Current Neurology and Neuroscience Reports

, Volume 7, Issue 5, pp 373–380

Type 2 diabetes and risk of cognitive impairment and dementia



Diabetes is a major public health burden. Even a modest effect of diabetes on cognitive function has significant public health implications. Several lines of mechanistic evidence implicate a role of insulin and glucose metabolism on risk of developing dementia, including Alzheimer’s disease. Population-based studies have shown that those with type 2 diabetes mellitus have an increased risk of cognitive impairment, dementia, and neurodegeneration. There are many mechanisms through which diabetes could increase risk of dementia, including glycemia, insulin resistance, oxidative stress, advanced glycation endproducts, inflammatory cytokines, and microvascular and macrovascular disease. This paper presents a review of the evidence on diabetes and increased risk of dementia and cognitive impairment, a discussion of different possible mechanisms, and remaining gaps in our knowledge.


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References and Recommended Reading

  1. 1.
    World Health Organization: Report of the Expert Committee on Diabetes. Geneva, Switzerland; 1980. Report No.: 646.Google Scholar
  2. 2.
    Resnick HE, Harris MI, Brock DB, Harris TB: American Diabetes Association diabetes diagnostic criteria, advancing age, and cardiovascular disease risk profiles: results from the Third National Health and Nutrition Examination Survey. Diabetes Care 2000, 23:176–180.PubMedCrossRefGoogle Scholar
  3. 3.
    Narayan KM, Gregg EW, Fagot-Campagna A, et al.: Diabetes: a common, growing, serious, costly, and potentially preventable public health problem. Diabetes Res Clin Pract 2000, 50(Suppl 2):77–84.CrossRefGoogle Scholar
  4. 4.
    Zimmet P: The burden of type 2 diabetes: Are we doing enough? Diabetes Metab 2003, 29:6S9–18.PubMedCrossRefGoogle Scholar
  5. 5.
    Harris MI, Flegal KM, Cowie CC, et al.: Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988–1994. Diabetes Care 1998, 21:518–524.PubMedCrossRefGoogle Scholar
  6. 6.
    Hebert LE, Beckett LA, Scherr PA, Evans DA: Annual incidence of Alzheimer disease in the United States projected to the years 2000 through 2050. Alzheimer Dis Assoc Disord 2001, 15:169–173.PubMedCrossRefGoogle Scholar
  7. 7.
    Schulingkamp RJ, Pagano TC, Hung D, Raffa RB: Insulin receptors and insulin action in the brain: review and clinical implications. Neurosci Biobehav Rev 2000, 24:855–872.PubMedCrossRefGoogle Scholar
  8. 8.
    Zhao W, Chen H, Xu H, et al.: Brain insulin receptors and spatial memory. Correlated changes in gene expression, tyrosine phosphorylation, and signaling molecules in the hippocampus of water maze trained rats. J Biol Chem 1999, 74:34893–34902.CrossRefGoogle Scholar
  9. 9.
    Gispen WH, Biessels GJ: Cognition and synaptic plasticity in diabetes mellitus. Trends Neurosci 2000, 23:542–549.PubMedCrossRefGoogle Scholar
  10. 10.
    Zhao WQ, Alkon DL: Role of insulin and insulin receptor in learning and memory. Mol Cell Endocrinol 2001, 177:125–134.PubMedCrossRefGoogle Scholar
  11. 11.
    Zhao WQ, Chen H, Quon MJ, Alkon DL: Insulin and the insulin receptor in experimental models of learning and memory. Eur J Pharmacol 2004, 490:71–81.PubMedCrossRefGoogle Scholar
  12. 12.
    Frolich L, Blum-Degen D, Bernstein HG, et al.: Brain insulin and insulin receptors in aging and sporadic Alzheimer’s disease. J Neural Transm 1998, 105:423–438.PubMedCrossRefGoogle Scholar
  13. 13.
    Hoyer S: Is sporadic Alzheimer disease the brain type of non-insulin dependent diabetes mellitus? A challenging hypothesis. J Neural Transm 1998, 105:415–422.PubMedCrossRefGoogle Scholar
  14. 14.
    Edland SD: Insulin-degrading enzyme, apolipoprotein E, and Alzheimer’s disease. J Mol Neurosci 2004, 23:213–217.PubMedCrossRefGoogle Scholar
  15. 15.
    Farris W, Mansourian S, Chang Y, et al.: 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.PubMedCrossRefGoogle Scholar
  16. 16.
