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The Role of Insulin Resistance in Age-Related Cognitive Decline and Dementia

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Diabetes and the Brain

Part of the book series: Contemporary Diabetes ((CDI))

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Abstract

The role of insulin in peripheral energy metabolism has been well described, and converging evidence has identified a role for insulin in central nervous system functions. Epidemiological studies support an important relationship between diabetes and other insulin-resistant conditions, and cognitive functioning. For example, diabetes increases the risk for memory loss, and treating diabetes can reverse memory loss. These studies have also identified a reciprocal relationship between insulin resistance and dementia, such that one condition increases the risk for the other. A substantial body of work has explored the role of insulin in regulating brain glucose metabolism, memory function, inflammatory responses, and amyloid concentrations. Knowledge of these relationships has suggested that increasing brain insulin activity may have a beneficial impact on memory and may serve as the basis for novel therapeutic strategies for Alzheimer’s disease. Three such strategies include intranasal administration of insulin, drugs that improve insulin sensitivity, and diet and exercise

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References

  1. Havrankova J, Roth J, Brownstein M. Insulin receptors are widely distributed in the central nervous system of the rat. Nature 1978; 272(5656):827–829.

    Article  PubMed  CAS  Google Scholar 

  2. Havrankova J, Schmechel D, Roth J, Brownstein M. Identification of insulin in rat brain. Proc Natl Acad Sci USA 1978; 75(11):5737–5741.

    Article  PubMed  CAS  Google Scholar 

  3. Watson GS, Craft S. Modulation of memory by insulin and glucose: neuropsychological observations in Alzheimer’s disease. Eur J Pharmacol 2004; 490(1–3):97–113.

    Article  PubMed  CAS  Google Scholar 

  4. Messier C. Glucose improvement of memory: a review. Eur J Pharmacol 2004; 490(1–3):33–57.

    Article  PubMed  CAS  Google Scholar 

  5. Lapp JE. Effects glycemic alterations and noun imagery on the learning of paired associates. J Learn Disabil 1981; 14:35–38.

    Article  PubMed  CAS  Google Scholar 

  6. Magistretti PJ. Brain energy metabolism. In: Squire LR, Bloom FE, McConnell SK, Roberts JL, Spitzer NC, Zigmond MJ, eds. Fundamental Neuroscience 2nd ed. San Diego, CA: Academic Press; 2003:339–360.

    Google Scholar 

  7. Manning CA, Ragozzino ME, Gold PE. Glucose enhancement of memory in patients with probable senile dementia of the Alzheimer’s type. Neurobiol Aging 1993; 14(6):523–528.

    Article  PubMed  CAS  Google Scholar 

  8. 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(4):518–524.

    Article  PubMed  CAS  Google Scholar 

  9. Prevalence of diabetes and impaired fasting glucose in adults––United States, 1999–2000. MMWR. Morb Mortal Wkly Rep 2003; 52 (35): 833–837.

    Google Scholar 

  10. 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(2):174–180.

    Article  PubMed  CAS  Google Scholar 

  11. Meneilly GS, Cheung E, Tessier D, Yakura C, Tuokko H. The effect of improved glycemic control on cognitive functions in the elderly patient with diabetes. J Gerontol 1993; 48(4):M117–M121.

    PubMed  CAS  Google Scholar 

  12. Ryan CM, Geckle M. Why is learning and memory dysfunction in Type 2 diabetes limited to older adults? Diabetes Metab Res Rev 2000; 16(5):308–315.

    Article  PubMed  CAS  Google Scholar 

  13. 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(3):438–445.

    Article  PubMed  CAS  Google Scholar 

  14. Ho L, Qin W, Pompl PN, et al. Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer’s disease. FASEB J 2004; 18(7):902–904.

    PubMed  CAS  Google Scholar 

  15. Luchsinger JA, Tang MX, Shea S, Mayeux R. Hyperinsulinemia and risk of Alzheimer disease. Neurology 2004; 63(7):1187–1192.

