Skip to main content
SpringerLink
Log in

Epidemiological Evidence of the Relationship Between Diabetes and Dementia

  • Chapter
  • First Online:
Diabetes Mellitus

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1128))

Abstract

Growing epidemiological evidence has suggested that subjects with diabetes mellitus are at an increased risk for the development of dementia. However, the results for the subtypes of dementia are inconsistent. This review examined the risk of dementia in subjects with diabetes mellitus and discusses the possible mechanism underlying this association. Diabetes mellitus is associated with a 1.5- to 2.5-fold greater risk of dementia among community-dwelling elderly people. Notably, diabetes mellitus is a significant risk factor for not only vascular dementia but also Alzheimer’s disease. The mechanisms underlying the association are unclear, but it may be multifactorial in nature, involving factors such as cardiovascular risk factors, glucose toxicity, changes in insulin metabolism, and inflammation. The optimal management of these risk factors in early life may be important to prevent future dementia. Furthermore, novel therapeutic strategies will be needed to prevent or reduce the development of dementia in subjects with diabetes mellitus.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abbatecola AM, Rizzo MR, Barbieri M, Grella R, Arciello A, Laieta MT, Acampora R, Passariello N, Cacciapuoti F, Paolisso G (2006) Postprandial plasma glucose excursions and cognitive functioning in aged type 2 diabetics. Neurology 67:235–240

    Article  CAS  Google Scholar 

  • Alley DE, Crimmins EM, Karlamangla A, Hu P, Seeman TE (2008) Inflammation and rate of cognitive change in high-functioning older adults. J Gerontol A Biol Sci Med Sci 63:50–55

    Article  Google Scholar 

  • Artola A, Kamal A, Ramakers GM, Gardoni F, Di Luca M, Biessels GJ, Cattabeni F, Gispen WH (2002) Synaptic plasticity in the diabetic brain: advanced aging? Prog Brain Res 138:305–314

    Article  CAS  Google Scholar 

  • Biessels GJ, Kamal A, Ramakers GM, Urban IJ, Spruijt BM, Erkelens DW, Gispen WH (1996) Place learning and hippocampal synaptic plasticity in streptozotocin-induced diabetic rats. Diabetes 45:1259–1266

    Article  CAS  Google Scholar 

  • Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P (2006) Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol 5:64–74

    Article  Google Scholar 

  • Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259

    Article  CAS  Google Scholar 

  • Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820

    Article  CAS  Google Scholar 

  • Chatterjee S, Peters SA, Woodward M, Mejia Arango S, Batty GD, Beckett N, Beiser A, Borenstein AR, Crane PK, Haan M, Hassing LB, Hayden KM, Kiyohara Y, Larson EB, Li CY, Ninomiya T, Ohara T, Peters R, Russ TC, Seshadri S, Strand BH, Walker R, Xu W, Huxley RR (2016) Type 2 diabetes as a risk factor for dementia in women compared with men: a pooled analysis of 2.3 million people comprising more than 100,000 cases of dementia. Diabetes Care 39:300–307

    CAS  PubMed  Google Scholar 

  • Convit A, De Leon MJ, Tarshish C, De Santi S, Tsui W, Rusinek H, George A (1997) Specific hippocampal volume reductions in individuals at risk for Alzheimer’s disease. Neurobiol Aging 18:131–138

    Article  CAS  Google Scholar 

  • Craft S, Watson GS (2004) Insulin and neurodegenerative disease: shared and specific mechanisms. Lancet Neurol 3:169–178

    Article  CAS  Google Scholar 

  • Craft S, Peskind E, Schwartz MW, Schellenberg GD, Raskind M, Porte D Jr (1998) Cerebrospinal fluid and plasma insulin levels in Alzheimer’s disease: relationship to severity of dementia and apolipoprotein e genotype. Neurology 50:164–168

    Article  CAS  Google Scholar 

  • de Galan BE, Zoungas S, Chalmers J, Anderson C, Dufouil C, Pillai A, Cooper M, Grobbee DE, Hackett M, Hamet P, Heller SR, Lisheng L, Macmahon S, Mancia G, Neal B, Pan CY, Patel A, Poulter N, Travert F, Woodward M, ADVANCE Collaborative Group (2009) 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 52:2328–2336

    Article  Google Scholar 

  • den Heijer T, Vermeer SE, van Dijk EJ, Prins ND, Koudstaal PJ, Hofman A, Breteler MM (2003) Type 2 diabetes and atrophy of medial temporal lobe structures on brain MRI. Diabetologia 46:1604–1610