    Farris W, Leissring MA, Hemming ML, et al.: Alternative splicing of human insulin-degrading enzyme yields a novel isoform with a decreased ability to degrade insulin and amyloid beta-protein. Biochemistry 2005, 44:6513–6525.PubMedCrossRefGoogle Scholar
  17. 17.
    Blomqvist ME, Chalmers K, Andreasen N, et al.: Sequence variants of IDE are associated with the extent of beta-amyloid deposition in the Alzheimer’s disease brain. Neurobiol Aging 2005, 26:795–802.PubMedCrossRefGoogle Scholar
  18. 18.
    Vanhanen M, Soininen H: Glucose intolerance, cognitive impairment and Alzheimer’s disease. Curr Opin Neurol 1998, 11:673–677.PubMedCrossRefGoogle Scholar
  19. 19.
    Watson GS, Peskind ER, Asthana S, et al.: Insulin increases CSF Abeta42 levels in normal older adults. Neurology 2003, 60:1899–1903.PubMedGoogle Scholar
  20. 20.
    Watson GS, Craft S: The role of insulin resistance in the pathogenesis of Alzheimer’s disease: implications for treatment. CNS Drugs 2003, 17:27–45.PubMedCrossRefGoogle Scholar
  21. 21.
    Craft S, Peskind E, Schwartz MW, et al.: Cerebrospinal fluid and plasma insulin levels in Alzheimer’s disease: relationship to severity of dementia and apolipoprotein E genotype. Neurology 1998, 50:164–168.PubMedGoogle Scholar
  22. 22.
    Craft S, Watson GS: Insulin and neurodegenerative disease: shared and specific mechanisms. Lancet Neurol 2004, 3:169–178.PubMedCrossRefGoogle Scholar
  23. 23.
    Ott A, Stolk RP, Hofman A, et al.: Association of diabetes mellitus and dementia: the Rotterdam Study. Diabetologia 1996, 39:1392–1397.PubMedCrossRefGoogle Scholar
  24. 24.
    Ott A, Stolk RP, van Harskamp F, et al.: Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology 1999, 53:1937–1942.PubMedGoogle Scholar
  25. 25.
    Munch G, Schinzel R, Loske C, et al.: Alzheimer’s disease: synergistic effects of glucose deficit, oxidative stress and advanced glycation endproducts. J Neural Transm 1998, 105:439–461.PubMedCrossRefGoogle Scholar
  26. 26.
    Brownlee M: Advanced protein glycosylation in diabetes and aging. Annu Rev Med 1995, 46:223–234.PubMedCrossRefGoogle Scholar
  27. 27.
    Brownlee M: Negative consequences of glycation. Metabolism 2000, 49(2 Suppl 1):9–13.PubMedCrossRefGoogle Scholar
  28. 28.
    Singh R, Barden A, Mori T, Beilin L: Advanced glycation end-products: a review. Diabetologia 2001, 44:129–146.PubMedCrossRefGoogle Scholar
  29. 29.
    Heitner J, Dickson D: Diabetics do not have increased Alzheimer-type pathology compared with age-matched control subjects. A retrospective postmortem immunocytochemical and histofluorescent study. Neurology 1997, 49:1306–1311.PubMedGoogle Scholar
  30. 30.
    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, 51:1256–1562.PubMedCrossRefGoogle Scholar
  31. 31.
    Schmidt R, Launer LJ, Nilsson LG, et al.: Magnetic resonance imaging of the brain in diabetes: the Cardiovascular Determinants of Dementia (CASCADE) Study. Diabetes 2004, 53:687–692.PubMedCrossRefGoogle Scholar
  32. 32.
    Biessels GJ, Kappelle AC, Bravenboer B, et al.: Cerebral function in diabetes mellitus. Diabetologia 1994, 37:643–650.PubMedCrossRefGoogle Scholar
  33. 33.
    Kamal A, Biessels GJ, Urban IJ, Gispen WH: Hippocampal synaptic plasticity in streptozotocin-diabetic rats: impairment of long-term potentiation and facilitation of long-term depression. Neuroscience 1999, 90:737–745.PubMedCrossRefGoogle Scholar
  34. 34.
    Magarinos AM, McEwen BS: Experimental diabetes in rats causes hippocampal dendritic and synaptic reorganization and increased glucocorticoid reactivity to stress. Proc Natl Acad Sci U S A 2000, 97:11056–11061.PubMedCrossRefGoogle Scholar
  35. 35.