    PubMed  Google Scholar 

  16. Vanhanen M, Koivisto K, Kuusisto J, et al. Cognitive function in an elderly population with persistent impaired glucose tolerance. Diabetes Care 1998; 21(3):398–402.

    Article  PubMed  CAS  Google Scholar 

  17. 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(12):1305–1312.

    PubMed  CAS  Google Scholar 

  18. Naor M, Steingruber HJ, Westhoff K, Schottenfeld-Naor Y, Gries AF. Cognitive function in elderly non-insulin-dependent diabetic patients before and after inpatient treatment for metabolic control. J Diabetes Complications 1997; 11(1):40–46.

    Article  PubMed  CAS  Google Scholar 

  19. Ryan CM, Freed MI, Rood JA, Cobitz AR, Waterhouse BR, Strachan MW. Improving metabolic control leads to better working memory in adults with type 2 diabetes. Diabetes Care 2006; 29(2):345–351.

    Article  PubMed  Google Scholar 

  20. 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(4):1256–1262.

    Article  PubMed  CAS  Google Scholar 

  21. Leibson CL, Rocca WA, Hanson VA, et al. The risk of dementia among persons with diabetes mellitus: a population-based cohort study. Ann NY Acad Sci 1997; 826:422–427.

    Article  PubMed  CAS  Google Scholar 

  22. Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM. Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology 1999; 53(9):1937–1942.

    PubMed  CAS  Google Scholar 

  23. 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(11):1960–1965.

    Article  PubMed  CAS  Google Scholar 

  24. 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(4–5):423–438.

    Article  PubMed  CAS  Google Scholar 

  25. Rivera EJ, Goldin A, Fulmer N, Tavares R, Wands JR, de la Monte SM. Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer’s disease: link to brain reductions in acetylcholine. J Alzheimers Dis 2005; 8(3):247–268.

    PubMed  CAS  Google Scholar 

  26. Baskin DG, Figlewicz DP, Woods SC, Porte D, Jr, Dorsa DM. Insulin in the brain. Annu Rev Physiol 1987; 49:335–347.

    Article  PubMed  CAS  Google Scholar 

  27. Unger JW, Livingston JN, Moss AM. Insulin receptors in the central nervous system: localization, signalling mechanisms and functional aspects. Prog Neurobiol 1991; 36(5):343–362.

    Article  PubMed  CAS  Google Scholar 

  28. Abbott MA, Wells DG, Fallon JR. The insulin receptor tyrosine kinase substrate p58/53 and the insulin receptor are components of CNS synapses. J Neurosci 1999; 19(17):7300–7308.

    PubMed  CAS  Google Scholar 

  29. de la Monte SM, Wands JR. Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: relevance to Alzheimer’s disease. J Alzheimers Dis 2005; 7(1):45–61.

    Google Scholar 

  30. Watson GS, Craft S. The role of insulin resistance in the pathogenesis of Alzheimer’s disease: implications for treatment. CNS Drugs 2003; 17(1):27–45.

    Article  PubMed  CAS  Google Scholar 

  31. Craft S, Asthana S, Cook DG, et al. Insulin dose-response effects on memory and plasma amyloid precursor protein in Alzheimer’s disease: interactions with apolipoprotein E genotype. Psychoneuroendocrinology 2003; 28(6):809–822.

    Article  PubMed  CAS  Google Scholar 

  32. 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(12):1135–1140.

    Article  PubMed  CAS  Google Scholar 

  33. Craft S, Asthana S, Schellenberg G, et al. Insulin metabolism in Alzheimer’s disease differs according to apolipoprotein E genotype and gender. Neuroendocrinology 1999; 70(2): 146–152.

    Article  PubMed  CAS  Google Scholar 

  34. Craft S, Newcomer J, Kanne S, et al. Memory improvement following induced hyperinsulinemia in Alzheimer’s disease. Neurobiol Aging 1996; 17(1):123–130.

    Article  PubMed  CAS  Google Scholar 

  35. Park CR, Seeley RJ, Craft S, Woods SC. Intracerebroventricular insulin enhances memory in a passive-avoidance task. Physiol Behav 2000; 68(4):509–514.

