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Diabetes Mellitus and Its Impact on Sporadic Alzheimer’s Disease

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Studies on Alzheimer's Disease

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Abstract

The prevalence of type 2 diabetes mellitus (T2DM) is increasing, and it affects 338 million people worldwide. Approximately 36 million people worldwide have dementia. Alzheimer’s disease (AD) is the most common form of dementia in elderly people. There is convincing evidence from epidemiology, neuropathology and neuroimaging showing an increased risk of AD in people with T2DM. The possible mechanisms linking T2DM and AD include vascular pathways, hyperglycemia, insulin resistance, inflammation, oxidative stress, and mitochondrial dysfunction as well as genetic factors. T2DM may lead to AD through a mixed pathology invoving both vascual and nonvascular changes in the brain. Among diabetic patients, diabetic treatment may play an imprtant role in the development of AD, and effective glyceamic control may attenuate the risk of AD, while hypoglycemia may increase the risk of dementia. Although T2DM and AD may share common pathological process, the two disorders may not be directly linked. A better understanding of the key mechanisms underlying diabetes and AD is needed for the design of preventive and therapeutic strategies.

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References

  1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2006;29(Suppl 1):S43–48.

    Google Scholar 

  2. American Diabetes Association. Standards of medical care in diabetes – 2006. Diabetes Care. 2006;29(Suppl 1):S4–42.

    Google Scholar 

  3. World Health Organization. Use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus. Geneva: WHO; 2011.

    Google Scholar 

  4. IDF Diabetes Atlas. International Diabetes Federation. 2009. http://www.idf.org/diabetesatlas/downloads/backgroundpapers. Accessed 10 Mar 2013.

  5. Petrica L, Petrica M, Vlad A, et al. Cerebrovascular reactivity is impaired in patients with non-insulin-dependent diabetes mellitus and microangiopathy. Wien Klin Wochenschr. 2007;119:365–71.

    Article  PubMed  Google Scholar 

  6. Smith U, Laakso M, Eliasson B, et al. Pathogenesis and treatment of diabetic vascular disease – illustrated by two cases. J Intern Med. 2006;260:409–20.

    Article  PubMed  CAS  Google Scholar 

  7. Hwang JS, Wu TL, Chou SC, et al. Development of multiple complications in type 2 diabetes is associated with the increase of multiple markers of chronic inflammation. J Clin Lab Anal. 2008;22:6–13.

    Article  PubMed  Google Scholar 

  8. Chanudet X, Bonnevie L, Bauduceau B. Coronary heart disease and cardiovascular autonomic neuropathy in the elderly diabetic. Diabetes Metab. 2007;33 (Suppl 1):S19–31.

    Article  PubMed  Google Scholar 

  9. Gispen WH, Biessels GJ. Cognition and synaptic plasticity in diabetes mellitus. Trends Neurosci. 2000;23:542–9.

    Article  PubMed  CAS  Google Scholar 

  10. Fratiglioni L, Winblad B, von Strauss E. Prevention of Alzheimer’s disease and dementia. Major findings from the Kungsholmen Project. Physiol Behav. 2007;92:98–104.

    Article  PubMed  CAS  Google Scholar 

  11. Roman GC. Vascular dementia: distinguishing characteristics, treatment, and prevention. J Am Geriatr Soc. 2003;51:S296–304.

    Article  PubMed  Google Scholar 

  12. Korczyn AD, Vakhapova V. The prevention of the dementia epidemic. J Neurol Sci. 2007;257:2–4.

    Article  PubMed  Google Scholar 

  13. Qiu C, Kivipelto M, von Strauss E. Epidemiology of Alzheimer’s disease: occurrence, determinants, and strategies toward intervention. Dialogues Clin Neurosci. 2009;11:111–28.

    PubMed  Google Scholar 

  14. Bennett DA, Wilson RS, Schneider JA, et al. Apolipoprotein E epsilon4 allele, AD pathology, and the clinical expression of Alzheimer’s disease. Neurology. 2003;60:246–52.

