, Y.; Xiao, Y.; Miao, R.; Zhao, J.; Zhang, W.; Huang, G.; Ma, F. The characteristic of cognitive function in Type 2 diabetes mellitus. Diabetes Res. Clin. Pract., 2015, 109(2), 299-305.
[http://dx.doi.org/10.1016/j.diabres.2015.05.019] [PMID: 26004430]
[10]
Nazaribadie, M.; Asgari, K.; Amini, M.; Ahmadpanah, M.; Nazaribadie, M.; Jamlipaghale, S. Cognitive processes and functions in patients with type 2 diabetes in comparison to pre-diabetic patients. J. Res. Health Sci., 2013, 13(2), 208-213.
[PMID: 24077481]
[11]
Feinkohl, I.; Price, J.F.; Strachan, M.W.; Frier, B.M. The impact of diabetes on cognitive decline: potential vascular, metabolic, and psychosocial risk factors. Alzheimers Res. Ther., 2015, 7(1), 46.
[http://dx.doi.org/10.1186/s13195-015-0130-5] [PMID: 26060511]
[12]
Moulton, C.D.; Stewart, R.; Amiel, S.A.; Laake, J.P.; Ismail, K. Factors associated with cognitive impairment in patients with newly diagnosed type 2 diabetes: a cross-sectional study. Aging Ment. Health, 2016, 20(8), 840-847.
[http://dx.doi.org/10.1080/13607863.2015.1040723] [PMID: 25959123]
[13]
Katon, W.; Lyles, C.R.; Parker, M.M.; Karter, A.J.; Huang, E.S.; Whitmer, R.A. Association of depression with increased risk of dementia in patients with type 2 diabetes: the Diabetes and Aging Study. Arch. Gen. Psychiatry, 2012, 69(4), 410-417.
[http://dx.doi.org/10.1001/archgenpsychiatry.2011.154] [PMID: 22147809]
[14]
Marioni, R.E.; Strachan, M.W.; Reynolds, R.M.; Lowe, G.D.; Mitchell, R.J.; Fowkes, F.G.; Frier, B.M.; Lee, A.J.; Butcher, I.; Rumley, A.; Murray, G.D.; Deary, I.J.; Price, J.F. Association between raised inflammatory markers and cognitive decline in elderly people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study. Diabetes, 2010, 59(3), 710-713.
[http://dx.doi.org/10.2337/db09-1163] [PMID: 19959761]
[15]
Pantoni, L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol., 2010, 9(7), 689-701.
[http://dx.doi.org/10.1016/S1474-4422(10)70104-6] [PMID: 20610345]
[16]
Feinkohl, I.; Keller, M.; Robertson, C.M.; Morling, J.R.; Williamson, R.M.; Nee, L.D.; McLachlan, S.; Sattar, N.; Welsh, P.; Reynolds, R.M.; Russ, T.C.; Deary, I.J.; Strachan, M.W.; Price, J.F. Edinburgh Type 2 Diabetes Study (ET2DS) Investigators. Clinical and subclinical macrovascular disease as predictors of cognitive decline in older patients with type 2 diabetes: the Edinburgh Type 2 Diabetes Study. Diabetes Care, 2013, 36(9), 2779-2786.
[http://dx.doi.org/10.2337/dc12-2241] [PMID: 23579182]
[17]
Ravona-Springer, R.; Haratz, S.; Tanne, D.; Schmeidler, J.; Efrati, S.; Rosendorff, C.; Beeri, M.S.; Silverman, J.M. Arterial wall function is associated with cognitive performance primarily in elderly with type 2 diabetes. J. Alzheimers Dis., 2015, 44(2), 687-693.
[http://dx.doi.org/10.3233/JAD-141197] [PMID: 25352451]
[18]
Naidu, V.V.; Ismail, K.; Amiel, S.; Kohli, R.; Crosby-Nwaobi, R.; Sivaprasad, S.; Stewart, R. Crosby- Nwaobi, R.; Sivaprasad, S.; Stewart, R. Associations between retinal markers of microvascular disease and cognitive impairment in newly diagnosed type 2 diabetes mellitus: a case control study. PLoS One, 2016, 11(1) e0147160
[http://dx.doi.org/10.1371/journal.pone.0147160] [PMID: 26771382]
[19]
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(13), 1195-1202.
[http://dx.doi.org/10.1212/WNL.0b013e3181f4d7f8] [PMID: 20739645]
[20]
Nelson, P.T.; Smith, C.D.; Abner, E.A.; Schmitt, F.A.; Scheff, S.W.; Davis, G.J.; Keller, J.N.; Jicha, G.A.; Davis, D.; Wang-Xia, W.; Hartman, A.; Katz, D.G.; Markesbery, W.R. Human cerebral neuropathology of Type 2 diabetes mellitus. Biochim. Biophys. Acta, 2009, 1792(5), 454-469.
[http://dx.doi.org/10.1016/j.bbadis.2008.08.005] [PMID: 18789386]
[21]
Xu, W.L.; Qiu, C.X.; 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(7), 1181-1186.
[http://dx.doi.org/10.1212/01.WNL.0000140291.86406.D1] [PMID: 15477535]
[22]
Umegaki, H.; Iimuro, S.; Shinozaki, T.; Araki, A.; Sakurai, T.; Iijima, K.; Ohashi, Y.; Ito, H. Japanese Elderly Diabetes Intervention Trial Study Group. Risk factors associated with cognitive decline in the elderly with type 2 diabetes: pooled logistic analysis of a 6-year observation in the Japanese Elderly Diabetes Intervention Trial. Geriatr. Gerontol. Int., 2012, 12(Suppl. 1), 110-116.
[http://dx.doi.org/10.1111/j.1447-0594.2011.00818.x] [PMID: 22435946]
[23]
Bruce, D.G.; Davis, W.A.; Casey, G.P.; Starkstein, S.E.; Clarnette, R.M.; Almeida, O.P.; Davis, T.M.E. Predictors of cognitive decline in older individuals with diabetes. Diabetes Care, 2008, 31(11), 2103-2107.
[http://dx.doi.org/10.2337/dc08-0562] [PMID: 18650375]
[24]
Johnson, M.L.; Parikh, N.; Kunik, M.E.; Schulz, P.E.; Patel, J.G.; Chen, H.; Aparasu, R.R.; Morgan, R.O. Antihypertensive drug use and the risk of dementia in patients with diabetes mellitus. Alzheimers Dement., 2012, 8(5), 437-444.
[http://dx.doi.org/10.1016/j.jalz.2011.05.2414] [PMID: 22521970]
[25]
Manschot, S.M.; Biessels, G.J.; de Valk, H.; Algra, A.; Rutten, G.E.; van der Grond, J.; Kappelle, L.J. Utrecht Diabetic Encephalopathy Study Group. Metabolic and vascular determinants of impaired cognitive performance and abnormalities on brain magnetic resonance imaging in patients with type 2 diabetes. Diabetologia, 2007, 50(11), 2388-2397.
[http://dx.doi.org/10.1007/s00125-007-0792-z] [PMID: 17764005]
[26]
van den Berg, E.; Dekker, J.M.; Nijpels, G.; Kessels, R.P.; Kappelle, L.J.; de Haan, E.H.; Heine, R.J.; Stehouwer, C.D.; Biessels, G.J. Blood pressure levels in pre-diabetic stages are associated with worse cognitive functioning in patients with type 2 diabetes. Diabetes Metab. Res. Rev., 2009, 25(7), 657-664.
[http://dx.doi.org/10.1002/dmrr.1009] [PMID: 19768735]
[27]
Roberts, R.O.; Knopman, D.S.; Przybelski, S.A.; Mielke, M.M.; Kantarci, K.; Preboske, G.M.; Senjem, M.L.; Pankratz, V.S.; Geda, Y.E.; Boeve, B.F.; Ivnik, R.J.; Rocca, W.A.; Petersen, R.C.; Jack, C.R., Jr Association of type 2 diabetes with brain atrophy and cognitive impairment. Neurology, 2014, 82(13), 1132-1141.