    Article  PubMed  CAS  Google Scholar 

  36. Bingham EM, Hopkins D, Smith D, et al. The role of insulin in human brain glucose metabolism: an 18fluoro-deoxyglucose positron emission tomography study. Diabetes 2002; 51(12):3384–3390.

    Article  PubMed  CAS  Google Scholar 

  37. Apelt J, Mehlhorn G, Schliebs R. Insulin-sensitive GLUT4 glucose transporters are colocalized with GLUT3-expressing cells and demonstrate a chemically distinct neuron-specific localization in rat brain. J Neurosci Res 1999; 57(5):693–705.

    Article  PubMed  CAS  Google Scholar 

  38. Doyle P, Cusin I, Rohner-Jeanrenaud F, Jeanrenaud B. Four-day hyperinsulinemia in euglycemic conditions alters local cerebral glucose utilization in specific brain nuclei of freely moving rats. Brain Res 1995; 684(1):47–55.

    Article  PubMed  CAS  Google Scholar 

  39. Marfaing P, Penicaud L, Broer Y, Mraovitch S, Calando Y, Picon L. Effects of hyperinsulinemia on local cerebral insulin binding and glucose utilization in normoglycemic awake rats. Neurosci Lett 1990; 115(2–3):279–285.

    Article  PubMed  CAS  Google Scholar 

  40. Blanchard JG, Duncan PM. Effect of combinations of insulin, glucose and scopolamine on radial arm maze performance. Pharmacol Biochem Behav 1997; 58(1):209–214.

    Article  PubMed  CAS  Google Scholar 

  41. Figlewicz DP, Bentson K, Ocrant I. The effect of insulin on norepinephrine uptake by PC12 cells. Brain Res Bull 1993; 32(4):425–431.

    Article  PubMed  CAS  Google Scholar 

  42. Figlewicz DP, Szot P, Israel PA, Payne C, Dorsa DM. Insulin reduces norepinephrine transporter mRNA in vivo in rat locus coeruleus. Brain Res 1993; 602(1):161–164.

    Article  PubMed  CAS  Google Scholar 

  43. Watson GS, Bernhardt T, Reger MA, et al. Insulin effects on CSF norepinephrine and cognition in Alzheimer’s disease. Neurobiol Aging 2006; 27(1):38–41.

    Article  PubMed  CAS  Google Scholar 

  44. 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; 274(49):34893–34902.

    Article  PubMed  CAS  Google Scholar 

  45. van der Heide LP, Kamal A, Artola A, Gispen WH, Ramakers GM. Insulin modulates hippocampal activity-dependent synaptic plasticity in a N-methyl-d-aspartate receptor and phosphatidyl-inositol-3-kinase-dependent manner. J Neurochem 2005; 94(4):1158–1166.

    Article  CAS  Google Scholar 

  46. Skeberdis VA, Lan J, Zheng X, Zukin RS, Bennett MV. Insulin promotes rapid delivery of N-methyl-D- aspartate receptors to the cell surface by exocytosis. Proc Natl Acad Sci USA 2001; 98(6):3561–3566.

    Article  PubMed  CAS  Google Scholar 

  47. Di Luca M, Ruts L, Gardoni F, Cattabeni F, Biessels GJ, Gispen WH. NMDA receptor subunits are modified transcriptionally and post-translationally in the brain of streptozotocin-diabetic rats. Diabetologia 1999; 42(6):693–701.

    Article  PubMed  CAS  Google Scholar 

  48. Garrido GE, Furuie SS, Buchpiguel CA, et al. Relation between medial temporal atrophy and functional brain activity during memory processing in Alzheimer’s disease: a combined MRI and SPECT study. J Neurol Neurosurg Psychiatry 2002; 73(5):508–516.

    Article  PubMed  CAS  Google Scholar 

  49. Corder EH, Saunders AM, Strittmatter WJ, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 1993; 261(5123):921–923.

