Type 2 Diabetes Mellitus and Cognitive Impairment

Johanda Damanik, Em Yunir


Type 2 diabetes mellitus (T2DM) is strongly associated with lower performance on multiple domains of cognitive function and with structural abnormalities of the brain. With the growing epidemic of diabetes and aging population, neural complications of diabetes are expected to rise and becoming a challenge for future health implications. Understanding pathophysiology, factors associated with this complication, manifestation of cognitive impairment and various metabolic and neuroradiologic markers suggestive of this pathologic condition is crucial for proper management of this potentially debilitating complication of T2DM. This review will discuss briefly important aspects of cognitive impairment in T2DM.


type 2 diabetes mellitus; cognitive impairment


Kandimalla R, Thirumala V, Reddy PH. Is Alzheimer’s disease a type 3 diabetes? A critical appraisal. Biochimica et Biophysica Acta. 2017;1863(5):1078-89. http://dx.doi.org/10.1016/j.bbadis.2016.08.018

Moheet A, Mangia S, Seaquist ER. Impact of diabetes on cognitive function and brain structure. Ann N Y Acad Sci. 2015;1353:60–71. DOI: 10.1111/nyas.12807

Mayeda ER, Haan MN, Kanaya AM, Yaffe K, Neuhaus J. Type 2 diabetes and 10-year risk of dementia and cognitive impairment among older Mexican. Am Diab Care. 2013;36:2600-6. DOI: 10.2337/dc12-2158

Cheng G, Huang C, Deng H, Wang H. Diabetes as a risk factor for dementia and mild cognitive impairment: a meta-analysis of longitudinal studies. Int J Geriatr Psychiatry. 2013;28(5):441–9. http://dx.doi.org/10.2147/CIA.S48926

Kim B, Feldman EL. Insulin resistance as a key link for the increased risk of cognitive impairment in the metabolic syndrome. Experimental & Molecular Medicine.2016;47:e149–10. DOI:10.1038/emm.2015.3

Umegaki H. Type 2 diabetes as a risk factor for cognitive impairment: current insights. Clinical Interventions in Aging. 2014;9:1011–9. http://dx.doi.org/10.2147/CIA.S48926

Morris JK, Vidoni ED, Honea RA, Burns JM. Impaired glycemia increases disease progression in mild cognitive impairment. Neurobiology of Aging. 2014;35(3):585–9. http://dx.doi.org/10.1016/j.neurobiolaging.2013.09.033.

Murray AM, Hsu FC, Williamson JD, et al. Accordion mind: results of the observational extension of the Accord Mind randomisec trial. Diabetologia. 2017; 60(1): 69–80. DOI:10.1007/s00125-016-4118-x

Ryan JP, Fine DF, Rosano C. Type 2 diabetes and cognitive impairment: contributions from neuroimaging. J Ger Psychiatry Neurol. 2014;27(1):47–55. DOI: 10.1177/0891988713516543

De la Monte SM. Relationship between diabetes and cognitive impairment. Endocrinol Metab Clin North Am. 2014;43(1):245–267. DOI:10.1016/j.ecl.2013.09.006.

Biessels GJ, Reagan LP. Hippocampal insulin resistance and cognitive dysfunction. Nature Reviews. 2015;16:660-71. DOI:10.1038/nrn4019

Reijmer YD, Brundel M, De Bresser J, Kappelle LJ, Leemans A, Biessels GJ. Microstructural white matter abnormalities and cognitive functioning in type 2 diabetes: a diffusion tensor imaging study. Diabetes Care. 2013;36(1):137–44. DOI: 10.2337/dc12-0493

Van Den Berg E, Reijmer YD, De Bresser J, Kessels RPC, Kappelle LJ, Biessels GJ. A 4 year follow-up study of cognitive functioning in patients with type 2 diabetes mellitus. Diabetologia. 2010;53(1):58–65. DOI 10.1007/s00125-009-1571-9.

Wennberg AMV, Hagen CE, Gottesman RF, et al. Longitudinal association between diabetes and cognitive decline: The National Health and Aging Trends Study. Arch Gerontol Geriatr. 2017;72:39–44. DOI:10.1016/j.archger.2017.05.005.

Auroprajna P, Naik BM, Sahoo JP, Keerthi GS, Pavanya M, Pal GK. Association of sympathovagal imbalance with cognitive impairment in type 2 diabetes in adults. Can J Diabetes. 2018;42(1):44–50. https://doi.org/10.1016/j.jcjd.2017.01.008

Ebesunun MO, Obajobi EO. Elevated plasma homocysteine in type 2 diabetes mellitus: A risk factor for cardiovascular diseases. Pan Afr Med J. 2012;12(1):1–8.

Masuda Y, Kubo A, Kokaze A, Yoshida M, Fukuhara N, Takashima Y. Factors associated with serum total homocysteine level in type 2 diabetes. Environ Health Prev Med. 2008;13(3):148–55. DOI 10.1007/s12199-008-0024-2

Shaikh MK, Devrajani BR, Shaikh A, Shah SZA, Shaikh S SD. Plasma homocysteine level in patients with diabetes mellitus. World Appl Sci J. 2012;63(6):1158–63. DOI 10.1007/s12199-008-0024-2.

Huang T, Ren JJ, Huang J, Li D. Association of homocysteine with type 2 diabetes: A meta-analysis implementing Mendelian randomization approach. BMC Genomics. 2013;14(1).

Tian S, Han J, Huang R, et al. Increased plasma homocysteine level is associated with executive dysfunction in type 2 diabetic patients with mild cognitive impairment. J Alzheimer’s Dis. 2017;58(4):1163–73. DOI 10.3233/JAD-170162

Zhang Y, Zhang X, Zhang J, et al. Gray matter volume abnormalities in type 2 diabetes mellitus with and without mild cognitive impairment. Neurosci Lett. 2014;562:1–6. http://dx.doi.org/10.1016/j.neulet.2014.01.006

Biessels GJ, Reijmer YD. Brain changes underlying cognitive dysfunction in diabetes: what can we learn from MRI? Diabetes. 2014;63:2244-52. DOI: 10.2337/db14-0348.

Zhang H, Hao Y, Manor B, et al. Intranasal insulin enhanced resting-state functional connectivity of hippocampal regions in type 2 diabetes. Diabetes. 2015;64(3):1025–34. DOI: 10.2337/db14-1000

Novak V, Milberg W, Hao Y, et al. Enhancement of vasoreactivity andcognition by intranasal insulin in Type 2 diabetes. Diabetes Care. 2014;37(3):751–9. DOI: 10.2337/dc13-1672.

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