    Li ZG, Zhang W, Grunberger G, Sima AA: Hippocampal neuronal apoptosis in type 1 diabetes. Brain Res 2002, 946:221–231.PubMedCrossRefGoogle Scholar
  36. 36.
    Whitmer RA, Sidney S, Selby J, et al.: Midlife cardiovascular risk factors and risk of dementia in late life. Neurology 2005, 64:277–281.PubMedGoogle Scholar
  37. 37.
    Bruce DG, Harrington N, Davis WA, Davis TM: Dementia and its associations in type 2 diabetes mellitus: the Fremantle Diabetes Study. Diabetes Res Clin Pract 2001, 53:165–172.PubMedCrossRefGoogle Scholar
  38. 38.
    Curb JD, Rodriguez BL, Abbott RD, et al.: Longitudinal association of vascular and Alzheimer’s dementias, diabetes, and glucose tolerance. Neurology 1999, 52:971–975.PubMedGoogle Scholar
  39. 39.
    Leibson CL, Rocca WA, Hanson VA, et al.: The risk of dementia among persons with diabetes mellitus: a population-based cohort study. Ann N Y Acad Sci 1997, 826:422–427.PubMedCrossRefGoogle Scholar
  40. 40.
    Luchsinger JA, Tang MX, Stern Y, et al.: Diabetes mellitus and risk of Alzheimer’s disease and dementia with stroke in a multiethnic cohort. Am J Epidemiol 2001, 154:635–641.PubMedCrossRefGoogle Scholar
  41. 41.
    Macknight C, Rockwood K, Awalt E, McDowell I: 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.PubMedCrossRefGoogle Scholar
  42. 42.
    Curb JD, Rodriguez BL, Abbott RD, et al.: Longitudinal association of vascular and Alzheimer’s dementias, diabetes, and glucose tolerance. Neurology 1999, 52:971–975.PubMedGoogle Scholar
  43. 43.
    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, 14:239–248.PubMedCrossRefGoogle Scholar
  44. 44.
    Ott A, Stolk RP, Hofman A, et al.: Association of diabetes mellitus and dementia: the Rotterdam Study. Diabetologia 1996, 39:1392–1397.PubMedCrossRefGoogle Scholar
  45. 45.
    Brayne C, Gill C, Huppert FA, et al.: Vascular risks and incident dementia: results from a cohort study of the very old. Dement Geriatr Cogn Disord 1998, 9:175–180.PubMedCrossRefGoogle Scholar
  46. 46.
    Haan MN, Shemanski L, Jagust WJ, et al.: The role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons. JAMA 1999, 282:40–46.PubMedCrossRefGoogle Scholar
  47. 47.
    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, 63:1181–1186.PubMedGoogle Scholar
  48. 48.
    Nielson KA, Nolan JH, Berchtold NC, et al.: Apolipoprotein-E genotyping of diabetic dementia patients: Is diabetes rare in Alzheimer’s disease? J Am Geriatr Soc 1996, 44:897–904.PubMedGoogle Scholar
  49. 49.
    Moroney JT, Tang MX, Berglund L, et al.: Low-density lipoprotein cholesterol and the risk of dementia with stroke. JAMA 1999, 282:254–260.PubMedCrossRefGoogle Scholar
  50. 50.
    Yanagisawa K: Cholesterol and pathological processes in Alzheimer’s disease. J Neurosci Res 2002, 70:361–366.PubMedCrossRefGoogle Scholar
  51. 51.
    Hofman A, Ott A, Breteler MM, et al.: Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer’s disease in the Rotterdam Study. Lancet 1997, 349:151–154.PubMedCrossRefGoogle Scholar
  52. 52.
    Frishman WH: Are antihypertensive agents protective against dementia? A review of clinical and preclinical data. Heart Dis 2002, 4:380–386.PubMedCrossRefGoogle Scholar
  53. 53.
    in’t Veld BA, Ruitenberg A, Hofman A, et al.: Antihypertensive drugs and incidence of dementia: the Rotterdam Study. Neurobiol Aging 2001, 22:407–412.CrossRefGoogle Scholar
  54. 54.
    Skoog I, Lernfelt B, Landahl S, et al.: 15-year longitudinal study of blood pressure and dementia. Lancet 1996, 347:1141–1145.PubMedCrossRefGoogle Scholar
  55. 55.
    Tzourio C, Anderson C, Chapman N, et al.: Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med 2003, 163:1069–1075.PubMedCrossRefGoogle Scholar
  56. 56.
