DOI: 10.2337/diabetes.51.4.1256. Type 2 Diabetes, APOE Gene, and the Risk for Dementia and Related Pathologies

Type 2 Diabetes, APOE Gene, and the Risk for Dementia and Related Pathologies

10.2337/diabetes.51.4.1256

Crossref journal-article

American Diabetes Association

Diabetes (1167)

Abstract

Type 2 diabetes may be a risk factor for dementia, but the associated pathological mechanisms remains unclear. We evaluated the association of diabetes alone or combined with the apolipoprotein E (APOE) gene with incident dementia and neuropathological outcomes in a population-based cohort of 2,574 Japanese-American men enrolled in the Honolulu-Asia Aging Study, including 216 subjects who underwent autopsy. Type 2 diabetes was ascertained by interview and direct glucose testing. Dementia was assessed in 1991 and 1994 by clinical examination and magnetic resonance imaging and was diagnosed according to international guidelines. Logistic regression was used to assess the RR of developing dementia, and log-linear regression was used to estimate the incident rate ratio (IRR) of neuropathological outcomes. Diabetes was associated with total dementia (RR 1.5 [95% CI 1.01–2.2]), Alzheimer’s disease (AD; 1.8 [1.1–2.9]), and vascular dementia (VsD; 2.3 [1.1–5.0]). Individuals with both type 2 diabetes and the APOE ε4 allele had an RR of 5.5 (CI 2.2–13.7) for AD compared with those with neither risk factor. Participants with type 2 diabetes and the ε4 allele had a higher number of hippocampal neuritic plaques (IRR 3.0 [CI 1.2–7.3]) and neurofibrillary tangles in the cortex (IRR 3.5 [1.6–7.5]) and hippocampus (IRR 2.5 [1.5–3.7]), and they had a higher risk of cerebral amyloid angiopathy (RR 6.6, 1.5–29.6). Type 2 diabetes is a risk factor for AD and VsD. The association between diabetes and AD is particularly strong among carriers of the APOE ε4 allele. The neuropathological data are consistent with the clinical results.

Bibliography

Peila, R., Rodriguez, B. L., & Launer, L. J. (2002). Type 2 Diabetes, APOE Gene, and the Risk for Dementia and Related Pathologies. Diabetes, 51(4), 1256â1262.

Authors 3

Rita Peila (first)
Beatriz L. Rodriguez (additional)
Lenore J. Launer (additional)

References 50 Referenced 920

Dates

Type	When
Created	18 years, 5 months ago (March 6, 2007, 2:04 p.m.)
Deposited	2 years, 9 months ago (Nov. 2, 2022, 12:13 p.m.)
Indexed	56 minutes ago (Aug. 31, 2025, 6:38 a.m.)
Issued	23 years, 4 months ago (April 1, 2002)
Published	23 years, 4 months ago (April 1, 2002)
Published Print	23 years, 4 months ago (April 1, 2002)

Funders 0

None

BibTeX

@article{Peila_2002, title={Type 2 Diabetes, APOE Gene, and the Risk for Dementia and Related Pathologies}, volume={51}, ISSN={1939-327X}, url={http://dx.doi.org/10.2337/diabetes.51.4.1256}, DOI={10.2337/diabetes.51.4.1256}, number={4}, journal={Diabetes}, publisher={American Diabetes Association}, author={Peila, Rita and Rodriguez, Beatriz L. and Launer, Lenore J.}, year={2002}, month=apr, pages={1256–1262} }