[http://dx.doi.org/10.1212/WNL.0000000000000269] [PMID: 24647028]
[28]
Lee, A.K.; Rawlings, A.M.; Lee, C.J.; Gross, A.L.; Huang, E.S.; Sharrett, A.R.; Coresh, J.; Selvin, E. Severe hypoglycaemia, mild cognitive impairment, dementia and brain volumes in older adults with type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) cohort study. Diabetologia, 2018, 61(9), 1956-1965.
[http://dx.doi.org/10.1007/s00125-018-4668-1] [PMID: 29961106]
[29]
Allen, K.V.; Pickering, M.J.; Zammitt, N.N.; Hartsuiker, R.J.; Traxler, M.J.; Frier, B.M.; Deary, I.J. Effects of acute hypoglycemia on working memory and language processing in adults with and without type 1 diabetes. Diabetes Care, 2015, 38(6), 1108-1115.
[http://dx.doi.org/10.2337/dc14-1657] [PMID: 25758768]
[30]
Whitmer, R.A.; Karter, A.J.; Yaffe, K.; Quesenberry, C.P., Jr; Selby, J.V. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA, 2009, 301(15), 1565-1572.
[http://dx.doi.org/10.1001/jama.2009.460] [PMID: 19366776]
[31]
Bruce, D.G.; Davis, W.A.; Casey, G.P.; Clarnette, R.M.; Brown, S.G.; Jacobs, I.G.; Almeida, O.P.; Davis, T.M. Severe hypoglycaemia and cognitive impairment in older patients with diabetes: the Fremantle Diabetes Study. Diabetologia, 2009, 52(9), 1808-1815.
[http://dx.doi.org/10.1007/s00125-009-1437-1] [PMID: 19575177]
[32]
Yaffe, K.; Falvey, C.M.; Hamilton, N.; Harris, T.B.; Simonsick, E.M.; Strotmeyer, E.S.; Shorr, R.I.; Metti, A.; Schwartz, A.V.; Health, A.B.C.S. Health ABC Study. Association between hypoglycemia and dementia in a biracial cohort of older adults with diabetes mellitus. JAMA Intern. Med., 2013, 173(14), 1300-1306.
[http://dx.doi.org/10.1001/jamainternmed.2013.6176] [PMID: 23753199]
[33]
de Galan, B.E.; Zoungas, S.; Chalmers, J.; Anderson, C.; Dufouil, C.; Pillai, A.; Cooper, M.; Grobbee, D.E.; Hackett, M.; Hamet, P.; Heller, S.R.; Lisheng, L.; MacMahon, S.; Mancia, G.; Neal, B.; Pan, C.Y.; Patel, A.; Poulter, N.; Travert, F.; Woodward, M. ADVANCE Collaborative group. Cognitive function and risks of cardiovascular disease and hypoglycaemia in patients with type 2 diabetes: the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Diabetologia, 2009, 52(11), 2328-2336.
[http://dx.doi.org/10.1007/s00125-009-1484-7] [PMID: 19688336]
[34]
Punthakee, Z.; Miller, M.E.; Launer, L.J.; Williamson, J.D.; Lazar, R.M.; Cukierman-Yaffee, T.; Seaquist, E.R.; Ismail-Beigi, F.; Sullivan, M.D.; Lovato, L.C.; Bergenstal, R.M.; Gerstein, H.C. Poor cognitive function and risk of severe hypoglycemia in type 2 diabetes: post hoc epidemiologic analysis of the ACCORD trial. Diabetes Care, 2012, 35(4), 787-793.
[http://dx.doi.org/10.2337/dc11-1855] [PMID: 22374637]
[35]
Isik, A.T.; Soysal, P.; Yay, A.; Usarel, C. The effects of sitagliptin, a DPP-4 inhibitor, on cognitive functions in elderly diabetic patients with or without Alzheimer’s disease. Diabetes Res. Clin. Pract., 2017, 123, 192-198.
[http://dx.doi.org/10.1016/j.diabres.2016.12.010] [PMID: 28056430]
[36]
Barnes, D.E.; Yaffe, K. The projected effect of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol., 2011, 10(9), 819-828.
[http://dx.doi.org/10.1016/S1474-4422(11)70072-2] [PMID: 21775213]
[37]
Kloppenborg, R.P.; van den Berg, E.; Kappelle, L.J.; Biessels, G.J. Diabetes and other vascular risk factors for dementia: which factor matters most? A systematic review. Eur. J. Pharmacol., 2008, 585(1), 97-108.
[http://dx.doi.org/10.1016/j.ejphar.2008.02.049] [PMID: 18395201]
[38]
Reitz, C. Dyslipidemia and dementia: current epidemiology, genetic evidence, and mechanisms behind the associations. J. Alzheimers Dis., 2012, 30(Suppl. 2), S127-S145.
[http://dx.doi.org/10.3233/JAD-2011-110599] [PMID: 21965313]
[39]
Bruce, D.G.; Davis, W.A.; Casey, G.P.; Starkstein, S.E.; Clarnette, R.M.; Foster, J.K.; Almeida, O.P.; Davis, T.M. Predictors of cognitive impairment and dementia in older people with diabetes. Diabetologia, 2008, 51(2), 241-248.
[http://dx.doi.org/10.1007/s00125-007-0894-7] [PMID: 18060658]
[40]
Xia, W.; Zhang, B.; Yang, Y.; Wang, P.; Yang, Y.; Wang, S. Poorly controlled cholesterol is associated with cognitive impairment in T2DM: a resting-state fMRI study. Lipids Health Dis., 2015, 14, 47.
[http://dx.doi.org/10.1186/s12944-015-0046-x] [PMID: 25989796]
[41]
Abbatecola, A.M.; Lattanzio, F.; Spazzafumo, L.; Molinari, A.M.; Cioffi, M.; Canonico, R.; Dicioccio, L.; Paolisso, G. Adiposity predicts cognitive decline in older persons with diabetes: a 2-year follow-up. PLoS One, 2010, 5(4) e10333
[http://dx.doi.org/10.1371/journal.pone.0010333] [PMID: 20428239]
[42]
Whitmer, R.A.; Gunderson, E.P.; Barrett-Connor, E.; Quesenberry, C.P., Jr; Yaffe, K. Obesity in middle age and future risk of dementia: a 27 year longitudinal population based study. BMJ, 2005, 330(7504), 1360.
[http://dx.doi.org/10.1136/bmj.38446.466238.E0] [PMID: 15863436]
[43]
Anstey, K.J.; Cherbuin, N.; Budge, M.; Young, J. Body mass index in midlife and late-life as a risk factor for dementia: a meta-analysis of prospective studies. Obes. Rev., 2011, 12(5), e426-e437.
[http://dx.doi.org/10.1111/j.1467-789X.2010.00825.x] [PMID: 21348917]
[44]
Morris, J.K.; Vidoni, E.D.; Honea, R.A.; Burns, J.M. Impaired glycemia increases disease progression in mild cognitive impairment. Neurobiol. Aging, 2014, 35(3), 585-589.
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.09.033] [PMID: 24411018]
[45]
Ma, L.; Wang, J.; Li, Y. Insulin resistance and cognitive dysfunction. Clin. Chim. Acta, 2015, 444, 18-23.
[http://dx.doi.org/10.1016/j.cca.2015.01.027] [PMID: 25661087]
[46]
Ma, L.; Li, Y. Cognitive function and insulin resistance in elderly patients with type 2 diabetes. Neurol. Res., 2017, 39(3), 259-263.