    Elias PK, Elias MF, D’Agostino RB, et al.: NIDDM and blood pressure as risk factors for poor cognitive performance. The Framingham Study. Diabetes Care 1997, 20:1388–1395.PubMedCrossRefGoogle Scholar
  57. 57.
    Hachinski V, Munoz DG: Cerebrovascular pathology in Alzheimer’s disease: cause, effect or epiphenomenon? Ann N Y Acad Sci 1997, 826:1–6.PubMedCrossRefGoogle Scholar
  58. 58.
    Breteler MM, Claus JJ, van Duijn CM, et al.: Epidemiology of Alzheimer’s disease. Epidemiol Rev 1992, 14:59–82.PubMedGoogle Scholar
  59. 59.
    de la Torre JC, Mussivand T: Can disturbed brain microcirculation cause Alzheimer’s disease? Neurol Res 1993, 15:146–153.PubMedGoogle Scholar
  60. 60.
    Wong TY, Klein R, Sharrett AR, et al.: Retinal microvascular abnormalities and cognitive impairment in middle-aged persons: the Atherosclerosis Risk in Communities Study. Stroke 2002, 33:1487–1492.PubMedCrossRefGoogle Scholar
  61. 61.
    Merchant C, Tang MX, Albert S, et al.: The influence of smoking on the risk of Alzheimer’s disease. Neurology 1999, 52:1408–1412.PubMedGoogle Scholar
  62. 62.
    Tyas SL, White LR, Petrovitch H, et al.: Mid-life smoking and late-life dementia: the Honolulu-Asia Aging Study. Neurobiol Aging 2003, 24:589–596.PubMedCrossRefGoogle Scholar
  63. 63.
    Mooradian AD: Central nervous system complications of diabetes mellitus: a perspective from the blood-brain barrier. Brain Res Brain Res Rev 1997, 23:210–218.PubMedCrossRefGoogle Scholar
  64. 64.
    Hachinski V, Munoz D: Vascular factors in cognitive impairment: Where are we now? Ann N Y Acad Sci 2000, 903:1–5.PubMedCrossRefGoogle Scholar
  65. 65.
    Miyakawa T, Uehara Y, Desaki J, et al.: Morphological changes of microvessels in the brain with Alzheimer’s disease. Jpn J Psychiatry Neurol 1988, 42:819–824.PubMedGoogle Scholar
  66. 66.
    Kalaria RN: The blood-brain barrier and cerebral microcirculation in Alzheimer disease. Cerebrovasc Brain Metab Rev 1992, 4:226–260.PubMedGoogle Scholar
  67. 67.
    Farkas E, Luiten PG: Cerebral microvascular pathology in aging and Alzheimer’s disease. Prog Neurobiol 2001, 64:575–611.Google Scholar
  68. 68.
    Moody DM, Brown WR, Challa VR, et al.: Cerebral microvascular alterations in aging, leukoaraiosis, and Alzheimer’s disease. Ann N Y Acad Sci 1997, 826:103–116.PubMedCrossRefGoogle Scholar
  69. 69.
    Kalmijn S, Feskens EJ, Launer LJ, et al.: Glucose intolerance, hyperinsulinaemia and cognitive function in a general population of elderly men. Diabetologia 1995, 38:1096–1102.PubMedGoogle Scholar
  70. 70.
    Kalmijn S, Feskens EJ, Launer LJ, Kromhout D: Cerebrovascular disease, the apolipoprotein e4 allele, and cognitive decline in a community-based study of elderly men. Stroke 1996, 27:2230–2235.PubMedGoogle Scholar
  71. 71.
    Strachan MW, Deary IJ, Ewing FM, Frier BM: Is type II diabetes associated with an increased risk of cognitive dysfunction? A critical review of published studies. Diabetes Care 1997, 20:438–445.PubMedCrossRefGoogle Scholar
  72. 72.
    Stewart R, Liolitsa D: Type 2 diabetes mellitus, cognitive impairment and dementia. Diabet Med 1999, 16:93–112.PubMedCrossRefGoogle Scholar
  73. 73.
    Yaffe K GE: Diabetes Mellitus and Cognition. In Harrison’s Principles of Internal Medicine. Edited by Braunwald E, Fauci AS, Isselbacher KJ, et al.: New York: McGraw-Hill; 2001.Google Scholar
  74. 74.