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  "abstract": "<jats:p>Type 2 diabetes may be a risk factor for dementia, but the associated pathological mechanisms remains unclear. We evaluated the association of diabetes alone or combined with the apolipoprotein E (APOE) gene with incident dementia and neuropathological outcomes in a population-based cohort of 2,574 Japanese-American men enrolled in the Honolulu-Asia Aging Study, including 216 subjects who underwent autopsy. Type 2 diabetes was ascertained by interview and direct glucose testing. Dementia was assessed in 1991 and 1994 by clinical examination and magnetic resonance imaging and was diagnosed according to international guidelines. Logistic regression was used to assess the RR of developing dementia, and log-linear regression was used to estimate the incident rate ratio (IRR) of neuropathological outcomes. Diabetes was associated with total dementia (RR 1.5 [95% CI 1.01\u20132.2]), Alzheimer\u2019s disease (AD; 1.8 [1.1\u20132.9]), and vascular dementia (VsD; 2.3 [1.1\u20135.0]). Individuals with both type 2 diabetes and the APOE \u03b54 allele had an RR of 5.5 (CI 2.2\u201313.7) for AD compared with those with neither risk factor. Participants with type 2 diabetes and the \u03b54 allele had a higher number of hippocampal neuritic plaques (IRR 3.0 [CI 1.2\u20137.3]) and neurofibrillary tangles in the cortex (IRR 3.5 [1.6\u20137.5]) and hippocampus (IRR 2.5 [1.5\u20133.7]), and they had a higher risk of cerebral amyloid angiopathy (RR 6.6, 1.5\u201329.6). Type 2 diabetes is a risk factor for AD and VsD. The association between diabetes and AD is particularly strong among carriers of the APOE \u03b54 allele. The neuropathological data are consistent with the clinical results.</jats:p>",
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      "unstructured": "McCall AL: The impact of diabetes on the CNS (Review). Diabetes\u200841:557\u2013570,1992",
      "DOI": "10.2337/diabetes.41.5.557"
    },
    {
      "key": "2022031223005728000_R2",
      "doi-asserted-by": "crossref",
      "unstructured": "Kameyama M, Fushimi H, Udaka F: Diabetes mellitus and cerebral vascular disease. Diabetes Res Clin Pract\u200824 (Suppl.):S205\u2013S208,1994",
      "DOI": "10.1016/0168-8227(94)90250-X"
    },
    {
      "key": "2022031223005728000_R3",
      "doi-asserted-by": "crossref",
      "unstructured": "Mankovsky BN, Metzger BE, Molitch ME, Biller J: Cerebrovascular disorders in patients with diabetes mellitus. J Diabetes Complications\u200810:228\u2013242,1996",
      "DOI": "10.1016/S1056-8727(96)90006-9"
    },
    {
      "key": "2022031223005728000_R4",
      "doi-asserted-by": "crossref",
      "unstructured": "Munch G, Schinzel R, Loske C, Wong A, Durany N, Li JJ, Vlassara H, Smith MA, Perry G, Riederer P: Alzheimer\u2019s disease-synergistic effects of glucose deficit, oxidative stress and advanced glycation endproducts. J Neural Transm\u2008105:439\u2013461,1998",
      "DOI": "10.1007/s007020050069"
    },
    {
      "key": "2022031223005728000_R5",
      "doi-asserted-by": "crossref",
      "unstructured": "Kuusisto J, Koivisto K, Mykkanen L, Helkala E-L, Vanhanen M, Hanninen T, Kervinen K, Kesaniemi YA, Riekkinen PJ, Laakso M: Association between features of the insulin resistance syndrome and Alzheimer\u2019s disease independently of apolipoprotein e4 phenotype: cross sectional population based study. BMJ\u2008315:1045\u20131049,1997",
      "DOI": "10.1136/bmj.315.7115.1045"
    },
    {
      "key": "2022031223005728000_R6",