    Article  Google Scholar 

  • Doi Y, Kiyohara Y, Kubo M, Ninomiya T, Wakugawa Y, Yonemoto K, Iwase M, Iida M (2005) Elevated c-reactive protein is a predictor of the development of diabetes in a general Japanese population: the Hisayama study. Diabetes Care 28:2497–2500

    Article  CAS  Google Scholar 

  • Doi Y, Ninomiya T, Hata J, Fukuhara M, Yonemoto K, Iwase M, Iida M, Kiyohara Y (2010) Impact of glucose tolerance status on development of ischemic stroke and coronary heart disease in a general Japanese population: the Hisayama study. Stroke 41:203–209

    Article  CAS  Google Scholar 

  • Fanelli CG, Porcellati F, Pampanelli S, Bolli GB (2004) Insulin therapy and hypoglycaemia: the size of the problem. Diabetes Metab Res Rev 20(suppl 2):S32–S42

    Article  CAS  Google Scholar 

  • Fuster-Matanzo A, Llorens-Martín M, Hernández F, Avila J (2013) Role of neuroinflammation in adult neurogenesis and Alzheimer disease: therapeutic approaches. Mediat Inflamm 2013:260925

    Article  Google Scholar 

  • Gispen WH, Biessels GJ (2000) Cognition and synaptic plasticity in diabetes mellitus. Trends Neurosci 23:542–549

    Article  CAS  Google Scholar 

  • Gosche KM, Mortimer JA, Smith CD, Markesbery WR, Snowdon DA (2002) Hippocampal volume as an index of Alzheimer neuropathology: findings from the Nun study. Neurology 58:1476–1482

    Article  CAS  Google Scholar 

  • Hata J, Ninomiya T, Hirakawa Y, Nagata M, Mukai N, Gotoh S, Fukuhara M, Ikeda F, Shikata K, Yoshida D, Yonemoto K, Kamouchi M, Kitazono T, Kiyohara Y (2013) Secular trends in cardiovascular disease and its risk factors in Japanese: half-century data from the Hisayama study (1961–2009). Circulation 128:1198–1205

    Article  Google Scholar 

  • Hirabayashi N, Hata J, Ohara T, Mukai N, Nagata M, Shibata M, Gotoh S, Furuta Y, Yamashita F, Yoshihara K, Kitazono T, Sudo N, Kiyohara Y, Ninomiya T (2016) Association between diabetes and hippocampal atrophy in elderly Japanese: the Hisayama study. Diabetes Care 39:1543–14549

    Article  Google Scholar 

  • Jacobson AM, Musen G, Ryan CM, Silvers N, Cleary P, Waberski B, Burwood A, Weinger K, Bayless M, Dahms W, Harth J, Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study Research Group (2007) Long-term effect of diabetes and its treatment on cognitive function. N Engl J Med 356:1842–1852

    Article  Google Scholar 

  • Kalmijn S, Foley D, White L, Burchfiel CM, Curb JD, Petrovitch H, Ross GW, Havlik RJ, Launer LJ (2000) Metabolic cardiovascular syndrome and risk of dementia in Japanese-American elderly men. The Honolulu-Asia Aging Study. Arterioscler Thromb Vasc Biol 20:2255–2260

    Article  CAS  Google Scholar 

  • Krasuski JS, Alexander GE, Horwitz B, Daly EM, Murphy DG, Rapoport SI, Schapiro MB (1998) Volumes of medial temporal lobe structures in patients with Alzheimer’s disease and mild cognitive impairment (and in healthy controls). Biol Psychiatry 43:60–68

    Article  CAS  Google Scholar 

  • Launer LJ, Miller ME, Williamson JD, Lazar RM, Gerstein HC, Murray AM, Sullivan M, Horowitz KR, Ding J, Marcovina S, Lovato LC, Lovato J, Margolis KL, O’Connor P, Lipkin EW, Hirsch J, Coker L, Maldjian J, Sunshine JL, Truwit C, Davatzikos C, Bryan RN (2011) Effects of intensive glucose lowering on brain structure and function in people with type 2 diabetes (ACCORD-MIND): a randomised open-label substudy. Lancet Neurol 10:969–977

    Article  Google Scholar 

  • Lee CC, Adler AI, Sandhu MS, Sharp SJ, Forouhi NG, Erqou S, Luben R, Bingham S, Khaw KT, Wareham NJ (2009) Association of c-reactive protein with type 2 diabetes: prospective analysis and meta-analysis. Diabetologia 52:1040–1047

    Article  CAS  Google Scholar 

  • Lin CH, Sheu WH (2013) Hypoglycaemic episodes and risk of dementia in diabetes mellitus: 7-year follow-up study. J Intern Med 273:102–110

    Article  Google Scholar 

  • Lu FP, Lin KP, Kuo HK (2009) Diabetes and the risk of multi-system aging phenotypes: a systematic review and meta-analysis. PLoS One 4:e4144