    Gregg EW, Yaffe K, Cauley JA, et al.: Is diabetes associated with cognitive impairment and cognitive decline among older women? Study of Osteoporotic Fractures Research Group. Arch Intern Med 2000, 160:174–180.PubMedCrossRefGoogle Scholar
  75. 75.
    Kanaya AM, Barrett-Connor E, Gildengorin G, Yaffe K: Change in cognitive function by glucose tolerance status in older adults: a 4-year prospective study of the Rancho Bernardo study cohort. Arch Intern Med 2004, 164:1327–1333.PubMedCrossRefGoogle Scholar
  76. 76.
    Elias PK, Elias MF, D’Agostino RB, et al.: NIDDM and blood pressure as risk factors for poor cognitive performance. The Framingham Study. Diabetes Care 1997, 20:1388–1395.PubMedCrossRefGoogle Scholar
  77. 77.
    Wu JH, Haan MN, Liang J, et al.: Impact of diabetes on cognitive function among older Latinos: a population-based cohort study. J Clin Epidemiol 2003, 56:686–693.PubMedCrossRefGoogle Scholar
  78. 78.
    Hassing LB, Grant MD, Hofer SM, et al.: Type 2 diabetes mellitus contributes to cognitive decline in old age: a longitudinal population-based study. J Int Neuropsychol Soc 2004, 10:599–607.PubMedCrossRefGoogle Scholar
  79. 79.
    Arvanitakis Z, Wilson RS, Bienias JL, et al.: Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol 2004, 61:661–666.PubMedCrossRefGoogle Scholar
  80. 80.
    Yaffe K, Blackwell T, Kanaya AM, et al.: Diabetes, impaired fasting glucose, and development of cognitive impairment in older women. Neurology 2004, 63:658–663.PubMedGoogle Scholar
  81. 81.
    Wu JH, Haan MN, Liang J, et al.: Impact of antidiabetic medications on physical and cognitive functioning of older Mexican Americans with diabetes mellitus: a populationbased cohort study. Ann Epidemiol 2003, 13:369–376.PubMedCrossRefGoogle Scholar
  82. 82.
    Logroscino G, Kang JH, Grodstein F: Prospective study of type 2 diabetes and cognitive decline in women aged 70–81 years. BMJ 2004, 328:5480.CrossRefGoogle Scholar
  83. 83.
    Gavin JR: New classification and diagnostic criteria for diabetes mellitus. Clin Cornerstone 1998, 1:1–12.PubMedCrossRefGoogle Scholar
  84. 84.
    Newcomer JW, Craft S, Hershey T, et al.: Glucocorticoidinduced impairment in declarative memory performance in adult humans. J Neurosci 1994, 14:2047–2053.PubMedGoogle Scholar
  85. 85.
    Messier C, Gagnon M, Knott V: Effect of glucose and peripheral glucose regulation on memory in the elderly. Neurobiol Aging 1997, 18:297–304.PubMedCrossRefGoogle Scholar
  86. 86.
    Messier C, Desrochers A, Gagnon M: Effect of glucose, glucose regulation, and word imagery value on human memory. Behav Neurosci 1999, 113:431–438.PubMedCrossRefGoogle Scholar
  87. 87.
    Messier C, Gagnon M: Glucose regulation and brain aging. J Nutr Health Aging 2000, 4:208–213.PubMedGoogle Scholar
  88. 88.
    Worrall GJ, Chaulk PC, Moulton N: Cognitive function and glycosylated hemoglobin in older patients with type II diabetes. J Diabetes Complications 1996, 10:320–324.PubMedCrossRefGoogle Scholar
  89. 89.
    Naor M, Steingruber HJ, Westhoff K, et al.: Cognitive function in elderly non-insulin-dependent diabetic patients before and after inpatient treatment for metabolic control. J Diabetes Complications 1997, 11:40–46.PubMedCrossRefGoogle Scholar
  90. 90.
    Testa MA, Simonson DC: Health economic benefits and quality of life during improved glycemic control in patients with type 2 diabetes mellitus: a randomized, controlled, double-blind trial. JAMA 1998, 280:1490–1496.PubMedCrossRefGoogle Scholar
  91. 91.
    Gradman TJ, Laws A, Thompson LW, Reaven GM: Verbal learning and/or memory improves with glycemic control in older subjects with non-insulin-dependent diabetes mellitus. J Am Geriatr Soc 1993, 41:1305–1312.PubMedGoogle Scholar
  92. 92.