    Article  PubMed  CAS  Google Scholar 

  50. Craft S, Peskind E, Schwartz MW, Schellenberg GD, Raskind M, Porte D, Jr. Cerebrospinal fluid and plasma insulin levels in Alzheimer’s disease: relationship to severity of dementia and apolipoprotein E genotype. Neurology 1998; 50(1):164–168.

    PubMed  CAS  Google Scholar 

  51. Reger MA, Watson GS, Frey WH, 2nd, et al. Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype. Neurobiol Aging 2006; 27(3):451–458.

    Article  PubMed  CAS  Google Scholar 

  52. Razay G, Wilcock GK. Hyperinsulinaemia and Alzheimer’s disease. Age Ageing 1994; 23(5):396–399.

    Article  PubMed  CAS  Google Scholar 

  53. Frolich L, Blum-Degen D, Riederer P, Hoyer S. A disturbance in the neuronal insulin receptor signal transduction in sporadic Alzheimer’s disease. Ann NY Acad Sci 1999; 893:290–293.

    Article  PubMed  CAS  Google Scholar 

  54. Steen E, Terry BM, Rivera EJ, et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease––is this type 3 diabetes? J Alzheimers Dis 2005; 7(1):63–80.

    PubMed  CAS  Google Scholar 

  55. Lester-Coll N, Rivera EJ, Soscia SJ, Doiron K, Wands JR, de la Monte SM. Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimer’s disease. J Alzheimers Dis 2006; 9(1):13–33.

    PubMed  CAS  Google Scholar 

  56. Marques M, Kulstad JJ, Savard CE, et al. Peripheral A-beta levels regulate A-beta clearance from the central nervous system. J Alzheimers Dis: in press.

    Google Scholar 

  57. Gasparini L, Gouras GK, Wang R, et al. Stimulation of beta-amyloid precursor protein trafficking by insulin reduces intraneuronal beta-amyloid and requires mitogen-activated protein kinase signaling. J Neurosci 2001; 21(8):2561–2570.

    PubMed  CAS  Google Scholar 

  58. Authier F, Posner BI, Bergeron JJ. Insulin-degrading enzyme. Clin Invest Med 1996; 19(3):149–160.

    PubMed  CAS  Google Scholar 

  59. Sudoh S, Frosch MP, Wolf BA. Differential effects of proteases involved in intracellular degradation of amyloid beta-protein between detergent-soluble and -insoluble pools in CHO-695 cells. Biochemistry (Mosc) 2002; 41(4):1091–1099.

    Article  CAS  Google Scholar 

  60. Zhao L, Teter B, Morihara T, et al. Insulin-degrading enzyme as a downstream target of insulin receptor signaling cascade: implications for Alzheimer’s disease intervention. J Neurosci 2004; 24(49):11120–11126.

    Article  PubMed  CAS  Google Scholar 

  61. Watson GS, Peskind ER, Asthana S, et al. Insulin increases CSF Abeta42 levels in normal older adults. Neurology 2003; 60(12):1899–1903.

    PubMed  CAS  Google Scholar 

  62. Balakrishnan K, Verdile G, Mehta PD, et al. Plasma Abeta42 correlates positively with increased body fat in healthy individuals. J Alzheimers Dis 2005; 8(3):269–282.

    PubMed  CAS  Google Scholar 

  63. Cacquevel M, Lebeurrier N, Cheenne S, Vivien D. Cytokines in neuroinflammation and Alzheimer’s disease. Curr Drug Targets 2004; 5(6):529–534.

    Article  PubMed  CAS  Google Scholar 

  64. Montine TJ, Kaye JA, Montine KS, McFarland L, Morrow JD, Quinn JF. Cerebrospinal fluid abeta42, tau, and f2-isoprostane concentrations in patients with Alzheimer disease, other dementias, and in age-matched controls. Arch Pathol Lab Med 2001; 125(4):510–512.