    Article  PubMed  CAS  Google Scholar 

  15. Arvanitakis Z, Wilson RS, Bennett DA. Diabetes mellitus, dementia, and cognitive function in older persons. J Nutr Health Aging. 2006;10:287–91.

    PubMed  CAS  Google Scholar 

  16. Exalto LG, Whitmer RA, Kappele LJ, et al. An update on type 2 diabetes, vascular dementia and Alzheimer’s disease. Exp Gerontol. 2012;47:858–64.

    Article  PubMed  CAS  Google Scholar 

  17. Cheng G, Huang C, Deng H, et al. Diabetes as a risk factor for dementia and mild cognitive impairment: a meta-analysis of longitudinal studies. Intern Med J. 2012;42:484–91.

    Article  PubMed  CAS  Google Scholar 

  18. Peila R, Rodriguez BL, Launer LJ. Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study. Diabetes. 2002;51:1256–62.

    Article  PubMed  CAS  Google Scholar 

  19. MacKnight C, Rockwood K, Awalt E, et al. Diabetes mellitus and the risk of dementia, Alzheimer’s disease and vascular cognitive impairment in the Canadian Study of Health and Aging. Dement Geriatr Cogn Disord. 2002;14:77–83.

    Article  PubMed  Google Scholar 

  20. Luchsinger JA, Reitz C, Honig LS, et al. Aggregation of vascular risk factors and risk of incident Alzheimer disease. Neurology. 2005;65:545–51.

    Article  PubMed  CAS  Google Scholar 

  21. Arvanitakis Z, Schneider JA, Wilson RS, et al. Diabetes is related to cerebral infarction but not to AD pathology in older persons. Neurology. 2006;67:1960–5.

    Article  PubMed  CAS  Google Scholar 

  22. Ahtiluoto S, Polvikoski T, Peltonen M, et al. Diabetes, Alzheimer disease, and vascular dementia: a population-based neuropathologic study. Neurology. 2010;75:1195–202.

    Article  PubMed  CAS  Google Scholar 

  23. Ohara T, Doi Y, Ninomiya T, et al. Glucose tolerance status and risk of dementia in the community: the Hisayama study. Neurology. 2011;77:1126–34.

    Article  PubMed  CAS  Google Scholar 

  24. Kimm H, Lee PH, Shin YJ, et al. Mid-life and late-life vascular risk factors and dementia in Korean men and women. Arch Gerontol Geriatr. 2011;52:e117–22.

    Article  PubMed  CAS  Google Scholar 

  25. Hassing LB, Johansson B, Nilsson SE, et al. Diabetes mellitus is a risk factor for vascular dementia, but not for Alzheimer’s disease: a population-based study of the oldest old. Int Psychogeriatr. 2002;14:239–48.

    Article  PubMed  Google Scholar 

  26. Akomolafe A, Beiser A, Meigs JB, et al. Diabetes mellitus and risk of developing Alzheimer disease: results from the Framingham Study. Arch Neurol. 2006;63:1551–5.

    Article  PubMed  Google Scholar 

  27. Xu WL, von Strauss E, Qiu CX, et al. Uncontrolled diabetes increases the risk of Alzheimer’s disease: a population-based cohort study. Diabetologia. 2009;52:1031–9.

    Article  PubMed  CAS  Google Scholar 

  28. Raffaitin C, Gin H, Empana JP, et al. Metabolic syndrome and risk for incident Alzheimer’s disease or vascular dementia: the Three-City Study. Diabetes Care. 2009;32:169–74.

    Article  PubMed  Google Scholar 

  29. Irie F, Fitzpatrick AL, Lopez OL, et al. Enhanced risk for Alzheimer disease in persons with type 2 diabetes and APOE epsilon4: the Cardiovascular Health Study Cognition Study. Arch Neurol. 2008;65:89–93.