[http://dx.doi.org/10.1080/01616412.2017.1281199] [PMID: 28107806]
[47]
de Senna, P.N.; Xavier, L.L.; Bagatini, P.B.; Saur, L.; Galland, F.; Zanotto, C.; Bernardi, C.; Nardin, P.; Gonçalves, C.A.; Achaval, M. Physical training improves non-spatial memory, locomotor skills and the blood brain barrier in diabetic rats. Brain Res., 2015, 1618, 75-82.
[http://dx.doi.org/10.1016/j.brainres.2015.05.026] [PMID: 26032744]
[48]
Devore, E.E.; Kang, J.H.; Okereke, O.; Grodstein, F. Physical activity levels and cognition in women with type 2 diabetes. Am. J. Epidemiol., 2009, 170(8), 1040-1047.
[http://dx.doi.org/10.1093/aje/kwp224] [PMID: 19729385]
[49]
Devore, E.E.; Stampfer, M.J.; Breteler, M.M.; Rosner, B.; Kang, J.H.; Okereke, O.; Hu, F.B.; Grodstein, F. Dietary fat intake and cognitive decline in women with type 2 diabetes. Diabetes Care, 2009, 32(4), 635-640.
[http://dx.doi.org/10.2337/dc08-1741] [PMID: 19336640]
[50]
West, R.K.; Ravona-Springer, R.; Heymann, A.; Schmeidler, J.; Leroith, D.; Koifman, K.; Guerrero-Berroa, E.; Preiss, R.; Hoffman, H.; Silverman, J.M.; Beeri, M.S. Shorter adult height is associated with poorer cognitive performance in elderly men with type II diabetes. J. Alzheimers Dis., 2015, 44(3), 927-935.
[http://dx.doi.org/10.3233/JAD-142049] [PMID: 25374105]
[51]
Sanke, H.; Mita, T.; Yoshii, H.; Yokota, A.; Yamashiro, K.; Ingaki, N.; Onuma, T.; Someya, Y.; Komiya, K.; Tamura, Y.; Shimizu, T.; Ohmura, C.; Kanazawa, A.; Fujitani, Y.; Watada, H. Relationship between olfactory dysfunction and cognitive impairment in elderly patients with type 2 diabetes mellitus. Diabetes Res. Clin. Pract., 2014, 106(3), 465-473.
[http://dx.doi.org/10.1016/j.diabres.2014.09.039] [PMID: 25451914]
[52]
Guerrero-Berroa, E.; Ravona-Springer, R.; Heymann, A.; Schmeidler, J.; Levy, A.; Leroith, D.; Beeri, M.S. Haptoglobin genotype modulates the relationships of glycaemic control with cognitive function in elderly individuals with type 2 diabetes. Diabetologia, 2015, 58(4), 736-744.
[http://dx.doi.org/10.1007/s00125-014-3487-2] [PMID: 25628235]
[53]
Xie, J.; Wei, Q.; Deng, H.; Li, G.; Ma, L.; Zeng, H. Negative regulation of Grb10 Interacting GYF Protein 2 on insulin-like growth factor-1 receptor signaling pathway caused diabetic mice cognitive impairment. PLoS One, 2014, 9(9) e108559
[http://dx.doi.org/10.1371/journal.pone.0108559] [PMID: 25268761]
[54]
Yang, R.; Chen, R.P.; Chen, H.; Zhang, H.; Cai, D.H. Folic acid attenuates cognitive dysfunction in streptozotocin-induced diabetic rats. Int. J. Clin. Exp. Med., 2014, 7(11), 4214-4219.
[PMID: 25550933]
[55]
Taylor, S.L.; Trudeau, D.; Arnold, B.; Wang, J.; Gerrow, K.; Summerfeldt, K.; Holmes, A.; Zamani, A.; Brocardo, P.S.; Brown, C.E. VEGF can protect against blood brain barrier dysfunction, dendritic spine loss and spatial memory impairment in an experimental model of diabetes. Neurobiol. Dis., 2015, 78, 1-11.
[http://dx.doi.org/10.1016/j.nbd.2015.03.022] [PMID: 25829228]
[56]
Xiang, Q.; Zhang, J.; Li, C.Y.; Wang, Y.; Zeng, M.J.; Cai, Z.X.; Tian, R.B.; Jia, W.; Li, X.H. Insulin resistance-induced hyperglycemia decreased the activation of Akt/CREB in hippocampus neurons: Molecular evidence for mechanism of diabetes-induced cognitive dysfunction. Neuropeptides, 2015, 54, 9-15.
[http://dx.doi.org/10.1016/j.npep.2015.08.009] [PMID: 26344332]
[57]
Winkler, A.; Dlugaj, M.; Weimar, C.; Jöckel, K.H.; Erbel, R.; Dragano, N.; Moebus, S. Association of diabetes mellitus and mild cognitive impairment in middle-aged men and women. J. Alzheimers Dis., 2014, 42(4), 1269-1277.
[http://dx.doi.org/10.3233/JAD-140696] [PMID: 25024326]
[58]
van Agtmaal, M.J.M.; Houben, A.J.H.M.; de Wit, V.; Henry, R.M.A.; Schaper, N.C.; Dagnelie, P.C.; van der Kallen, C.J.; Koster, A.; Sep, S.J.; Kroon, A.A.; Jansen, J.F.A.; Hofman, P.A.; Backes, W.H.; Schram, M.T.; Stehouwer, C.D.A. Prediabetes is associated with structural brain abnormalities: the Maastricht study. Diabetes Care, 2018, 41(12), 2535-2543.
[http://dx.doi.org/10.2337/dc18-1132] [PMID: 30327356]
[59]
Luchsinger, J.A. Type 2 diabetes and cognitive impairment: linking mechanisms. J. Alzheimers Dis., 2012, 30(Suppl. 2), S185-S198.
[http://dx.doi.org/10.3233/JAD-2012-111433] [PMID: 22433668]
[60]
Bohnen, N.I.; Kotagal, V.; Müller, M.L.; Koeppe, R.A.; Scott, P.J.; Albin, R.L.; Frey, K.A.; Petrou, M. Diabetes mellitus is independently associated with more severe cognitive impairment in Parkinson disease. Parkinsonism Relat. Disord., 2014, 20(12), 1394-1398.
[http://dx.doi.org/10.1016/j.parkreldis.2014.10.008] [PMID: 25454317]
[61]
Wardlaw, J.M.; Smith, E.E.; Biessels, G.J.; Cordonnier, C.; Fazekas, F.; Frayne, R.; Lindley, R.I.; O’Brien, J.T.; Barkhof, F.; Benavente, O.R.; Black, S.E.; Brayne, C.; Breteler, M.; Chabriat, H.; Decarli, C.; de Leeuw, F.E.; Doubal, F.; Duering, M.; Fox, N.C.; Greenberg, S.; Hachinski, V.; Kilimann, I.; Mok, V.; Oostenbrugge, Rv.; Pantoni, L.; Speck, O.; Stephan, B.C.; Teipel, S.; Viswanathan, A.; Werring, D.; Chen, C.; Smith, C.; van Buchem, M.; Norrving, B.; Gorelick, P.B.; Dichgans, M. STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1). Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol., 2013, 12(8), 822-838.
[http://dx.doi.org/10.1016/S1474-4422(13)70124-8] [PMID: 23867200]
[62]
Espeland, M.A.; Bryan, R.N.; Goveas, J.S.; Robinson, J.G.; Siddiqui, M.S.; Liu, S.; Hogan, P.E.; Casanova, R.; Coker, L.H.; Yaffe, K.; Masaki, K.; Rossom, R.; Resnick, S.M. WHIMS-MRI Study Group. Influence of type 2 diabetes on brain volumes and changes in brain volumes: results from the Women’s Health Initiative Magnetic Resonance Imaging studies. Diabetes Care, 2013, 36(1), 90-97.