      "doi-asserted-by": "crossref",
      "unstructured": "Leibson CL, Rocca WA, Hanson VA, Cha R, Kokmen E, O\u2019Brien PC, Palumbo PJ: Risk of dementia among persons with diabetes mellitus: a population-based cohort study. Am J Epidemiol\u2008145:301\u2013308,1997",
      "DOI": "10.1093/oxfordjournals.aje.a009106"
    },
    {
      "key": "2022031223005728000_R7",
      "doi-asserted-by": "crossref",
      "unstructured": "Ott A, Stolk RP, van Hardkamp F, Pols HAP, Hofman A, Breteler MMB: Diabetes mellitus and the risk of dementia. Neurology\u200853:1937\u20131942,1999",
      "DOI": "10.1212/WNL.53.9.1937"
    },
    {
      "key": "2022031223005728000_R8",
      "doi-asserted-by": "crossref",
      "unstructured": "Schmechel DE, Saunders AM, Strittmatter WJ, Crain BJ, Hulette CM, Joo SH, Pericak-Vance MA, Goldgaber D, Roses AD: Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. Proc Natl Acad Sci U S A\u200890:9649\u20139653,1993",
      "DOI": "10.1073/pnas.90.20.9649"
    },
    {
      "key": "2022031223005728000_R9",
      "doi-asserted-by": "crossref",
      "unstructured": "Hebert R, Lindsay J, Verreault R, Rockwood K, Hill G, Dubois MF: Vascular dementia: incidence and risk factors in the Canadian study of health and aging. Stroke\u200831:1487\u20131493,2000",
      "DOI": "10.1161/01.STR.31.7.1487"
    },
    {
      "key": "2022031223005728000_R10",
      "doi-asserted-by": "crossref",
      "unstructured": "Dallongeville J, Lussier-Cacan S, Davignon J: Modulation of plasma triglyceride levels by apoE phenotype: a meta-analysis. J Lipid Res\u200833:447\u2013454,1992",
      "DOI": "10.1016/S0022-2275(20)41611-6"
    },
    {
      "key": "2022031223005728000_R11",
      "unstructured": "Lodder J, Boiten J: Incidence, natural history, and risk factors in lacunar infarction. Adv Neurol\u200862:213\u2013227,1993"
    },
    {
      "key": "2022031223005728000_R12",
      "doi-asserted-by": "crossref",
      "unstructured": "Stegmayr B, Asplund K: Diabetes as a risk factor for stroke: a population perspective. Diabetologia\u200838:1061\u20131068,1995",
      "DOI": "10.1007/BF00402176"
    },
    {
      "key": "2022031223005728000_R13",
      "doi-asserted-by": "crossref",
      "unstructured": "Heitner J, Dickson D: Diabetics do not have increased Alzheimer-type pathology compared with age-matched control subjects. Neurology\u200849:1306\u20131311,1997",
      "DOI": "10.1212/WNL.49.5.1306"
    },
    {
      "key": "2022031223005728000_R14",
      "doi-asserted-by": "crossref",
      "unstructured": "Kagan A, Harris BR, Winkelstein W Jr, Johnson KG, Kato H, Syme SL, Rhoads GG, Gay ML, Nichaman MZ, Hamilton HB, Tillotson J: Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California: demographic, physical, dietary and biochemical characteristics. J Chronic Dis\u200827:345\u2013364,1974",
      "DOI": "10.1016/0021-9681(74)90014-9"
    },
    {
      "key": "2022031223005728000_R15",
      "doi-asserted-by": "crossref",
      "unstructured": "White L, Petrovitch H, Ross GW, Masaki KH, Abbott RD, Teng EL, Rodriguez BL, Blanchette PL, Havlik RJ, Wergowske G, Chiu D, Foley DJ, Murdaugh C, Curb JD: Prevalence of dementia in older Japanese-American men in Hawaii: the Honolulu-Asia Aging Study. JAMA\u2008276:955\u2013960,1996",
      "DOI": "10.1001/jama.1996.03540120033030"
    },
    {
      "key": "2022031223005728000_R16",
      "doi-asserted-by": "crossref",
