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From the Departments of Epidemiology & Biostatistics (Drs. Ott, Stolk, Hofman, and Breteler), Medical Microbiology (Dr. Ott), Neurology (Dr. van Harskamp), and Internal Medicine III, Erasmus University Medical School (Dr. Pols), Rotterdam; and Julius Centre for Patient Oriented Research (Dr. Stolk), Utrecht University, Utrecht, the Netherlands.
Address correspondence and reprint requests to Dr. Alewijn Ott, Department of Epidemiology & Biostatistics, Erasmus University Medical School, PO Box 1738, 3000 DR Rotterdam, the Netherlands.
OBJECTIVE: To determine the influence of type 2 diabetes mellitus on the risk of dementia and AD.
BACKGROUND: Both dementia and diabetes are frequent disorders in elderly people.
METHODS: Prospective population-based cohort study among 6,370 elderly subjects. At baseline study participants were examined for presence of diabetes mellitus. Nondemented participants were followed up, on average, for 2.1 years. Incident dementia was diagnosed using a three-step screening and comprehensive diagnostic workup. To complete the follow-up, medical files were studied of persons who could not be reexamined. We estimated relative risks with proportional hazard regression, adjusting for age, sex, and possible confounders.
RESULTS: During the follow-up, 126 patients became demented, of whom 89 had AD. Diabetes mellitus almost doubled the risk of dementia (relative risk [RR] 1.9 [1.3 to 2.8]) and AD (RR 1.9 [1.2 to 3.1]). Patients treated with insulin were at highest risk of dementia (RR 4.3 [1.7 to 10.5]).
CONCLUSION: The diabetes attributable risk for dementia of 8.8% suggests that diabetes may have contributed to the clinical syndrome in a substantial proportion of all dementia patients.
Key words: AD—Dementia—Diabetes mellitus—Epidemiology—Incidence.
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J. Janson, T. Laedtke, J. E. Parisi, P. O'Brien, R. C. Petersen, and P. C. Butler Increased Risk of Type 2 Diabetes in Alzheimer Disease Diabetes, February 1, 2004; 53(2): 474 - 481. [Abstract] [Full Text]
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M. Schubert, D. P. Brazil, D. J. Burks, J. A. Kushner, J. Ye, C. L. Flint, J. Farhang-Fallah, P. Dikkes, X. M. Warot, C. Rio, et al. Insulin Receptor Substrate-2 Deficiency Impairs Brain Growth and Promotes Tau Phosphorylation J. Neurosci., August 6, 2003; 23(18): 7084 - 7092. [Abstract] [Full Text] [PDF]
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 E. W. Gregg and A. Brown Cognitive and Physical Disabilities and Aging-Related Complications of Diabetes Clin. Diabetes, July 1, 2003; 21(3): 113 - 118. [Abstract] [Full Text] [PDF]
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C. E. Greenwood, R. J. Kaplan, S. Hebblethwaite, and D. J.A. Jenkins Carbohydrate-Induced Memory Impairment in Adults With Type 2 Diabetes Diabetes Care, July 1, 2003; 26(7): 1961 - 1966. [Abstract] [Full Text] [PDF]
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D. Galasko Insulin and Alzheimer's disease: An amyloid connection Neurology, June 24, 2003; 60(12): 1886 - 1887. [Full Text] [PDF]
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P. I. Moreira, M. S. Santos, A. M. Moreno, R. Seica, and C. R. Oliveira Increased Vulnerability of Brain Mitochondria in Diabetic (Goto-Kakizaki) Rats With Aging and Amyloid-{beta} Exposure Diabetes, June 1, 2003; 52(6): 1449 - 1456. [Abstract] [Full Text] [PDF]
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W. Farris, S. Mansourian, Y. Chang, L. Lindsley, E. A. Eckman, M. P. Frosch, C. B. Eckman, R. E. Tanzi, D. J. Selkoe, and S. Guenette Insulin-degrading enzyme regulates the levels of insulin, amyloid beta -protein, and the beta -amyloid precursor protein intracellular domain in vivo PNAS, April 1, 2003; 100(7): 4162 - 4167. [Abstract] [Full Text] [PDF]
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J.M. Wardlaw, P.A.G. Sandercock, M.S. Dennis, J. Starr, and H. Kalimo Is Breakdown of the Blood-Brain Barrier Responsible for Lacunar Stroke, Leukoaraiosis, and Dementia? Stroke, March 1, 2003; 34(3): 806 - 812. [Abstract] [Full Text] [PDF]
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J M Starr, J Wardlaw, K Ferguson, A MacLullich, I J Deary, and I Marshall Increased blood-brain barrier permeability in type II diabetes demonstrated by gadolinium magnetic resonance imaging J. Neurol. Neurosurg. Psychiatry, January 1, 2003; 74(1): 70 - 76. [Abstract] [Full Text] [PDF]