[http://dx.doi.org/10.2337/dc12-0555] [PMID: 22933440]
[63]
Ma, M.; Hasegawa, Y.; Koibuchi, N.; Toyama, K.; Uekawa, K.; Nakagawa, T.; Lin, B.; Kim-Mitsuyama, S. DPP-4 inhibition with linagliptin ameliorates cognitive impairment and brain atrophy induced by transient cerebral ischemia in type 2 diabetic mice. Cardiovasc. Diabetol., 2015, 14, 54.
[http://dx.doi.org/10.1186/s12933-015-0218-z] [PMID: 25986579]
[64]
Reijmer, Y.D.; van den Berg, E.; Ruis, C.; Kappelle, L.J.; Biessels, G.J. Cognitive dysfunction in patients with type 2 diabetes. Diabetes Metab. Res. Rev., 2010, 26(7), 507-519.
[http://dx.doi.org/10.1002/dmrr.1112] [PMID: 20799243]
[65]
van Harten, B.; de Leeuw, F.E.; Weinstein, H.C.; Scheltens, P.; Biessels, G.J. Brain imaging in patients with diabetes: a systematic review. Diabetes Care, 2006, 29(11), 2539-2548.
[http://dx.doi.org/10.2337/dc06-1637] [PMID: 17065699]
[66]
Manschot, S.M.; Brands, A.M.; van der Grond, J.; Kessels, R.P.; Algra, A.; Kappelle, L.J.; Biessels, G.J. Utrecht Diabetic Encephalopathy Study Group. Brain magnetic resonance imaging correlates of impaired cognition in patients with type 2 diabetes. Diabetes, 2006, 55(4), 1106-1113.
[http://dx.doi.org/10.2337/diabetes.55.04.06.db05-1323] [PMID: 16567535]
[67]
Korf, E.S.; van Straaten, E.C.; de Leeuw, F.E.; van der Flier, W.M.; Barkhof, F.; Pantoni, L.; Basile, A.M.; Inzitari, D.; Erkinjuntti, T.; Wahlund, L.O.; Rostrup, E.; Schmidt, R.; Fazekas, F.; Scheltens, P.; Group, L.S. LADIS Study Group. Diabetes mellitus, hypertension and medial temporal lobe atrophy: the LADIS study. Diabet. Med., 2007, 24(2), 166-171.
[http://dx.doi.org/10.1111/j.1464-5491.2007.02049.x] [PMID: 17257279]
[68]
Last, D.; Alsop, D.C.; Abduljalil, A.M.; Marquis, R.P.; de Bazelaire, C.; Hu, K.; Cavallerano, J.; Novak, V. Global and regional effects of type 2 diabetes on brain tissue volumes and cerebral vasoreactivity. Diabetes Care, 2007, 30(5), 1193-1199.
[http://dx.doi.org/10.2337/dc06-2052] [PMID: 17290035]
[69]
Gold, S.M.; Dziobek, I.; Sweat, V.; Tirsi, A.; Rogers, K.; Bruehl, H.; Tsui, W.; Richardson, S.; Javier, E.; Convit, A. Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes. Diabetologia, 2007, 50(4), 711-719.
[http://dx.doi.org/10.1007/s00125-007-0602-7] [PMID: 17334649]
[70]
Bruehl, H.; Wolf, O.T.; Sweat, V.; Tirsi, A.; Richardson, S.; Convit, A. Modifiers of cognitive function and brain structure in middle-aged and elderly individuals with type 2 diabetes mellitus. Brain Res., 2009, 1280, 186-194.
[http://dx.doi.org/10.1016/j.brainres.2009.05.032] [PMID: 19463794]
[71]
Burns, J.M.; Donnelly, J.E.; Anderson, H.S.; Mayo, M.S.; Spencer-Gardner, L.; Thomas, G.; Cronk, B.B.; Haddad, Z.; Klima, D.; Hansen, D.; Brooks, W.M. Peripheral insulin and brain structure in early Alzheimer disease. Neurology, 2007, 69(11), 1094-1104.
[http://dx.doi.org/10.1212/01.wnl.0000276952.91704.af] [PMID: 17846409]
[72]
Burns, J.M.; Honea, R.A.; Vidoni, E.D.; Hutfles, L.J.; Brooks, W.M.; Swerdlow, R.H. Insulin is differentially related to cognitive decline and atrophy in Alzheimer’s disease and aging. Biochim. Biophys. Acta, 2012, 1822(3), 333-339.
[http://dx.doi.org/10.1016/j.bbadis.2011.06.011] [PMID: 21745566]
[73]
de Bresser, J.; Tiehuis, A.M.; van den Berg, E.; Reijmer, Y.D.; Jongen, C.; Kappelle, L.J.; Mali, W.P.; Viergever, M.A.; Biessels, G.J. Utrecht Diabetic Encephalopathy Study Group. Progression of cerebral atrophy and white matter hyperintensities in patients with type 2 diabetes. Diabetes Care, 2010, 33(6), 1309-1314.
[http://dx.doi.org/10.2337/dc09-1923] [PMID: 20299484]
[74]
Falvey, C.M.; Rosano, C.; Simonsick, E.M.; Harris, T.; Strotmeyer, E.S.; Satterfield, S.; Yaffe, K.; Health, A.B.C.S. Health ABC Study. Macro- and microstructural magnetic resonance imaging indices associated with diabetes among community-dwelling older adults. Diabetes Care, 2013, 36(3), 677-682.
[http://dx.doi.org/10.2337/dc12-0814] [PMID: 23160721]
[75]
Saczynski, J.S.; Siggurdsson, S.; Jonsson, P.V.; Eiriksdottir, G.; Olafsdottir, E.; Kjartansson, O.; Harris, T.B.; van Buchem, M.A.; Gudnason, V.; Launer, L.J. Glycemic status and brain injury in older individuals: the age gene/environment susceptibility-Reykjavik study. Diabetes Care, 2009, 32(9), 1608-1613.
[http://dx.doi.org/10.2337/dc08-2300] [PMID: 19509008]
[76]
Moran, C.; Phan, T.G.; Chen, J.; Blizzard, L.; Beare, R.; Venn, A.; Münch, G.; Wood, A.G.; Forbes, J.; Greenaway, T.M.; Pearson, S.; Srikanth, V. Brain atrophy in type 2 diabetes: regional distribution and influence on cognition. Diabetes Care, 2013, 36(12), 4036-4042.
[http://dx.doi.org/10.2337/dc13-0143] [PMID: 23939539]
[77]
García-Casares, N.; Jorge, R.E.; García-Arnés, J.A.; Acion, L.; Berthier, M.L.; Gonzalez-Alegre, P.; Nabrozidis, A.; Gutiérrez, A.; Ariza, M.J.; Rioja, J.; González-Santos, P. Cognitive dysfunctions in middle-aged type 2 diabetic patients and neuroimaging correlations: a cross-sectional study. J. Alzheimers Dis., 2014, 42(4), 1337-1346.
[http://dx.doi.org/10.3233/JAD-140702] [PMID: 25024335]
[78]
Willette, A.A.; Xu, G.; Johnson, S.C.; Birdsill, A.C.; Jonaitis, E.M.; Sager, M.A.; Hermann, B.P.; La Rue, A.; Asthana, S.; Bendlin, B.B. Insulin resistance, brain atrophy, and cognitive performance in late middle-aged adults. Diabetes Care, 2013, 36(2), 443-449.
[http://dx.doi.org/10.2337/dc12-0922] [PMID: 23069842]
[79]
van Duinkerken, E.; Ijzerman, R.G.; Klein, M.; Moll, A.C.; Snoek, F.J.; Scheltens, P.; Pouwels, P.J.; Barkhof, F.; Diamant, M.; Tijms, B.M. Disrupted subject-specific gray matter network properties and cognitive dysfunction in type 1 diabetes patients with and without proliferative retinopathy. Hum. Brain Mapp., 2016, 37(3), 1194-1208.