      "unstructured": "Teng EL, Hasegawa K, Homma A, Imai Y, Larson E, Graves A, Sugimoto K, Yamaguchi T, Sasaki H, Chiu D, et al: The Cognitive Abilities Screening Instrument (CASI): a practical test for cross-cultural epidemiological study studies of dementia. Int Psychogeriatr\u20086:45\u201358,1994",
      "DOI": "10.1017/S1041610294001602"
    },
    {
      "key": "2022031223005728000_R17",
      "unstructured": "Graves AB, Larson EB, Kukull WA, White LR, Teng EL: Screening for dementia in the community in cross-national studies: comparison between the Cognitive Avilities Screeinig Instrument and the Mini-Mental State Examination. In Alzheimer\u2019s Disease: Advances in Clinical and Basic Research. Corain B, Iqbal K, Nicolini M, Winbald B, Wisniewski H, Zatta P, Eds. New York, John Wiley & Sons,1993, p.113\u2013119"
    },
    {
      "key": "2022031223005728000_R18",
      "doi-asserted-by": "crossref",
      "unstructured": "Havlik RJ, Izmirlian G, Petrovitch H, Ross GW, Masaki K, Curb JD, Saunders AM, Foley DJ, Brock D, Launer LJ, White L: APOE-epsilon4 predicts incident AD in Japanese-American men: the Honolulu-Asia Aging study. Neurology\u200854:1526\u20131529,2000",
      "DOI": "10.1212/WNL.54.7.1526"
    },
    {
      "key": "2022031223005728000_R19",
      "unstructured": "American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders. 3rd ed., revised. Washington, DC, America Psychiatric Association,1987"
    },
    {
      "key": "2022031223005728000_R20",
      "doi-asserted-by": "crossref",
      "unstructured": "McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer\u2019s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services task force on Alzheimer\u2019s disease. Neurology\u200834:939\u2013944,1984",
      "DOI": "10.1212/WNL.34.7.939"
    },
    {
      "key": "2022031223005728000_R21",
      "doi-asserted-by": "crossref",
      "unstructured": "Chiu HC, Victoroff JI, Margolin D, Jagust W, Shankle R, Katzman R: Criteria for the diagnosis of ischemic vascular dementia proposed by the state of California Alzheimer\u2019s Disease Diagnostic and Treatment Centers. Neurology\u200842:473\u2013480,1992",
      "DOI": "10.1212/WNL.42.3.473"
    },
    {
      "key": "2022031223005728000_R22",
      "unstructured": "American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: America Psychiatric Association,1994"
    },
    {
      "key": "2022031223005728000_R23",
      "doi-asserted-by": "crossref",
      "unstructured": "McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA, Salmon DP, Lowe J, Mirra SS, Byrne EJ, Lennox G, Quinn NP, Edwardson JA, Ince PG, Bergeron C, Burns A, Miller BL, Lovestone S, Collerton D, Jansen EN, Ballard C, de Vos RA, Wilcock GK, Jellinger KA, Perry RH: Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology\u200847:1113\u20131124,1996",
      "DOI": "10.1212/WNL.47.5.1113"
    },
    {
      "key": "2022031223005728000_R24",
      "doi-asserted-by": "crossref",
      "unstructured": "Petrovitch H, White LR, Ross GW, Steinhorn SC, Li CY, Masaki KH, Davis DG, Nelson J, Hardman J, Curb JD, Blanchette PL, Launer LJ, Yano K, Markesbery WR: Accuracy of Clinical Criteria for AD in the Honolulu-Asia Aging Study, a population based study. Neurology\u200857:226\u2013234,2001",
      "DOI": "10.1212/WNL.57.2.226"
    },
    {
      "key": "2022031223005728000_R25",
      "doi-asserted-by": "crossref",
      "unstructured": "Gearing M, Mirra SS, Hedreen JC, Sumi SM, Hansen LA, Heyman A: The Consortium to Establish a Registry for Alzheimer\u2019s Disease (CERAD). Part X. Neuropathology confirmation of the clinical diagnosis of Alzheimer\u2019s disease. Neurology\u200845:461\u2013466,1995",