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D. G. Cook, J. B. Leverenz, P. J. McMillan, J. J. Kulstad, S. Ericksen, R. A. Roth, G. D. Schellenberg, L.-W. Jin, K. S. Kovacina, and S. Craft Reduced Hippocampal Insulin-Degrading Enzyme in Late-Onset Alzheimer's Disease Is Associated with the Apolipoprotein E-{epsilon}4 Allele Am. J. Pathol., January 1, 2003; 162(1): 313 - 319. [Abstract] [Full Text] [PDF]
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M. J. Engelhart, M. I. Geerlings, A. Ruitenberg, J. C. van Swieten, A. Hofman, J. C.M. Witteman, and M. M.B. Breteler Diet and risk of dementia: Does fat matter?: The Rotterdam Study Neurology, December 24, 2002; 59(12): 1915 - 1921. [Abstract] [Full Text] [PDF]
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D Liolitsa, J Powell, and S Lovestone Genetic variability in the insulin signalling pathway may contribute to the risk of late onset Alzheimer's disease J. Neurol. Neurosurg. Psychiatry, September 1, 2002; 73(3): 261 - 266. [Abstract] [Full Text] [PDF]
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F M Nilsson, L V Kessing, T M Sorensen, P K Andersen, and T G Bolwig Enduring increased risk of developing depression and mania in patients with dementia J. Neurol. Neurosurg. Psychiatry, July 1, 2002; 73(1): 40 - 44. [Abstract] [Full Text] [PDF]
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 K. Asimakopoulou and S. E. Hampson Cognitive Functioning and Self-Management in Older People With Diabetes Diabetes Spectr, April 1, 2002; 15(2): 116 - 121. [Abstract] [Full Text] [PDF]
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R. Peila, B. L. Rodriguez, and L. J. Launer Type 2 Diabetes, APOE Gene, and the Risk for Dementia and Related Pathologies: The Honolulu-Asia Aging Study Diabetes, April 1, 2002; 51(4): 1256 - 1262. [Abstract] [Full Text] [PDF]
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 T. Perry, D. K. Lahiri, D. Chen, J. Zhou, K. T. Y. Shaw, J. M. Egan, and N. H. Greig A Novel Neurotrophic Property of Glucagon-Like Peptide 1: A Promoter of Nerve Growth Factor-Mediated Differentiation in PC12 Cells J. Pharmacol. Exp. Ther., March 1, 2002; 300(3): 958 - 966. [Abstract] [Full Text] [PDF]
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 O. Hanon and D. Leys Cognitive decline and dementia in the elderly hypertensive Journal of Renin-Angiotensin-Aldosterone System, March 1, 2002; 3(1_suppl): S32 - S38. [PDF]
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Z. T. Bloomgarden Treatment Issues in Type 2 Diabetes Diabetes Care, February 1, 2002; 25(2): 390 - 394. [Full Text] [PDF]
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T. Sakurai, B. Yang, T. Takata, and K. Yokono Synaptic Adaptation to Repeated Hypoglycemia Depends on the Utilization of Monocarboxylates in Guinea Pig Hippocampal Slices Diabetes, February 1, 2002; 51(2): 430 - 438. [Abstract] [Full Text] [PDF]
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 J. A. Luchsinger, M.-X. Tang, Y. Stern, S. Shea, and R. Mayeux Diabetes Mellitus and Risk of Alzheimer's Disease and Dementia with Stroke in a Multiethnic Cohort Am. J. Epidemiol., October 1, 2001; 154(7): 635 - 641. [Abstract] [Full Text] [PDF]
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M. A. Moawad Possible Relationship Between Statin Use and Decreased Incidence of Dementia: Are We Ready for a New Indication for These Drugs? Arch Intern Med, August 13, 2001; 161(15): 1909 - 1910. [Full Text] [PDF]
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L. Gasparini, G. K. Gouras, R. Wang, R. S. Gross, M. F. Beal, P. Greengard, and H. Xu Stimulation of {beta}-Amyloid Precursor Protein Trafficking by Insulin Reduces Intraneuronal {beta}-Amyloid and Requires Mitogen-Activated Protein Kinase Signaling J. Neurosci., April 15, 2001; 21(8): 2561 - 2570. [Abstract] [Full Text] [PDF]
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A. Fontbonne, C. Berr, P. Ducimetière, and A. Alpérovitch Changes in Cognitive Abilities Over a 4-Year Period Are Unfavorably Affected in Elderly Diabetic Subjects: Results of the Epidemiology of Vascular Aging Study Diabetes Care, February 1, 2001; 24(2): 366 - 370. [Abstract] [Full Text]
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D. Knopman, L.L. Boland, T. Mosley, G. Howard, D. Liao, M. Szklo, P. McGovern, and A. R. Folsom Cardiovascular risk factors and cognitive decline in middle-aged adults Neurology, January 9, 2001; 56(1): 42 - 48. [Abstract] [Full Text] [PDF]
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J M WARDLAW Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study: the Rotterdam Scan Study J. Neurol. Neurosurg. Psychiatry, January 1, 2001; 70(1): 2 - 3. [Full Text]
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 Disease Mechanisms in Neuroscience Neuroscientist, December 1, 2000; 6(6): 419 - 421. [PDF]
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