[http://dx.doi.org/10.1002/hbm.23096] [PMID: 26700243]
[80]
den Heijer, T.; Vermeer, S.E.; van Dijk, E.J.; Prins, N.D.; Koudstaal, P.J.; Hofman, A.; Breteler, M.M. Type 2 diabetes and atrophy of medial temporal lobe structures on brain MRI. Diabetologia, 2003, 46(12), 1604-1610.
[http://dx.doi.org/10.1007/s00125-003-1235-0] [PMID: 14595538]
[81]
Zhang, Y.W.; Zhang, J.Q.; Liu, C.; Wei, P.; Zhang, X.; Yuan, Q.Y.; Yin, X.T.; Wei, L.Q.; Cui, J.G.; Wang, J. Memory dysfunction in type 2 diabetes mellitus correlates with reduced hippocampal CA1 and subiculum volumes. Chin. Med. J. (Engl.), 2015, 128(4), 465-471.
[http://dx.doi.org/10.4103/0366-6999.151082] [PMID: 25673447]
[82]
Korf, E.S.; White, L.R.; Scheltens, P.; Launer, L.J. Brain aging in very old men with type 2 diabetes: the Honolulu-Asia Aging Study. Diabetes Care, 2006, 29(10), 2268-2274.
[http://dx.doi.org/10.2337/dc06-0243] [PMID: 17003305]
[83]
Hishikawa, N.; Yamashita, T.; Deguchi, K.; Wada, J.; Shikata, K.; Makino, H.; Abe, K. Cognitive and affective functions in diabetic patients associated with diabetes-related factors, white matter abnormality and aging. Eur. J. Neurol., 2015, 22(2), 313-321.
[http://dx.doi.org/10.1111/ene.12568] [PMID: 25220803]
[84]
Reijmer, Y.D.; van den Berg, E.; de Bresser, J.; Kessels, R.P.; Kappelle, L.J.; Algra, A.; Biessels, G.J. Utrecht Diabetic Encephalopathy Study Group. Accelerated cognitive decline in patients with type 2 diabetes: MRI correlates and risk factors. Diabetes Metab. Res. Rev., 2011, 27(2), 195-202.
[http://dx.doi.org/10.1002/dmrr.1163] [PMID: 21294241]
[85]
Reijmer, Y.D.; Brundel, M.; de Bresser, J.; Kappelle, L.J.; Leemans, A.; Biessels, G.J. Utrecht Vascular Cognitive Impairment Study Group. Microstructural white matter abnormalities and cognitive functioning in type 2 diabetes: a diffusion tensor imaging study. Diabetes Care, 2013, 36(1), 137-144.
[http://dx.doi.org/10.2337/dc12-0493] [PMID: 22961577]
[86]
Reijmer, Y.D.; Leemans, A.; Brundel, M.; Kappelle, L.J.; Biessels, G.J. Utrecht Vascular Cognitive Impairment Study Group. Disruption of the cerebral white matter network is related to slowing of information processing speed in patients with type 2 diabetes. Diabetes, 2013, 62(6), 2112-2115.
[http://dx.doi.org/10.2337/db12-1644] [PMID: 23349494]
[87]
Luitse, M.J.; Biessels, G.J.; Rutten, G.E.; Kappelle, L.J. Diabetes, hyperglycaemia, and acute ischaemic stroke. Lancet Neurol., 2012, 11(3), 261-271.
[http://dx.doi.org/10.1016/S1474-4422(12)70005-4] [PMID: 22341034]
[88]
Cordonnier, C.; Al-Shahi Salman, R.; Wardlaw, J. Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting. Brain, 2007, 130(Pt 8), 1988-2003.
[http://dx.doi.org/10.1093/brain/awl387] [PMID: 17322562]
[89]
Novak, V.; Last, D.; Alsop, D.C.; Abduljalil, A.M.; Hu, K.; Lepicovsky, L.; Cavallerano, J.; Lipsitz, L.A. Cerebral blood flow velocity and periventricular white matter hyperintensities in type 2 diabetes. Diabetes Care, 2006, 29(7), 1529-1534.
[http://dx.doi.org/10.2337/dc06-0261] [PMID: 16801574]
[90]
Sabri, O.; Hellwig, D.; Schreckenberger, M.; Schneider, R.; Kaiser, H.J.; Wagenknecht, G.; Mull, M.; Buell, U. Influence of diabetes mellitus on regional cerebral glucose metabolism and regional cerebral blood flow. Nucl. Med. Commun., 2000, 21(1), 19-29.
[http://dx.doi.org/10.1097/00006231-200001000-00005] [PMID: 10717898]
[91]
Tiehuis, A.M.; Vincken, K.L.; van den Berg, E.; Hendrikse, J.; Manschot, S.M.; Mali, W.P.; Kappelle, L.J.; Biessels, G.J. Cerebral perfusion in relation to cognitive function and type 2 diabetes. Diabetologia, 2008, 51(7), 1321-1326.
[http://dx.doi.org/10.1007/s00125-008-1041-9] [PMID: 18488188]
[92]
Musen, G.; Jacobson, A.M.; Bolo, N.R.; Simonson, D.C.; Shenton, M.E.; McCartney, R.L.; Flores, V.L.; Hoogenboom, W.S. Resting-state brain functional connectivity is altered in type 2 diabetes. Diabetes, 2012, 61(9), 2375-2379.
[http://dx.doi.org/10.2337/db11-1669] [PMID: 22664957]
[93]
Xia, W.; Wang, S.; Sun, Z.; Bai, F.; Zhou, Y.; Yang, Y.; Wang, P.; Huang, Y.; Yuan, Y. Altered baseline brain activity in type 2 diabetes: a resting-state fMRI study. Psychoneuroendocrinology, 2013, 38(11), 2493-2501.
[http://dx.doi.org/10.1016/j.psyneuen.2013.05.012] [PMID: 23786881]
[94]
Zhou, X.; Zhang, J.; Chen, Y.; Ma, T.; Wang, Y.; Wang, J.; Zhang, Z. Aggravated cognitive and brain functional impairment in mild cognitive impairment patients with type 2 diabetes: a resting-state functional MRI study. J. Alzheimers Dis., 2014, 41(3), 925-935.
[http://dx.doi.org/10.3233/JAD-132354] [PMID: 24705547]
[95]
De Felice, F.G.; Lourenco, M.V. Brain metabolic stress and neuroinflammation at the basis of cognitive impairment in Alzheimer’s disease. Front. Aging Neurosci., 2015, 7, 94.
[http://dx.doi.org/10.3389/fnagi.2015.00094] [PMID: 26042036]
[96]
Yaffe, K.; Falvey, C.; Hamilton, N.; Schwartz, A.V.; Simonsick, E.M.; Satterfield, S.; Cauley, J.A.; Rosano, C.; Launer, L.J.; Strotmeyer, E.S.; Harris, T.B. Diabetes, glucose control, and 9-year cognitive decline among older adults without dementia. Arch. Neurol., 2012, 69(9), 1170-1175.
[http://dx.doi.org/10.1001/archneurol.2012.1117] [PMID: 22710333]
[97]
Xu, W.L.; von Strauss, E.; Qiu, C.X.; Winblad, B.; Fratiglioni, L. Uncontrolled diabetes increases the risk of Alzheimer’s disease: a population-based cohort study. Diabetologia, 2009, 52(6), 1031-1039.
[http://dx.doi.org/10.1007/s00125-009-1323-x] [PMID: 19280172]
[98]
Altschul, D.M.; Starr, J.M.; Deary, I.J. Cognitive function in early and later life is associated with blood glucose in older individuals: analysis of the Lothian Birth Cohort of 1936. Diabetologia, 2018, 61(9), 1946-1955.