      "DOI": "10.1212/WNL.45.3.461"
    },
    {
      "key": "2022031223005728000_R26",
      "doi-asserted-by": "crossref",
      "unstructured": "Petrovitch H, White LR, Izmirilian G, Ross GW, Havlik RJ, Markesbery W, Nelson J, Davis DG, Hardman J, Foley DJ, Launer LJ: Midlife blood pressure and neuritic plaques, neurofibrillary tangles, and brain weight at death: the HAAS. Neurobiol Aging\u200821:57\u201362,2000",
      "DOI": "10.1016/S0197-4580(00)00106-8"
    },
    {
      "key": "2022031223005728000_R27",
      "unstructured": "Pfeifer LA, White LR, Nelson JS, Ross GW, Petrovitch H, Launer LJ: Association between cerebral amyloid angiopathy and dementia: the Honolulu-Asia Aging study (Abstract). Neurology\u2008(Suppl. 3):A323,2000"
    },
    {
      "key": "2022031223005728000_R28",
      "doi-asserted-by": "crossref",
      "unstructured": "Vinters HV, Gilbert JJ: Cerebral amyloid angiopathy: incidence and complications in the aging brain. II. The distribution of vascular amyloid changes. Stroke\u200814:924\u2013928,1983",
      "DOI": "10.1161/01.STR.14.6.924"
    },
    {
      "key": "2022031223005728000_R29",
      "doi-asserted-by": "crossref",
      "unstructured": "The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care\u200820:1183\u20131197,1997",
      "DOI": "10.2337/diacare.20.7.1183"
    },
    {
      "key": "2022031223005728000_R30",
      "doi-asserted-by": "crossref",
      "unstructured": "Wahl PW, Savage PJ, Psaty BM, Orchard TJ, Robbins JA, Tracy RP: Diabetes in older adults: comparison of 1997 American diabetes association classification of diabetes mellitus with 1985 WHO classification. Lancet\u2008352:1012\u20131015,1998",
      "DOI": "10.1016/S0140-6736(98)04055-0"
    },
    {
      "key": "2022031223005728000_R31",
      "doi-asserted-by": "crossref",
      "unstructured": "Meneilly GS, Hill A: Alterations in glucose metabolism in patients with Alzheimer\u2019s disease. J Am Geriatr Soc\u200841:710\u2013714,1993",
      "DOI": "10.1111/j.1532-5415.1993.tb07458.x"
    },
    {
      "key": "2022031223005728000_R32",
      "doi-asserted-by": "crossref",
      "unstructured": "Hixson JE, Vernier DT: Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res\u200831:545\u2013548,1990",
      "DOI": "10.1016/S0022-2275(20)43176-1"
    },
    {
      "key": "2022031223005728000_R33",
      "doi-asserted-by": "crossref",
      "unstructured": "Locke PA, Conneally PM, Tanzi RE, Gusella JF, Haines JL: Apolipoprotein E4 allele and Alzheimer disease: examination of allelic association and effect on age at onset in both early- and late-onset cases. Genet Epidemiol\u200812:83\u201392,1995",
      "DOI": "10.1002/gepi.1370120108"
    },
    {
      "key": "2022031223005728000_R34",
      "doi-asserted-by": "crossref",
      "unstructured": "Syme SL, Marmot MG, Kagan A, Kato H, Rhoads G: Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and California: introduction. Am J Epidemiol\u2008102:477\u2013480,1975",
      "DOI": "10.1093/oxfordjournals.aje.a112185"
    },
    {
      "key": "2022031223005728000_R35",
      "doi-asserted-by": "crossref",
      "unstructured": "Newman AB, Sutton-Tyrrell K, Vogt MT, Kuller LH: Morbidity and mortality in hypertensive adults with a low ankle/arm blood pressure index. JAMA\u2008270:487\u2013489,1993",
      "DOI": "10.1001/jama.270.4.487"
    },
    {
      "key": "2022031223005728000_R36",
      "doi-asserted-by": "crossref",