    PubMed  CAS  Google Scholar 

  65. Tarkowski E, Blennow K, Wallin A, Tarkowski A. Intracerebral production of tumor necrosis factor-alpha, a local neuroprotective agent, in Alzheimer disease and vascular dementia. J Clin Immunol 1999; 19(4):223–230.

    Article  PubMed  CAS  Google Scholar 

  66. Dandona P. Endothelium, inflammation, and diabetes. Curr Diab Rep 2002; 2(4):311–315.

    Article  PubMed  Google Scholar 

  67. Krogh-Madsen R, Plomgaard P, Keller P, Keller C, Pedersen BK. Insulin stimulates interleukin-6 and tumor necrosis factor-alpha gene expression in human subcutaneous adipose tissue. Am J Physiol Endocrinol Metab 2004; 286(2):E234–E238.

    Article  PubMed  CAS  Google Scholar 

  68. Soop M, Duxbury H, Agwunobi AO, et al. Euglycemic hyperinsulinemia augments the cytokine and endocrine responses to endotoxin in humans. Am J Physiol Endocrinol Metab 2002; 282(6):E1276–E1285.

    PubMed  CAS  Google Scholar 

  69. White JA, Manelli AM, Holmberg KH, Van Eldik LJ, Ladu MJ. Differential effects of oligomeric and fibrillar amyloid-beta 1–42 on astrocyte-mediated inflammation. Neurobiol Dis 2005; 18(3):459–465.

    Article  PubMed  CAS  Google Scholar 

  70. Combs CK, Johnson DE, Karlo JC, Cannady SB, Landreth GE. Inflammatory mechanisms in Alzheimer’s disease: inhibition of beta-amyloid-stimulated proinflammatory responses and neurotoxicity by PPARgamma agonists. J Neurosci 2000; 20(2):558–567.

    PubMed  CAS  Google Scholar 

  71. Buxbaum JD, Oishi M, Chen HI, et al. Cholinergic agonists and interleukin 1 regulate processing and secretion of the Alzheimer beta/A4 amyloid protein precursor. Proc Natl Acad Sci USA 1992; 89(21):10075–10078.

    Article  PubMed  CAS  Google Scholar 

  72. Papassotiropoulos A, Hock C, Nitsch RM. Genetics of interleukin 6: implications for Alzheimer’s disease. Neurobiol Aging 2001; 22(6):863–871.

    Article  PubMed  CAS  Google Scholar 

  73. Gustafson D, Rothenberg E, Blennow K, Steen B, Skoog I. An 18-year follow-up of overweight and risk of Alzheimer disease. Arch Intern Med 2003; 163(13):1524–1528.

    Article  PubMed  Google Scholar 

  74. Santomauro AT, Boden G, Silva ME, et al. Overnight lowering of free fatty acids with Acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects. Diabetes 1999; 48(9):1836–1841.

    Article  PubMed  CAS  Google Scholar 

  75. Knowler WC, Pettitt DJ, Saad MF, Bennett PH. Diabetes mellitus in the Pima Indians: incidence, risk factors and pathogenesis. Diabetes Metab Rev. 1990; 6(1):1–27.

    Article  PubMed  CAS  Google Scholar 

  76. Paolisso G, Tataranni PA, Foley JE, Bogardus C, Howard BV, Ravussin E. A high concentration of fasting plasma non-esterified fatty acids is a risk factor for the development of NIDDM. Diabetologia 1995; 38(10):1213–1217.

    Article  PubMed  CAS  Google Scholar 

  77. Craft S. Insulin resistance and Alzheimer’s disease pathogenesis: potential mechanisms and implications for treatment. Curr Alzheimer Res 2007; 4(2):147–152.

    Article  PubMed  CAS  Google Scholar 

  78. Dhillon HS, Carman HM, Zhang D, Scheff SW, Prasad MR. Severity of experimental brain injury on lactate and free fatty acid accumulation and Evans blue extravasation in the rat cortex and hippocampus. J Neurotrauma 1999; 16(6):455–469.