[http://dx.doi.org/10.1007/s00125-018-4645-8] [PMID: 29860628]
[99]
Feinkohl, I.; Keller, M.; Robertson, C.M.; Morling, J.R.; McLachlan, S.; Frier, B.M.; Deary, I.J.; Strachan, M.W.; Price, J.F. Cardiovascular risk factors and cognitive decline in older people with type 2 diabetes. Diabetologia, 2015, 58(7), 1637-1645.
[http://dx.doi.org/10.1007/s00125-015-3581-0] [PMID: 25847351]
[100]
Shorr, R.I.; de Rekeneire, N.; Resnick, H.E.; Yaffe, K.; Somes, G.W.; Kanaya, A.M.; Simonsick, E.M.; Newman, A.B.; Harris, T.B. Glycemia and cognitive function in older adults using glucose-lowering drugs. J. Nutr. Health Aging, 2006, 10(4), 297-301.
[PMID: 16886100]
[101]
Cukierman-Yaffe, T.; Gerstein, H.C.; Williamson, J.D.; Lazar, R.M.; Lovato, L.; Miller, M.E.; Coker, L.H.; Murray, A.; Sullivan, M.D.; Marcovina, S.M.; Launer, L.J. Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) Investigators. Relationship between baseline glycemic control and cognitive function in individuals with type 2 diabetes and other cardiovascular risk factors: the action to control cardiovascular risk in diabetes-memory in diabetes (ACCORD-MIND) trial. Diabetes Care, 2009, 32(2), 221-226.
[http://dx.doi.org/10.2337/dc08-1153] [PMID: 19171735]
[102]
Crane, P.K.; Walker, R.; Hubbard, R.A.; Li, G.; Nathan, D.M.; Zheng, H.; Haneuse, S.; Craft, S.; Montine, T.J.; Kahn, S.E.; McCormick, W.; McCurry, S.M.; Bowen, J.D.; Larson, E.B. Glucose levels and risk of dementia. N. Engl. J. Med., 2013, 369(6), 540-548.
[http://dx.doi.org/10.1056/NEJMoa1215740] [PMID: 23924004]
[103]
Sommerfield, A.J.; Deary, I.J.; Frier, B.M. Acute hyperglycemia alters mood state and impairs cognitive performance in people with type 2 diabetes. Diabetes Care, 2004, 27(10), 2335-2340.
[http://dx.doi.org/10.2337/diacare.27.10.2335] [PMID: 15451897]
[104]
Ryan, C.M.; Freed, M.I.; Rood, J.A.; Cobitz, A.R.; Waterhouse, B.R.; Strachan, M.W. Improving metabolic control leads to better working memory in adults with type 2 diabetes. Diabetes Care, 2006, 29(2), 345-351.
[http://dx.doi.org/10.2337/diacare.29.02.06.dc05-1626] [PMID: 16443885]
[105]
Luchsinger, J.A.; Palmas, W.; Teresi, J.A.; Silver, S.; Kong, J.; Eimicke, J.P.; Weinstock, R.S.; Shea, S. Improved diabetes control in the elderly delays global cognitive decline. J. Nutr. Health Aging, 2011, 15(6), 445-449.
[http://dx.doi.org/10.1007/s12603-011-0057-x] [PMID: 21623465]
[106]
Spauwen, P.J.; van Eupen, M.G.; Köhler, S.; Stehouwer, C.D.; Verhey, F.R.; van der Kallen, C.J.; Sep, S.J.; Koster, A.; Schaper, N.C.; Dagnelie, P.C.; Schalkwijk, C.G.; Schram, M.T.; van Boxtel, M.P. Associations of advanced glycation end-products with cognitive functions in individuals with and without type 2 diabetes: the maastricht study. J. Clin. Endocrinol. Metab., 2015, 100(3), 951-960.
[http://dx.doi.org/10.1210/jc.2014-2754] [PMID: 25459912]
[107]
Whitmer, R.A.; Gunderson, E.P.; Quesenberry, C.P., Jr; Zhou, J.; Yaffe, K. Body mass index in midlife and risk of Alzheimer disease and vascular dementia. Curr. Alzheimer Res., 2007, 4(2), 103-109.
[http://dx.doi.org/10.2174/156720507780362047] [PMID: 17430231]
[108]
Park, H.S.; Park, J.Y.; Yu, R. Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-alpha and IL-6. Diabetes Res. Clin. Pract., 2005, 69(1), 29-35.
[http://dx.doi.org/10.1016/j.diabres.2004.11.007] [PMID: 15955385]
[109]
Kincaid-Smith, P. Hypothesis: obesity and the insulin resistance syndrome play a major role in end-stage renal failure attributed to hypertension and labelled ‘hypertensive nephrosclerosis’. J. Hypertens., 2004, 22(6), 1051-1055.
[http://dx.doi.org/10.1097/00004872-200406000-00001] [PMID: 15167435]
[110]
Matsumoto, H.; Nakao, T.; Okada, T.; Nagaoka, Y.; Iwasawa, H.; Tomaru, R.; Wada, T. Insulin resistance contributes to obesity-related proteinuria. Intern. Med., 2005, 44(6), 548-553.
[http://dx.doi.org/10.2169/internalmedicine.44.548] [PMID: 16020878]
[111]
de Bresser, J.; Reijmer, Y.D.; van den Berg, E.; Breedijk, M.A.; Kappelle, L.J.; Viergever, M.A.; Biessels, G.J. Utrecht Diabetic Encephalopathy Study Group. Microvascular determinants of cognitive decline and brain volume change in elderly patients with type 2 diabetes. Dement. Geriatr. Cogn. Disord., 2010, 30(5), 381-386.
[http://dx.doi.org/10.1159/000321354] [PMID: 20962529]
[112]
Kawamura, T.; Umemura, T.; Umegaki, H.; Imamine, R.; Kawano, N.; Tanaka, C.; Kawai, M.; Minatoguchi, M.; Kusama, M.; Kouchi, Y.; Watarai, A.; Kanai, A.; Nakashima, E.; Hotta, N. Effect of renal impairment on cognitive function during a 3-year follow up in elderly patients with type 2 diabetes: Association with microinflammation. J. Diabetes Investig., 2014, 5(5), 597-605.
[http://dx.doi.org/10.1111/jdi.12190] [PMID: 25411629]
[113]
Umegaki, H.; Iimuro, S.; Shinozaki, T.; Araki, A.; Sakurai, T.; Iijima, K.; Ohashi, Y.; Ito, H. Japanese Elderly Diabetes Intervention Trial Study Group. Risk factors associated with cognitive decline in the elderly with type 2 diabetes: baseline data analysis of the Japanese Elderly Diabetes Intervention Trial. Geriatr. Gerontol. Int., 2012, 12(Suppl. 1), 103-109.
[http://dx.doi.org/10.1111/j.1447-0594.2011.00817.x] [PMID: 22435945]
[114]
Umemura, T.; Kawamura, T.; Umegaki, H.; Kawano, N.; Mashita, S.; Sakakibara, T.; Hotta, N.; Sobue, G. Association of chronic kidney disease and cerebral small vessel disease with cognitive impairment in elderly patients with type 2 diabetes. Dement. Geriatr. Cogn. Disord. Extra, 2013, 3(1), 212-222.
[http://dx.doi.org/10.1159/000351424] [PMID: 23888167]
[115]
Dalkara, T.; Gursoy-Ozdemir, Y.; Yemisci, M. Brain microvascular pericytes in health and disease. Acta Neuropathol., 2011, 122(1), 1-9.
[http://dx.doi.org/10.1007/s00401-011-0847-6] [PMID: 21656168]
[116]
Craft, S.; Cholerton, B.; Baker, L.D. Insulin and Alzheimer’s disease: untangling the web. J. Alzheimers Dis., 2013, 33(Suppl. 1), S263-S275.
[http://dx.doi.org/10.3233/JAD-2012-129042] [PMID: 22936011]
[117]
Su, F.; Shu, H.; Ye, Q.; Wang, Z.; Xie, C.; Yuan, B.; Zhang, Z.; Bai, F. Brain insulin resistance deteriorates cognition by altering the topological features of brain networks. Neuroimage Clin., 2016, 13, 280-287.