    Article  Google Scholar 

  • Mankovsky BN, Ziegler D (2004) Stroke in patients with diabetes mellitus. Diabetes Metab Res Rev 20:268–287

    Article  Google Scholar 

  • Marioni RE, Strachan MW, Reynolds RM, Lowe GD, Mitchell RJ, Fowkes FG, Frier BM, Lee AJ, Butcher I, Rumley A, Murray GD, Deary IJ, Price JF (2010) Association between raised inflammatory markers and cognitive decline in elderly people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study. Diabetes 59:710–713

    Article  CAS  Google Scholar 

  • Matsuzaki T, Sasaki K, Tanizaki Y, Hata J, Fujimi K, Matsui Y, Sekita A, Suzuki SO, Kanba S, Kiyohara Y, Iwaki T (2010) Insulin resistance is associated with the pathology of Alzheimer disease: the Hisayama study. Neurology 75:764–770

    Article  CAS  Google Scholar 

  • McGuinness B, Craig D, Bullock R, Passmore P (2009a) Statins for the prevention of dementia. Cochrane Database Syst Rev 15(2):CD003160

    Google Scholar 

  • McGuinness B, Todd S, Passmore P, Bullock R (2009b) Blood pressure lowering in patients without prior cerebrovascular disease for prevention of cognitive impairment and dementia. Cochrane Database Syst Rev 4:CD004034

    Google Scholar 

  • Moloney AM, Griffin RJ, Timmons S, O’Connor R, Ravid R, O’Neill C (2010) Defects in IGF-1 receptor, insulin receptor and IRS-1/2 in Alzheimer’s disease indicate possible resistance to IGF-1 and insulin signaling. Neurobiol Aging 31:224–243

    Article  CAS  Google Scholar 

  • Nesto R (2004) C-reactive protein, its role in inflammation, type 2 diabetes and cardiovascular disease, and the effects of insulin-sensitizing treatment with thiazolidinediones. Diabet Med 21:810–817

    Article  CAS  Google Scholar 

  • Ninomiya T (2014) Diabetes mellitus and dementia. Curr Diabetes Rep 14:487

    Article  Google Scholar 

  • Ninomiya T, Ohara T, Hirakawa Y, Yoshida D, Doi Y, Hata J, Kanba S, Iwaki T, Kiyohara Y (2011) Midlife and late-life blood pressure and dementia in Japanese elderly: the Hisayama study. Hypertension 58:22–28

    Article  CAS  Google Scholar 

  • Ohara T, Doi Y, Ninomiya T, Hirakawa Y, Hata J, Iwaki T, Kanba S, Kiyohara Y (2011) Glucose tolerance status and risk of dementia in the community: the Hisayama study. Neurology 77:1126–1134

    Article  CAS  Google Scholar 

  • Ohara T, Hata J, Yoshida D, Mukai N, Nagata M, Iwaki T, Kitazono T, Kanba S, Kiyohara Y, Ninomiya T (2017) Trends in dementia prevalence, incidence, and survival rate in a Japanese community. Neurology 88:1925–1932

    Article  Google Scholar 

  • Peila R, Rodriguez BL, Launer LJ (2002) Type 2 diabetes, apoe gene, and the risk for dementia and related pathologies: the Honolulu-Asia Aging Study. Diabetes 51:1256–1262

    Article  CAS  Google Scholar 

  • Qiu C, Winblad B, Fratiglioni L (2005) The age-dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol 4:487–499

    Article  Google Scholar 

  • Risso A, Mercuri F, Quagliaro L, Damante G, Ceriello A (2001) Intermittent high glucose enhances apoptosis in human umbilical vein endothelial cells in culture. Am J Physiol Endocrinol Metab 281:E924–E930

    Article  CAS  Google Scholar 

  • Rizzo MR, Marfella R, Barbieri M, Boccardi V, Vestini F, Lettieri B, Canonico S, Paolisso G (2010) Relationships between daily acute glucose fluctuations and cognitive performance among aged type 2 diabetic patients. Diabetes Care 33:2169–2174

    Article  Google Scholar 

  • Rogers J, Mastroeni D, Leonard B, Joyce J, Grover A (2007) Neuroinflammation in Alzheimer’s disease and Parkinson’s disease: are microglia pathogenic in either disorder? Int Rev Neurobiol 82:235–246

    Article  CAS  Google Scholar 

  • Salkovic-Petrisic M, Osmanovic J, Grünblatt E, Riederer P, Hoyer S (2009) Modeling sporadic Alzheimer’s disease: the insulin resistant brain state generates multiple long-term morphobiological abnormalities including hyperphosphorylated tau protein and amyloid-beta. J Alzheimers Dis 18:729–750