    Article  PubMed  CAS  Google Scholar 

  79. Hillered L, Chan PH. Role of arachidonic acid and other free fatty acids in mitochondrial dysfunction in brain ischemia. J Neurosci Res 1988; 20(4):451–456.

    Article  PubMed  CAS  Google Scholar 

  80. Fishel MA, Watson GS, Montine TJ, et al. Hyperinsulinemia provokes synchronous increases in central inflammation and beta-amyloid in normal adults. Arch Neurol 2005; 62(10):1539–1544.

    Article  PubMed  Google Scholar 

  81. Born J, Lange T, Kern W, McGregor GP, Bickel U, Fehm HL. Sniffing neuropeptides: a transnasal approach to the human brain. Nat Neurosci 2002; 5(6):514–516.

    Article  PubMed  CAS  Google Scholar 

  82. Kern W, Born J, Schreiber H, Fehm HL. Central nervous system effects of intranasally administered insulin during euglycemia in men. Diabetes 1999; 48(3):557–563.

    Article  PubMed  CAS  Google Scholar 

  83. Thorne RG, Pronk GJ, Padmanabhan V, Frey WH, 2nd. Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration. Neuroscience 2004; 127(2):481–496.

    Article  PubMed  CAS  Google Scholar 

  84. Benedict C, Hallschmid M, Hatke A, et al. Intranasal insulin improves memory in humans. Psychoneuroendocrinology 2004; 29(10):1326–1334.

    Article  PubMed  CAS  Google Scholar 

  85. Benedict C, Hallschmid M, Schmitz K, et al. Intranasal insulin improves memory in humans: superiority of insulin aspart. Neuropsychopharmacology 2007; 32(1):239–243.

    Article  PubMed  CAS  Google Scholar 

  86. Benedict C, Kern W, Schultes B, Born J, Hallschmid M. Differential sensitivity of men and women to anorexigenic and memory-improving effects of intranasal insulin. J Clin Endocrinol Metab 2008; 93(4):1339–1344.

    Article  PubMed  CAS  Google Scholar 

  87. Reger MA, Watson GS, Green PS, et al. Intranasal insulin administration dose-dependently modulates verbal memory and plasma amyloid-beta in memory-impaired older adults. J Alzheimers Dis 2008; 13(3):323–331.

    PubMed  CAS  Google Scholar 

  88. Reger MA, Watson GS, Green PS, et al. Intranasal insulin improves cognition and modulates beta-amyloid in early AD. Neurology 2008; 70(6):440–448.

    Article  PubMed  CAS  Google Scholar 

  89. Ferre P. The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity. Diabetes 2004; 53(Suppl 1):S43–S50.

    Article  PubMed  CAS  Google Scholar 

  90. Gurnell M. PPARgamma and metabolism: insights from the study of human genetic variants. Clin Endocrinol (Oxf) 2003; 59(3):267–277.

    Article  CAS  Google Scholar 

  91. Sidhu JS, Cowan D, Kaski JC. The effects of rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, on markers of endothelial cell activation, C-reactive protein, and fibrinogen levels in non-diabetic coronary artery disease patients. J Am Coll Cardiol 2003; 42(10):1757–1763.

    Article  PubMed  CAS  Google Scholar 

  92. Moreno S, Farioli-Vecchioli S, Ceru MP. Immunolocalization of peroxisome proliferator-activated receptors and retinoid X receptors in the adult rat CNS. Neuroscience 2004; 123(1):131–145.

    Article  PubMed  CAS  Google Scholar 

  93. Heneka MT, Klockgether T, Feinstein DL. Peroxisome proliferator-activated receptor-gamma ligands reduce neuronal inducible nitric oxide synthase expression and cell death in vivo. J Neurosci 2000; 20(18):6862–6867.

    PubMed  CAS  Google Scholar 

  94. Kitamura Y, Kakimura J, Matsuoka Y, Nomura Y, Gebicke-Haerter PJ, Taniguchi T. Activators of peroxisome proliferator-activated receptor-gamma (PPARgamma) inhibit inducible nitric oxide synthase expression but increase heme oxygenase-1 expression in rat glial cells. Neurosci Lett 1999; 262(2):129–132.