      "unstructured": "Ottman R: Gene-environment interaction: definitions and study designs. Prev Med\u200825:764\u2013770,1996",
      "DOI": "10.1006/pmed.1996.0117"
    },
    {
      "key": "2022031223005728000_R37",
      "doi-asserted-by": "crossref",
      "unstructured": "Frome EL, Checkoway H: Epidemiologic programs for computers and calculators: use of Poisson regression models in estimating incidence rates and ratios. Am J Epidemiol\u2008121:309\u2013323,1985",
      "DOI": "10.1093/oxfordjournals.aje.a114001"
    },
    {
      "key": "2022031223005728000_R38",
      "doi-asserted-by": "crossref",
      "unstructured": "Curb JD, Rodriguez BL, Abbott RD, Petrovitch H, Ross GW, Masaki KH, Foley D, Blanchette PL, Harris T, Chen R, White LR: Longitudinal association of vascular and Alzheimer\u2019s dementias, diabetes, and glucose tolerance. Neurology\u200852:971\u2013975,1999",
      "DOI": "10.1212/WNL.52.5.971"
    },
    {
      "key": "2022031223005728000_R39",
      "doi-asserted-by": "crossref",
      "unstructured": "Harris MI, Flegal KM, Cowie CC, Eberhardt MS, Goldstein DE, Little RR, Wiedmeyer HM, Byrd-Holt DD: Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults: the Third National Health and Nutrition Examination Survey, 1988\u20131994. Diabetes Care\u200821:518\u2013524,1998",
      "DOI": "10.2337/diacare.21.4.518"
    },
    {
      "key": "2022031223005728000_R40",
      "doi-asserted-by": "crossref",
      "unstructured": "Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS): Pathological correlates to late-onset dementia in a multicenter, community-based population in England and Wales. Lancet\u2008357:169\u2013175,2001",
      "DOI": "10.1016/S0140-6736(00)03589-3"
    },
    {
      "key": "2022031223005728000_R41",
      "doi-asserted-by": "crossref",
      "unstructured": "Erkinjuntti T: Cerebrovascular dementia: pathophysiology, diagnosis and treatment. CNS Drugs\u200812:35\u201346,1999",
      "DOI": "10.2165/00023210-199912010-00004"
    },
    {
      "key": "2022031223005728000_R42",
      "doi-asserted-by": "crossref",
      "unstructured": "Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR: Brain infarction and the clinical expression of Alzheimer disease: the Nun Study. JAMA\u2008277:813\u2013817,1997",
      "DOI": "10.1001/jama.277.10.813"
    },
    {
      "key": "2022031223005728000_R43",
      "doi-asserted-by": "crossref",
      "unstructured": "Selkoe DJ, Ihara Y, Salazar FJ: Alzheimer\u2019s disease: insolubility of partially purified paired helical filaments in sodium dodecyl sulfate and urea. Science\u2008215:1243\u20131245,1982",
      "DOI": "10.1126/science.6120571"
    },
    {
      "key": "2022031223005728000_R44",
      "doi-asserted-by": "crossref",
      "unstructured": "Smith MA, Taneda S, Richey PL, Miyata S, Yan SD, Stern D, Stern D, Sayre LM, Monnier VM, Perry G: Advanced Maillard reaction end products are associated with Alzheimer disease pathology. Proc Natl Acad Sci U S A\u200891:5710\u20135714,1994",
      "DOI": "10.1073/pnas.91.12.5710"
    },
    {
      "key": "2022031223005728000_R45",
      "doi-asserted-by": "crossref",
      "unstructured": "Munch G, Mayer S, Michaelis J, Hipkiss AR, Riederer P, Muller R, Neumann A, Schinzel R, Cunningham AM: Influence of advanced glycation end-products and AGE-inhibitors on nucleation-dependent polymerization of beta-amyloid peptide. Biochim Biophys Acta\u20081360:17\u201329,1997",
      "DOI": "10.1016/S0925-4439(96)00062-2"
    },
    {
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