J Korean Diabetes.  2012 Sep;13(3):140-144.

Effect of Diabetes on Dementia and Its Preventive Strategies

• Kim SK

Abstract

There is considerable evidence that type 2 diabetes and its related conditions increase the risk of dementia, although the associations are stronger for vascular dementia than Alzheimer's disease. In addition to cerebrovascular disease, type 2 diabetes mellitus and dementia share several other pathophysiologic features, including hyperinsulinemia, advanced glycation end-product, inflammation, and amyloid deposition. From a clinical perspective, evidence of a link between type 2 diabetes and dementia would suggest that currently available modalities to prevent or treat type 2 diabetes mellitus might be beneficial in preventing dementia, especially Alzheimer's disease. This review summarizes the existing evidence of a link between type 2 diabetes and dementia and the clinical trials that have investigated the effects of anti-diabetic modalities on cognitive outcomes in patients with type 2 diabetes mellitus or its precursor conditions.

Keyword

Alzheimer disease; Type 2 diabetes mellitus; Vascular dementia

MeSH Terms

Aluminum Hydroxide
Alzheimer Disease
Carbonates
Dementia
Dementia, Vascular
Diabetes Mellitus, Type 2
Humans
Hyperinsulinism
Inflammation
Plaque, Amyloid
Aluminum Hydroxide
Carbonates

Reference

1. Evans DA, Funkenstein HH, Albert MS, Scherr PA, Cook NR, Chown MJ, Hebert LE, Hennekens CH, Taylor JO. Prevalence of Alzheimer's disease in a community population of older persons. Higher than previously reported. JAMA. 1989. 262:2551–2556.

2. Kim DH, Na DL, Yeon BG, Kang Y, Min KB, Lee SH, Lee SS, Lee MR, Pyo OJ, Park CB, Kim S, Bae SS. Prevalence of dementia in the elderly of an urban community in Korea. Korean J Prev Med. 1999. 32:306–316.

3. Suh GH, Kim JK, Yeon BK, Park SK, Yoo KY, Yang BK, Kim YS, Cho MJ. Prevalence and risk factors of dementia and depression in the elderly. J Korean Neuropsychiatr Assoc. 2000. 39:809–824.

4. Kimm H, Lee PH, Shin YJ, Park KS, Jo J, Lee Y, Kang HC, Jee SH. Mid-life and late-life vascular risk factors and dementia in Korean men and women. Arch Gerontol Geriatr. 2011. 52:e117–e122.

5. Vermeer SE, Prins ND, den Heijer T, Hofman A, Koudstaal PJ, Breteler MM. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med. 2003. 348:1215–1222.

6. Schneider JA, Arvanitakis Z, Bang W, Bennett DA. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology. 2007. 69:2197–2204.

7. Sonnen JA, Larson EB, Brickell K, Crane PK, Woltjer R, Montine TJ, Craft S. Different patterns of cerebral injury in dementia with or without diabetes. Arch Neurol. 2009. 66:315–322.

8. Watson GS, Peskind ER, Asthana S, Purganan K, Wait C, Chapman D, Schwartz MW, Plymate S, Craft S. Insulin increases CSF Abeta42 levels in normal older adults. Neurology. 2003. 60:1899–1903.

9. Frolich L, Blum-Degen D, Bernstein HG, Engelsberger S, Humrich J, Laufer S, Muschner D, Thalheimer A, Turk A, Hoyer S, Zochling R, Boissl KW, Jellinger K, Riederer P. Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease. J Neural Transm. 1998. 105:423–438.

10. Farris W, Mansourian S, Chang Y, Lindsley L, Eckman EA, Frosch MP, Eckman CB, Tanzi RE, Selkoe DJ, Guenette S. Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proc Natl Acad Sci U S A. 2003. 100:4162–4167.

11. Park CR. Cognitive effects of insulin in the central nervous system. Neurosci Biobehav Rev. 2001. 25:311–323.

12. Sims-Robinson C, Kim B, Rosko A, Feldman EL. How does diabetes accelerate Alzheimer disease pathology? Nat Rev Neurol. 2010. 6:551–559.

13. Ledesma MD, Bonay P, Colaco C, Avila J. Analysis of microtubule-associated protein tau glycation in paired helical filaments. J Biol Chem. 1994. 269:21614–21619.