    Article  PubMed  CAS  Google Scholar 

  95. Uryu S, Harada J, Hisamoto M, Oda T. Troglitazone inhibits both post-glutamate neurotoxicity and low-potassium-induced apoptosis in cerebellar granule neurons. Brain Res 2002; 924(2):229–236.

    Article  PubMed  CAS  Google Scholar 

  96. Dello Russo C, Gavrilyuk V, Weinberg G, et al. Peroxisome proliferator-activated receptor gamma thiazolidinedione agonists increase glucose metabolism in astrocytes. J Biol Chem 2003; 278(8):5828–5836.

    Article  PubMed  CAS  Google Scholar 

  97. Feinstein DL, Spagnolo A, Akar C, et al. Receptor-independent actions of PPAR thiazolidinedione agonists: is mitochondrial function the key? Biochem Pharmacol 2005; 70(2):177–188.

    Article  PubMed  CAS  Google Scholar 

  98. Watson GS, Cholerton BA, Reger MA, et al. 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(11):950–958.

    PubMed  Google Scholar 

  99. Risner ME, Saunders AM, Altman JF, et al. Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer’s disease. Pharmacogenomics J 2006; 6(4):246–254.

    PubMed  CAS  Google Scholar 

  100. Mayeux R, Honig LS, Tang MX, et al. Plasma A[beta]40 and A[beta]42 and Alzheimer’s disease: relation to age, mortality, and risk. Neurology 2003; 61(9):1185–1190.

    PubMed  CAS  Google Scholar 

  101. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346(6):393–403.

    Article  PubMed  CAS  Google Scholar 

  102. Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001; 344(18):1343–1350.

    Article  PubMed  CAS  Google Scholar 

  103. Larson EB, Wang L, Bowen JD, et al. Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann Intern Med 2006; 144(2):73–81.

    PubMed  Google Scholar 

  104. Kim YP, Kim H, Shin MS, et al. Age-dependence of the effect of treadmill exercise on cell proliferation in the dentate gyrus of rats. Neurosci Lett 2004; 355(1–2):152–154.

    Article  PubMed  CAS  Google Scholar 

  105. Trejo JL, Carro E, Torres-Aleman I. Circulating insulin-like growth factor I mediates exercise-induced increases in the number of new neurons in the adult hippocampus. J Neurosci 2001; 21(5):1628–1634.

    PubMed  CAS  Google Scholar 

  106. Kaiyala KJ, Prigeon RL, Kahn SE, Woods SC, Schwartz MW. Obesity induced by a high-fat diet is associated with reduced brain insulin transport in dogs. Diabetes 2000; 49(9):1525–1533.

    Article  PubMed  CAS  Google Scholar 

  107. Wang J, Ho L, Qin W, et al. Caloric restriction attenuates beta-amyloid neuropathology in a mouse model of Alzheimer’s disease. FASEB J. 2005; 19(6):659–661.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, University of Washington, 98108, Seattle, WA, USA

    G. Stennis Watson PhD

  2. Geriatric Research, Education and Clinical Center Veterans Affairs Puget Sound, University of Washington, 98108, Seattle, WA, USA

    Suzanne Craft PhD

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Correspondence to G. Stennis Watson PhD .

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Editors and Affiliations

  1. Dept. Neurology, University Medical Center Utrecht, Utrecht, 3508 GA, Netherlands

    Geert Jan Biessels

  2. Medical Center, Columbia University, West 168th St. 622, New York, 10032, U.S.A.

    Jose A. Luchsinger

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Watson, G.S., Craft, S. (2009). The Role of Insulin Resistance in Age-Related Cognitive Decline and Dementia. In: Biessels, G., Luchsinger, J. (eds) Diabetes and the Brain. Contemporary Diabetes. Humana Press. https://doi.org/10.1007/978-1-60327-850-8_18

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  • DOI: https://doi.org/10.1007/978-1-60327-850-8_18

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