[http://dx.doi.org/10.1016/j.nicl.2016.12.009] [PMID: 28050343]
[118]
Ekblad, L.L.; Rinne, J.O.; Puukka, P.; Laine, H.; Ahtiluoto, S.; Sulkava, R.; Viitanen, M.; Jula, A. Insulin resistance predicts cognitive decline: an 11-year follow-up of a nationally representative adult population sample. Diabetes Care, 2017, 40(6), 751-758.
[http://dx.doi.org/10.2337/dc16-2001] [PMID: 28381479]
[119]
Banks, W.A.; Owen, J.B.; Erickson, M.A. Insulin in the brain: there and back again. Pharmacol. Ther., 2012, 136(1), 82-93.
[http://dx.doi.org/10.1016/j.pharmthera.2012.07.006] [PMID: 22820012]
[120]
Talbot, K.; Wang, H.Y.; Kazi, H.; Han, L.Y.; Bakshi, K.P.; Stucky, A.; Fuino, R.L.; Kawaguchi, K.R.; Samoyedny, A.J.; Wilson, R.S.; Arvanitakis, Z.; Schneider, J.A.; Wolf, B.A.; Bennett, D.A.; Trojanowski, J.Q.; Arnold, S.E. Demonstrated brain insulin resistance in Alzheimer’s disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. J. Clin. Invest., 2012, 122(4), 1316-1338.
[http://dx.doi.org/10.1172/JCI59903] [PMID: 22476197]
[121]
Bloemer, J.; Bhattacharya, S.; Amin, R.; Suppiramaniam, V. Impaired insulin signaling and mechanisms of memory loss. Prog. Mol. Biol. Transl. Sci., 2014, 121, 413-449.
[http://dx.doi.org/10.1016/B978-0-12-800101-1.00013-2] [PMID: 24373245]
[122]
Weaver, J.D.; Huang, M.H.; Albert, M.; Harris, T.; Rowe, J.W.; Seeman, T.E. Interleukin-6 and risk of cognitive decline: MacArthur studies of successful aging. Neurology, 2002, 59(3), 371-378.
[http://dx.doi.org/10.1212/WNL.59.3.371] [PMID: 12177370]
[123]
Badawi, A.; Klip, A.; Haddad, P.; Cole, D.E.; Bailo, B.G.; El-Sohemy, A.; Karmali, M. Type 2 diabetes mellitus and inflammation: Prospects for biomarkers of risk and nutritional intervention. Diabetes Metab. Syndr. Obes., 2010, 3, 173-186.
[http://dx.doi.org/10.2147/DMSO.S9089] [PMID: 21437087]
[124]
Yaffe, K.; Lindquist, K.; Penninx, B.W.; Simonsick, E.M.; Pahor, M.; Kritchevsky, S.; Launer, L.; Kuller, L.; Rubin, S.; Harris, T. Inflammatory markers and cognition in well-functioning African-American and white elders. Neurology, 2003, 61(1), 76-80.
[http://dx.doi.org/10.1212/01.WNL.0000073620.42047.D7] [PMID: 12847160]
[125]
Chung, C.C.; Pimentel, D.; Jor’dan, A.J.; Hao, Y.; Milberg, W.; Novak, V. Inflammation-associated declines in cerebral vasoreactivity and cognition in type 2 diabetes. Neurology, 2015, 85(5), 450-458.
[http://dx.doi.org/10.1212/WNL.0000000000001820] [PMID: 26156513]
[126]
Zhao, W.Q.; Townsend, M. Insulin resistance and amyloidogenesis as common molecular foundation for type 2 diabetes and Alzheimer’s disease. Biochim. Biophys. Acta, 2009, 1792(5), 482-496.
[http://dx.doi.org/10.1016/j.bbadis.2008.10.014] [PMID: 19026743]
[127]
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.; McClean, P.L.; Holscher, C.; Arnold, S.E.; Talbot, K.; Klein, W.L.; Munoz, D.P.; Ferreira, S.T.; De Felice, F.G. An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer’s disease- associated Aβ oligomers. J. Clin. Invest., 2012, 122(4), 1339-1353.
[http://dx.doi.org/10.1172/JCI57256] [PMID: 22476196]
[128]
Fei, L.; Yong-Jun, H.; Zhang-Min, M.; Bing, X.; Shuang, W.; Qian-qian, S.; Jun, L. Rosiglitazone attenuates memory impairment in aged rat with diabetes by inhibiting NFkappa B signal pathway activation. Exp. Clin. Endocrinol. Diabetes, 2015, 123(9), 536-542.
[http://dx.doi.org/10.1055/s-0035-1559607] [PMID: 26285068]
[129]
Gemma, C.; Bickford, P.C. Interleukin-1beta and caspase-1: players in the regulation of age-related cognitive dysfunction. Rev. Neurosci., 2007, 18(2), 137-148.
[http://dx.doi.org/10.1515/REVNEURO.2007.18.2.137] [PMID: 17593876]
[130]
Trollor, J.N.; Smith, E.; Agars, E.; Kuan, S.A.; Baune, B.T.; Campbell, L.; Samaras, K.; Crawford, J.; Lux, O.; Kochan, N.A.; Brodaty, H.; Sachdev, P. The association between systemic inflammation and cognitive performance in the elderly: the Sydney Memory and Ageing Study. Age (Dordr.), 2012, 34(5), 1295-1308.
[http://dx.doi.org/10.1007/s11357-011-9301-x] [PMID: 21853262]
[131]
Koyama, A.; O’Brien, J.; Weuve, J.; Blacker, D.; Metti, A.L.; Yaffe, K. The role of peripheral inflammatory markers in dementia and Alzheimer’s disease: a meta-analysis. J. Gerontol. A Biol. Sci. Med. Sci., 2013, 68(4), 433-440.
[http://dx.doi.org/10.1093/gerona/gls187] [PMID: 22982688]
[132]
Harrison, N.A.; Doeller, C.F.; Voon, V.; Burgess, N.; Critchley, H.D. Peripheral inflammation acutely impairs human spatial memory via actions on medial temporal lobe glucose metabolism. Biol. Psychiatry, 2014, 76(7), 585-593.
[http://dx.doi.org/10.1016/j.biopsych.2014.01.005] [PMID: 24534013]
[133]
Gorska-Ciebiada, M.; Saryusz-Wolska, M.; Borkowska, A.; Ciebiada, M.; Loba, J. Serum levels of inflammatory markers in depressed elderly patients with diabetes and mild cognitive impairment. PLoS One, 2015, 10(3) e0120433
[http://dx.doi.org/10.1371/journal.pone.0120433] [PMID: 25793613]
[134]
Akrivos, J.; Ravona-Springer, R.; Schmeidler, J.; LeRoith, D.; Heymann, A.; Preiss, R.; Hoffman, H.; Koifman, K.; Silverman, J.M.; Schnaider Beeri, M. Glycemic control, inflammation, and cognitive function in older patients with type 2 diabetes. Int. J. Geriatr. Psychiatry, 2015, 30(10), 1093-1100.
[http://dx.doi.org/10.1002/gps.4267] [PMID: 25703191]
[135]
Moreira, P.I.; Santos, M.S.; Seiça, R.; Oliveira, C.R. Brain mitochondrial dysfunction as a link between Alzheimer’s disease and diabetes. J. Neurol. Sci., 2007, 257(1-2), 206-214.
[http://dx.doi.org/10.1016/j.jns.2007.01.017] [PMID: 17316694]
[136]
Lee, S.W.; Clemenson, G.D.; Gage, F.H. New neurons in an aged brain. Behav. Brain Res., 2012, 227(2), 497-507.