    Article  PubMed  Google Scholar 

  30. Wang KC, Woung LC, Tsai MT, et al. Risk of Alzheimer’s disease in relation to diabetes: a population-based cohort study. Neuroepidemiology. 2012;38:237–44.

    Article  PubMed  Google Scholar 

  31. Hayden KM, Zandi PP, Lyketsos CG, et al. Vascular risk factors for incident Alzheimer disease and vascular dementia: the Cache County study. Alzheimer Dis Assoc Disord. 2006;20:93–100.

    Article  PubMed  Google Scholar 

  32. Borenstein AR, Wu Y, Mortimer JA, et al. Developmental and vascular risk factors for Alzheimer’s disease. Neurobiol Aging. 2005;26:325–34.

    Article  PubMed  CAS  Google Scholar 

  33. Xu W, Qiu C, Winblad B, et al. The effect of borderline diabetes on the risk of dementia and Alzheimer’s disease. Diabetes. 2007;56:211–6.

    Article  PubMed  CAS  Google Scholar 

  34. Muller M, Tang MX, Schupf N, et al. Metabolic syndrome and dementia risk in a multiethnic elderly cohort. Dement Geriatr Cogn Disord. 2007;24:185–92.

    Article  PubMed  Google Scholar 

  35. Tyas SL, Manfreda J, Strain LA, et al. Risk factors for Alzheimer’s disease: a population-based, longitudinal study in Manitoba, Canada. Int J Epidemiol. 2001;30:590–7.

    Article  PubMed  CAS  Google Scholar 

  36. Xu W, Qiu C, Gatz M, et al. Mid- and late-life diabetes in relation to the risk of dementia: a population-based twin study. Diabetes. 2009;58:71–7.

    Article  PubMed  CAS  Google Scholar 

  37. Becker JT, Chang YF, Lopez OL, et al. Depressed mood is not a risk factor for incident dementia in a community-based cohort. Am J Geriatr Psychiatry. 2009;17:653–63.

    Article  PubMed  Google Scholar 

  38. 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; [Epub ahead of print].

    Google Scholar 

  39. Echavarri C, Burgmans S, Caballero MC, et al. Co-occurrence of different pathologies in dementia: implications for dementia diagnosis. J Alzheimers Dis. 2012;30:909–17.

    PubMed  Google Scholar 

  40. Schneider JA, Arvanitakis Z, Bang W, et al. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology. 2007;69:2197–204.

    Article  PubMed  Google Scholar 

  41. van Harten B, de Leeuw FE, Weinstein HC, et al. Brain imaging in patients with diabetes: a systematic review. Diabetes Care. 2006;29:2539–48.

    Article  PubMed  Google Scholar 

  42. van Harten B, Oosterman JM, Potter van Loon BJ, et al. Brain lesions on MRI in elderly patients with type 2 diabetes mellitus. Eur Neurol. 2007;57:70–4.

    Article  PubMed  Google Scholar 

  43. Hsu JL, Chen YL, Leu JG, et al. Microstructural white matter abnormalities in type 2 diabetes mellitus: a diffusion tensor imaging study. Neuroimage. 2012;59:1098–105.

    Article  PubMed  Google Scholar 

  44. Jongen C, Biessels GJ. Structural brain imaging in diabetes: a methodological perspective. Eur J Pharmacol. 2008;585:208–18.

    Article  PubMed  CAS  Google Scholar 

  45. Korf ES, White LR, Scheltens P, et al. Brain aging in very old men with type 2 diabetes: the honolulu-Asia aging study. Diabetes Care. 2006;29:2268–74.

    Article  PubMed  Google Scholar 

  46. Brundel M, van den Berg E, Reijmer YD, et al. Cerebral haemodynamics, cognition and brain volumes in patients with type 2 diabetes. J Diabetes Complications. 2012;26:205–9.

    Article  PubMed  Google Scholar 

  47. Jack Jr CR. Alzheimer disease: new concepts on its neurobiology and the clinical role imaging will play. Radiology. 2012;263:344–61.