14. Deane R, Du Yan S, Submamaryan RK, LaRue B, Jovanovic S, Hogg E, Welch D, Manness L, Lin C, Yu J, Zhu H, Ghiso J, Frangione B, Stern A, Schmidt AM, Armstrong DL, Arnold B, Liliensiek B, Nawroth P, Hofman F, Kindy M, Stern D, Zlokovic B. RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nat Med. 2003. 9:907–913.

15. Donahue JE, Flaherty SL, Johanson CE, Duncan JA 3rd, Silverberg GD, Miller MC, Tavares R, Yang W, Wu Q, Sabo E, Hovanesian V, Stopa EG. RAGE, LRP-1, and amyloid-beta protein in Alzheimer's disease. Acta Neuropathol. 2006. 112:405–415.

16. Tamaki C, Ohtsuki S, Terasaki T. Insulin facilitates the hepatic clearance of plasma amyloid beta-peptide (1 40) by intracellular translocation of low-density lipoprotein receptor-related protein 1 (LRP-1) to the plasma membrane in hepatocytes. Mol Pharmacol. 2007. 72:850–855.

17. Sharma S, Prasanthi RPJ, Schommer E, Feist G, Ghribi O. Hypercholesterolemia-induced Abeta accumulation in rabbit brain is associated with alteration in IGF-1 signaling. Neurobiol Dis. 2008. 32:426–432.

18. Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA. Statins and the risk of dementia. Lancet. 2000. 356:1627–1631.

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

20. Bauduceau B, Doucet J, Bordier L, Garcia C, Dupuy O, Mayaudon H. Hypoglycaemia and dementia in diabetic patients. Diabetes Metab. 2010. 36:Suppl 3. S106–S111.

21. Colcombe S, Kramer AF. Fitness effects on the cognitive function of older adults: a meta-analytic study. Psychol Sci. 2003. 14:125–130.

22. Watson GS, Cholerton BA, Reger MA, Baker LD, Plymate SR, Asthana S, Fishel MA, Kulstad JJ, Green PS, Cook DG, Kahn SE, Keeling ML, Craft S. Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone: a preliminary study. Am J Geriatr Psychiatry. 2005. 13:950–958.

23. Risner ME, Saunders AM, Altman JF, Ormandy GC, Craft S, Foley IM, Zvartau-Hind ME, Hosford DA, Roses AD. Rosiglitazone in Alzheimer's Disease Study Group. Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease. Pharmacogenomics J. 2006. 6:246–254.

24. Belinson H, Lev D, Masliah E, Michaelson DM. Activation of the amyloid cascade in apolipoprotein E4 transgenic mice induces lysosomal activation and neurodegeneration resulting in marked cognitive deficits. J Neurosci. 2008. 28:4690–4701.

25. Chen Y, Zhou K, Wang R, Liu Y, Kwak YD, Ma T, Thompson RC, Zhao Y, Smith L, Gasparini L, Luo Z, Xu H, Liao FF. Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription. Proc Natl Acad Sci U S A. 2009. 106:3907–3912.

26. Benedict C, Frey WH 2nd, Schioth HB, Schultes B, Born J, Hallschmid M. Intranasal insulin as a therapeutic option in the treatment of cognitive impairments. Exp Gerontol. 2011. 46:112–115.

27. Reger MA, Watson GS, Frey WH 2nd, Baker LD, Cholerton B, Keeling ML, Belongia DA, Fishel MA, Plymate SR, Schellenberg GD, Cherrier MM, Craft S. Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype. Neurobiol Aging. 2006. 27:451–458.

28. 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. ACCORD MIND investigators. 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. 2011. 10:969–977.

29. Shea S, Weinstock RS, Teresi JA, Palmas W, Starren J, Cimino JJ, Lai AM, Field L, Morin PC, Goland R, Izquierdo RE, Ebner S, Silver S, Petkova E, Kong J, Eimicke JP. IDEATel Consortium. A randomized trial comparing telemedicine case management with usual care in older, ethnically diverse, medically underserved patients with diabetes mellitus: 5 year results of the IDEATel study. J Am Med Inform Assoc. 2009. 16:446–456.