[http://dx.doi.org/10.1016/j.bbr.2011.10.009] [PMID: 22024433]
[137]
Lang, B.T.; Yan, Y.; Dempsey, R.J.; Vemuganti, R. Impaired neurogenesis in adult type-2 diabetic rats. Brain Res., 2009, 1258, 25-33.
[http://dx.doi.org/10.1016/j.brainres.2008.12.026] [PMID: 19138677]
[138]
Machida, M.; Fujimaki, S.; Hidaka, R.; Asashima, M.; Kuwabara, T. The insulin regulatory network in adult hippocampus and pancreatic endocrine system. Stem Cells Int., 2012, 2012 959737
[http://dx.doi.org/10.1155/2012/959737] [PMID: 22988465]
[139]
Li, Z.G.; Zhang, W.; Grunberger, G.; Sima, A.A. Hippocampal neuronal apoptosis in type 1 diabetes. Brain Res., 2002, 946(2), 221-231.
[http://dx.doi.org/10.1016/S0006-8993(02)02887-1] [PMID: 12137925]
[140]
Guo, Y.J.; Wang, S.H.; Yuan, Y.; Li, F.F.; Ye, K.P.; Huang, Y.; Xia, W.Q.; Zhou, Y. Vulnerability for apoptosis in the hippocampal dentate gyrus of STZ-induced diabetic rats with cognitive impairment. J. Endocrinol. Invest., 2014, 37(1), 87-96.
[http://dx.doi.org/10.1007/s40618-013-0030-0] [PMID: 24464455]
[141]
Nagayach, A.; Patro, N.; Patro, I. Astrocytic and microglial response in experimentally induced diabetic rat brain. Metab. Brain Dis., 2014, 29(3), 747-761.
[http://dx.doi.org/10.1007/s11011-014-9562-z] [PMID: 24833555]
[142]
Farrall, A.J.; Wardlaw, J.M. Blood-brain barrier: ageing and microvascular disease--systematic review and meta-analysis. Neurobiol. Aging, 2009, 30(3), 337-352.
[http://dx.doi.org/10.1016/j.neurobiolaging.2007.07.015] [PMID: 17869382]
[143]
Bell, R.D.; Zlokovic, B.V. Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer’s disease. Acta Neuropathol., 2009, 118(1), 103-113.
[http://dx.doi.org/10.1007/s00401-009-0522-3] [PMID: 19319544]
[144]
Zuloaga, K.L.; Johnson, L.A.; Roese, N.E.; Marzulla, T.; Zhang, W.; Nie, X.; Alkayed, F.N.; Hong, C.; Grafe, M.R.; Pike, M.M.; Raber, J.; Alkayed, N.J. High fat diet-induced diabetes in mice exacerbates cognitive deficit due to chronic hypoperfusion. J. Cereb. Blood Flow Metab., 2016, 36(7), 1257-1270.
[http://dx.doi.org/10.1177/0271678X15616400] [PMID: 26661233]
[145]
Rivera, E.J.; Goldin, A.; Fulmer, N.; Tavares, R.; Wands, J.R.; de la Monte, S.M. Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer’s disease: link to brain reductions in acetylcholine. J. Alzheimers Dis., 2005, 8(3), 247-268.
[http://dx.doi.org/10.3233/JAD-2005-8304] [PMID: 16340083]
[146]
Alrefaie, Z.; Alhayani, A. Vitamin D3 improves decline in cognitive function and cholinergic transmission in prefrontal cortex of streptozotocin-induced diabetic rats. Behav. Brain Res., 2015, 287, 156-162.
[http://dx.doi.org/10.1016/j.bbr.2015.03.050] [PMID: 25835318]
[147]
Beaudry, J.L.; Riddell, M.C. Effects of glucocorticoids and exercise on pancreatic β-cell function and diabetes development. Diabetes Metab. Res. Rev., 2012, 28(7), 560-573.
[http://dx.doi.org/10.1002/dmrr.2310] [PMID: 22556149]
[148]
de Quervain, D.J.; Aerni, A.; Schelling, G.; Roozendaal, B. Glucocorticoids and the regulation of memory in health and disease. Front. Neuroendocrinol., 2009, 30(3), 358-370.
[http://dx.doi.org/10.1016/j.yfrne.2009.03.002] [PMID: 19341764]
[149]
Reynolds, R.M.; Strachan, M.W.; Labad, J.; Lee, A.J.; Frier, B.M.; Fowkes, F.G.; Mitchell, R.; Seckl, J.R.; Deary, I.J.; Walker, B.R.; Price, J.F. Edinburgh Type 2 Diabetes Study Investigators. Morning cortisol levels and cognitive abilities in people with type 2 diabetes: the Edinburgh type 2 diabetes study. Diabetes Care, 2010, 33(4), 714-720.
[http://dx.doi.org/10.2337/dc09-1796] [PMID: 20097784]
[150]
Zhang, L.; Li, M.; Zhan, L.; Lu, X.; Liang, L.; Su, B.; Sui, H.; Gao, Z.; Li, Y.; Liu, Y.; Wu, B.; Liu, Q. Plasma metabolomic profiling of patients with diabetes-associated cognitive decline. PLoS One, 2015, 10(5) e0126952
[http://dx.doi.org/10.1371/journal.pone.0126952] [PMID: 25974350]
[151]
Wang, Y.; Xu, X.Y.; Feng, C.H.; Li, Y.L.; Ge, X.; Zong, G.L.; Wang, Y.B.; Feng, B.; Zhang, P. Patients with type 2 diabetes exhibit cognitive impairment with changes of metabolite concentration in the left hippocampus. Metab. Brain Dis., 2015, 30(4), 1027-1034.
[http://dx.doi.org/10.1007/s11011-015-9670-4] [PMID: 25875132]
[152]
Koekkoek, P.S.; Janssen, J.; Kooistra, M.; van den Berg, E.; Kappelle, L.J.; Biessels, G.J.; Rutten, G.E. Cognitive Impairment in Diabetes: rationale and design protocol of the Cog-ID study. JMIR Res. Protoc., 2015, 4(2) e69
[http://dx.doi.org/10.2196/resprot.4224] [PMID: 26058427]
[153]
van Eersel, M.E.; Joosten, H.; Gansevoort, R.T.; Dullaart, R.P.; Slaets, J.P.; Izaks, G.J. The interaction of age and type 2 diabetes on executive function and memory in persons aged 35 years or older. PLoS One, 2013, 8(12) e82991
[http://dx.doi.org/10.1371/journal.pone.0082991] [PMID: 24367577]
[154]
Joosten, H.; van Eersel, M.E.; Gansevoort, R.T.; Bilo, H.J.; Slaets, J.P.; Izaks, G.J. Cardiovascular risk profile and cognitive function in young, middle-aged, and elderly subjects. Stroke, 2013, 44(6), 1543-1549.
[http://dx.doi.org/10.1161/STROKEAHA.111.000496] [PMID: 23640826]
[155]
Novak, V.; Abduljalil, A.M.; Novak, P.; Robitaille, P.M. High-resolution ultrahigh-field MRI of stroke. Magn. Reson. Imaging, 2005, 23(4), 539-548.
[http://dx.doi.org/10.1016/j.mri.2005.02.010] [PMID: 15919599]
[156]
Kodl, C.T.; Franc, D.T.; Rao, J.P.; Anderson, F.S.; Thomas, W.; Mueller, B.A.; Lim, K.O.; Seaquist, E.R. Diffusion tensor imaging identifies deficits in white matter microstructure in subjects with type 1 diabetes that correlate with reduced neurocognitive function. Diabetes, 2008, 57(11), 3083-3089.
[http://dx.doi.org/10.2337/db08-0724] [PMID: 18694971]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 27
ISSUE: 19
Year: 2020
Page: [3151 - 3167]
Pages: 17
DOI: 10.2174/1871530319666190206225635
Price: $65

Article Metrics

PDF: 25
HTML: 1