    Article  PubMed  Google Scholar 

  48. Nelson PT, Smith CD, Abner EA, et al. Human cerebral neuropathology of Type 2 diabetes mellitus. Biochim Biophys Acta. 2009;1792:454–69.

    Article  PubMed  CAS  Google Scholar 

  49. Beeri MS, Silverman JM, Davis KL, et al. Type 2 diabetes is negatively associated with Alzheimer’s disease neuropathology. J Gerontol A Biol Sci Med Sci. 2005;60:471–5.

    Article  PubMed  Google Scholar 

  50. Xu WL, Qiu CX, Wahlin A, et al. Diabetes mellitus and risk of dementia in the Kungsholmen project: a 6-year follow-up study. Neurology. 2004;63:1181–6.

    Article  PubMed  CAS  Google Scholar 

  51. Ravona-Springer R, Schnaider-Beeri M. The association of diabetes and dementia and possible implications for nondiabetic populations. Expert Rev Neurother. 2011;11:1609–17.

    Article  PubMed  CAS  Google Scholar 

  52. Biessels GJ, Staekenborg S, Brunner E, et al. Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol. 2006;5:64–74.

    Article  PubMed  Google Scholar 

  53. Moreira PI, Custodio JB, Nunes E, et al. Mitochondria from distinct tissues are differently affected by 17beta-estradiol and tamoxifen. J Steroid Biochem Mol Biol. 2011;123:8–16.

    Article  PubMed  CAS  Google Scholar 

  54. Reijmer YD, Brundel M, de Bresser J, et al. Microstructural white matter abnormalities and cognitive functioning in type 2 diabetes: a diffusion tensor imaging study. Diabetes Care. 2013;36:137–44.

    Article  PubMed  Google Scholar 

  55. Jones A, Kulozik P, Ostertag A, et al. Common pathological processes and transcriptional pathways in Alzheimer’s disease and type 2 diabetes. J Alzheimers Dis. 2009;16:787–808.

    PubMed  Google Scholar 

  56. Cole AR, Astell A, Green C, et al. Molecular connexions between dementia and diabetes. Neurosci Biobehav Rev. 2007;31:1046–63.

    Article  PubMed  CAS  Google Scholar 

  57. Qiu WQ, Folstein MF. Insulin, insulin-degrading enzyme and amyloid-beta peptide in Alzheimer’s disease: review and hypothesis. Neurobiol Aging. 2006;27:190–8.

    Article  PubMed  CAS  Google Scholar 

  58. Accardi G, Caruso C, Colonna-Romano G, et al. Can Alzheimer disease be a form of type 3 diabetes? Rejuvenation Res. 2012;15:217–21.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Weili Xu received grants from the Swedish Council for Working Life and Social Research (FAS2012-0022), the Loo and Hans Ostermans Foundation and the Foundation for Geriatric Diseases at Karolinska Institutet, the Gamla Tjänarinnor Foundation, Demensfonden and the Bertil Stohnes Foundation.

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Authors and Affiliations

  1. Aging Research Center, Karolinska Institutet-Stockholm University, Gävlegatan 16, Stockholm, 113 30, Sweden

    Weili Xu M.D., Ph.D.

  2. Department of Epidemiology and Statistics, Tianjin Medical University, Tianjin, People’s Republic of China

    Weili Xu M.D., Ph.D.

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  1. Weili Xu M.D., Ph.D.
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Correspondence to Weili Xu M.D., Ph.D. .

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Editors and Affiliations

  1. Pharmacology, Temple University, Philadelphia, Pennsylvania, USA

    Domenico Praticὸ

  2. Istituto di Gerontologia e Geriatria, Università degli Studi di Perugia, Perugia, Italy

    Patrizia Mecocci

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Xu, W. (2013). Diabetes Mellitus and Its Impact on Sporadic Alzheimer’s Disease. In: Praticὸ, D., Mecocci, P. (eds) Studies on Alzheimer's Disease. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-598-9_12

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