    Meneilly GS, Cheung E, Tessier D, et al.: The effect of improved glycemic control on cognitive functions in the elderly patient with diabetes. J Gerontol 1993, 48:117–121.Google Scholar
  93. 93.
    Yaffe K, Whitmer RA, Krueger K, et al.: Glycosylated hemoglobin level and development of cognitive impairment or dementia in older women. J Nutr Health Aging 2006, 4:293–295.Google Scholar
  94. 94.
    Enzinger C, Fazekas F, Matthews PM, et al.: Risk factors for progression of brain atrophy in aging: six-year followup of normal subjects. Neurology 2005, 64:1704–1711.PubMedCrossRefGoogle Scholar
  95. 95.
    Kalmijn S, Feskens EJ, Launer LJ, et al.: Glucose intolerance, hyperinsulinaemia and cognitive function in a general population of elderly men. Diabetologia 1995, 38:1096–1102.PubMedGoogle Scholar
  96. 96.
    Kuusisto J, Koivisto K, Mykkanen L, et al.: Essential hypertension and cognitive function. The role of hyperinsulinemia. Hypertension 1993, 22:771–779.PubMedGoogle Scholar
  97. 97.
    Kern W, Peters A, Fruehwald-Schultes B, et al.: Improving influence of insulin on cognitive functions in humans. Neuroendocrinology 2001, 74:270–280.PubMedCrossRefGoogle Scholar
  98. 98.
    Craft S, Asthana S, Newcomer JW, et al.: Enhancement of memory in Alzheimer disease with insulin and somatostatin, but not glucose. Arch Gen Psychiatry 1999, 56:1135–1140.PubMedCrossRefGoogle Scholar
  99. 99.
    Biessels GJ, Kamal A, Ramakers GM, et al.: Place learning and hippocampal synaptic plasticity in streptozotocininduced diabetic rats. Diabetes 1996, 45:1259–1266.PubMedCrossRefGoogle Scholar
  100. 100.
    Lannert H, Hoyer S: Intracerebroventricular administration of streptozotocin causes long-term diminutions in learning and memory abilities and in cerebral energy metabolism in adult rats. Behav Neurosci 1998, 112:1199–1208.PubMedCrossRefGoogle Scholar
  101. 101.
    Biessels GJ, Kamal A, Urban IJ, et al.: Water maze learning and hippocampal synaptic plasticity in streptozotocindiabetic rats: effects of insulin treatment. Brain Res 1998, 800:125–135.PubMedCrossRefGoogle Scholar
  102. 102.
    Festa A, D’Agostino R Jr, Tracy RP, Haffner SM: Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes 2002, 51:1131–1137.PubMedCrossRefGoogle Scholar
  103. 103.
    Barzilay JI, Abraham L, Heckbert SR, et al.: The relation of markers of inflammation to the development of glucose disorders in the elderly: the Cardiovascular Health Study. Diabetes 2001, 50:2384–2389.PubMedCrossRefGoogle Scholar
  104. 104.
    Pradhan AD, Manson JE, Rifai N, et al.: C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 2001, 286:327–334.PubMedCrossRefGoogle Scholar
  105. 105.
    Festa A, D’Agostino R Jr, Howard G, et al.: Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation 2000, 102:42–47.PubMedGoogle Scholar
  106. 106.
    Schmidt R, Schmidt H, Curb JD, et al.: Early inflammation and dementia: a 25-year follow-up of the Honolulu-Asia Aging Study. Ann Neurol 2002, 52:168–174.PubMedCrossRefGoogle Scholar
  107. 107.
    Campbell IL, Abraham CR, Masliah E, et al.: Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6. Proc Natl Acad Sci U S A 1993, 90:10061–10065.PubMedCrossRefGoogle Scholar
  108. 108.
    Weaver JD, Huang MH, Albert M, et al.: Interleukin-6 and risk of cognitive decline: MacArthur studies of successful aging. Neurology 2002, 59:371–378.PubMedGoogle Scholar
  109. 109.
    Yaffe K, Lindquist K, Penninx BW, et al.: Inflammatory markers and cognition in well-functioning African-American and white elders. Neurology 2003, 61:76–80.PubMedGoogle Scholar
  110. 110.
    Yaffe K, Kanaya A, Lindquist K, et al.: The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA 2004, 292:2237–2242.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group LLC 2007

Authors and Affiliations

  1. 1.Kaiser Permanente Division of ResearchEpidemiology Etiology & PreventionOaklandUSA

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