OBJECTIVES: This is a review article that deals with the question of whether type 2 diabetes is a risk factor for the development of Alzheimer's disease. METHODS: We searched the PubMed database and relevant publications were selected for review. The introduction, which describes the possibilities of how type 2 diabetes can affect the development of Alzheimer's disease, is followed by other questions related to this issue: May on the contrary Alzheimer's disease induce type 2 diabetes? What is a relative risk for type 2 diabetes to induce dementia? How type 2 diabetes influence conversion of mild cognitive impairment to Alzheimer's disease? What is the role of antidiabetic medication? Proposition of term "type 3 diabetes" for Alzheimer's disease. RESULTS: Type 2 diabetes mellitus has been shown to increase the risk for cognitive decline and dementia, such as Alzheimer's disease and vascular dementia. Despite extensive research and numerous publications, the mechanisms underlying these associations remain unclear. CONCLUSIONS: Because of similar molecular and cellular features among type 1 and type 2 diabetes and insulin resistance associated with memory deficit and cognitive decline, some researches proposed the term "type 3 diabetes" for Alzheimer's disease.

Faculty of Health Sciences Palacky University in Olomouc Olomouc Czech Republic

Faculty of Medicine Palacky University in Olomouc Olomouc Czech Republic

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Fiore V, De Rosa A, Falasca P, Marci M, Guastamacchia E, Licchelli B, et al. Focus on the correlations between Alzheimer's Disease and Type 2 Diabetes. Endocr Metab Immune Disord Drug Targets. 2019;19(5):571-9.

Biessels GJ, Despa F. Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications. Nat Rev Endocrinol. 2018 Oct;14(10):591-604.

Beeri MS, Bendlin BB. The link between type 2 diabetes and dementia: from biomarkers to treatment. Lancet Diabetes Endocrinol. 2020 Sep;8(9):736-8. PubMed

Hayden MR. Type 2 Diabetes Mellitus increases the risk of late-onset Alzheimer's Disease: ultrastructural remodeling of the neurovascular unit and diabetic gliopathy. Brain Sci. 2019 Sep 29;9(10):262. doi: 10.3390/brainsci9100262. PubMed DOI

Salas IH, De Strooper B. Diabetes and Alzheimer's Disease: a link not as simple as it seems. Neurochem Res. 2019 Jun;44(6):1271-8.

Baglietto-Vargas D, Shi J, Yaeger DM, Ager R, LaFerla FM. Diabetes and Alzheimer's disease crosstalk. Neurosci Biobehav Rev. 2016 May;64:272-87.

Lee HJ, Seo HI, Cha HY, Yang YJ, Kwon SH, Yang SJ. Diabetes and Alzheimer's Disease: mechanisms and nutritional aspects. Clin Nutr Res. 2018 Oct;7(4):229-40.

Pruzin JJ, Nelson PT, Abner EL, Arvanitakis Z. Review: relationship of type 2 diabetes to human brain pathology. Neuropathol Appl Neurobiol. 2018 Jun;44(4):347-62.

Bharadwaj P, Wijesekara N, Liyanapathirana M, Newsholme P, Ittner L, Fraser P, et al. The link between Type 2 Diabetes and neurodegeneration: roles for amyloid-β, amylin, and tau proteins. J Alzheimers Dis. 2017;59(2):421-32. PubMed

Martins RN. Understanding the link between dementia and diabetes. J Alzheimers Dis. 2017;59(2):389-92. PubMed

Vagelatos NT, Eslick GD. Type 2 diabetes as a risk factor for Alzheimer's disease: the confounders, interactions, and neuropathology associated with this relationship. Epidemiol Rev. 2013;35:152-60. PubMed

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. Intern Med J. 2012 May;42(5):484-91.

Gudala K, Bansal D, Schifano F, Bhansali A. Diabetes mellitus and risk of dementia: a meta-analysis of prospective observational studies. J Diabetes Investig. 2013 Nov 27;4(6):640-50. PubMed

Zhang J, Chen C, Hua S, Liao H, Wang M, Xiong Y, et al. An updated meta-analysis of cohort studies: Diabetes and risk of Alzheimer's disease. Diabetes Res Clin Pract. 2017 Feb;124:41-7.

Cooper C, Sommerlad A, Lyketsos CG, Livingston G. Modifiable predictors of dementia in mild cognitive impairment: a systematic review and meta-analysis. Am J Psychiatry. 2015 Apr;172(4):323-34. PubMed

Ma F, Wu T, Miao R, Xiao YY, Zhang W, Huang G. Conversion of mild cognitive impairment to dementia among subjects with diabetes: a population-based study of incidence and risk factors with five years of follow-up. J Alzheimers Dis. 2015;43(4):1441-9. PubMed

Samaras K, Makkar S, Crawford JD, Kochan NA, Wen W, Draper B, et al. Metformin use is associated with slowed cognitive decline and reduced incident dementia in older adults with Type 2 Diabetes: The Sydney memory and ageing study. Diabetes Care. 2020 Nov;43(11):2691-701.

Wium-Andersen IK, Osler M, Jørgensen MB, Rungby J, Wium-Andersen MK. Antidiabetic medication and risk of dementia in patients with type 2 diabetes: a nested case-control study. Eur J Endocrinol. 2019 Nov;181(5):499-507.

Bello-Chavolla OY, Antonio-Villa NE, Vargas-Vázquez A, Ávila-Funes JA, Aguilar-Salinas CA. Pathophysiological mechanisms linking Type 2 Diabetes and dementia: review of evidence from clinical, translational and epidemiological research. Curr Diabetes Rev. 2019;15(6):456-70. PubMed

Kandimalla R, Thirumala V, Reddy PH. Is Alzheimer's disease a Type 3 Diabetes? A critical appraisal. Biochim Biophys Acta Mol Basis Dis. 2017 May;1863(5):1078-89. PubMed

Diniz Pereira J, Gomes Fraga V, Morais Santos AL, Carvalho MDG, Caramelli P, Braga Gomes K. Alzheimer's disease and type 2 diabetes mellitus: a systematic review of proteomic studies. J Neurochem. 2021 Mar;156(6):753-76. PubMed