    Article  CAS  Google Scholar 

  • Schmidt MI, Duncan BB, Sharrett AR, Lindberg G, Savage PJ, Offenbacher S, Azambuja MI, Tracy RP, Heiss G (1999) Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk In Communities Study): a cohort study. Lancet 353:1649–1652

    Article  CAS  Google Scholar 

  • Schneider JA, Arvanitakis Z, Leurgans SE, Bennett DA (2009) The neuropathology of probable Alzheimer disease and mild cognitive impairment. Ann Neurol 66:200–208

    Article  Google Scholar 

  • Schott JM, Fox NC, Frost C, Scahill RI, Janssen JC, Chan D, Jenkins R, Rossor MN (2003) Assessing the onset of structural change in familial Alzheimer’s disease. Ann Neurol 53:181–188

    Article  Google Scholar 

  • Schram MT, Euser SM, de Craen AJ, Witteman JC, Frolich M, Hofman A, Jolles J, Breteler MM, Westendorp RG (2007) Systemic markers of inflammation and cognitive decline in old age. J Am Geriatr Soc 55:708–716

    Article  Google Scholar 

  • Serlin Y, Levy J, Shalev H (2011) Vascular pathology and blood-brain barrier disruption in cognitive and psychiatric complications of type 2 diabetes mellitus. Cardiovasc Psychiatry Neurol 2011:609202

    Article  Google Scholar 

  • Sommerfield AJ, Deary IJ, Frier BM (2004) Acute hyperglycemia alters mood state and impairs cognitive performance in people with type 2 diabetes. Diabetes Care 27:2335–2340

    Article  Google Scholar 

  • Thacker EL, Psaty BM, McKnight B, Heckbert SR, Longstreth WT Jr, Mukamal KJ, Meigs JB, de Boer IH, Boyko EJ, Carnethon MR, Kizer JR, Tracy RP, Smith NL, Siscovick DS (2011) Fasting and post-glucose load measures of insulin resistance and risk of ischemic stroke in older adults. Stroke 42:3347–3351

    Article  CAS  Google Scholar 

  • The IDF diabetes atlas (2012) 5th edn. http://www.Idf.Org/diabetesatlas/5e/diabetes

  • The World Alzheimer Report (2015) The global impact of dementia https://www.alz.co.uk/research/WorldAlzheimerReport2015.pdf

  • Tzourio C, Anderson C, Chapman N, Woodward M, Neal B, MacMahon S, Chalmers J (2003) Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med 163:1069–1075

    Article  CAS  Google Scholar 

  • Whitmer RA, Sidney S, Selby J, Johnston SC, Yaffe K (2005) Midlife cardiovascular risk factors and risk of dementia in late life. Neurology 64:277–281

    Article  CAS  Google Scholar 

  • Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP Jr, Selby JV (2009) Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA 301:1565–1572

    Article  CAS  Google Scholar 

  • Wimo A, Guerchet M, Ali GC, Wu YT, Prina AM, Winblad B, Jönsson L, Liu Z, Prince M (2017) The worldwide costs of dementia 2015 and comparisons with 2010. Alzheimers Dement 13:1–7

    Article  Google Scholar 

  • Wright RJ, Frier BM (2008) Vascular disease and diabetes: is hypoglycaemia an aggravating factor? Diabetes Metab Res Rev 24:353–363

    Article  CAS  Google Scholar 

  • Xia MQ, Hyman BT (1999) Chemokines/chemokine receptors in the central nervous system and Alzheimer’s disease. J Neurovirol 5:32–41

    Article  CAS  Google Scholar 

  • Zemva J, Schubert M (2011) Central insulin and insulin-like growth factor-1 signaling: implications for diabetes associated dementia. Curr Diabetes Rev 7:356–366

    Article  CAS  Google Scholar 

  • Zhao WQ, Alkon DL (2001) Role of insulin and insulin receptor in learning and memory. Mol Cell Endocrinol 177:125–134

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Toshiharu Ninomiya

Authors
  1. Toshiharu Ninomiya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Toshiharu Ninomiya .

Editor information

Editors and Affiliations

  1. Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

    Yusaku Nakabeppu

  2. Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Toshiharu Ninomiya

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Ninomiya, T. (2019). Epidemiological Evidence of the Relationship Between Diabetes and Dementia. In: Nakabeppu, Y., Ninomiya, T. (eds) Diabetes Mellitus. Advances in Experimental Medicine and Biology, vol 1128. Springer, Singapore. https://doi.org/10.1007/978-981-13-3540-2_2

Download citation

Publish with us

Policies and ethics

Search

Navigation