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Diabetes and overweight associate with non-APOE4 genotype in an Alzheimer's disease population.

Abstract

Type 2 diabetes is a risk factor for late-onset Alzheimer's disease (AD), and studies suggest that pathogenic effects of diabetes and insulin resistance may be associated with non-APOE4 AD. Therefore, we examined association of the APOE4 allele with diabetes in an AD population. Retrospective and cross-sectional clinical and APOE-genotype data on 465 cases with probable or definite AD previously ascertained by the National Institute of Mental Health Genetics Initiative were analyzed by regression analysis. Dependent variables included presence of APOE4 alleles and AD onset age. Diabetes was the independent variable and covariates included gender, hypertension, and other potentially confounding variables. We also examined for interactions involving weight status as overweight and obesity are independent risk factors for insulin resistance, diabetes and AD. Prevalence of diabetes was 13% among AD cases without an APOE4 allele and 5-6% among AD cases with one or two APOE4 alleles. Odds ratio for diabetes was 0.26 [95% CI: 0.09-0.73; P = 0.011] by APOE4 status after adjusting for all covariates. Diabetes did not associate with AD onset age. Among other independent variables included in the model, APOE4 and diuretic medication treatment were associated with AD onset age. In a subset of cases with body mass index determinations, overweight also exhibited an inverse association with APOE4 and associated with decreased non-APOE4 AD onset age. Pathogenic mechanisms associated with diabetes and overweight are enriched in AD cases without an APOE4 allele.

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  • Authors+Show Affiliations

    ,

    Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse VA Medical Center, Syracuse, New York 13210, USA. profennl@upstate.edu

    Source

    MeSH

    Age of Onset
    Aged
    Aged, 80 and over
    Alzheimer Disease
    Apolipoprotein E4
    Cohort Studies
    Diabetes Mellitus, Type 2
    Female
    Genetic Linkage
    Genetics, Population
    Genotype
    Humans
    Male
    Middle Aged
    Overweight
    Prevalence

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, Non-P.H.S.

    Language

    eng

    PubMed ID

    18189240

    Citation

    Profenno, Louis A., and Stephen V. Faraone. "Diabetes and Overweight Associate With non-APOE4 Genotype in an Alzheimer's Disease Population." American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics, vol. 147B, no. 6, 2008, pp. 822-9.
    Profenno LA, Faraone SV. Diabetes and overweight associate with non-APOE4 genotype in an Alzheimer's disease population. Am J Med Genet B Neuropsychiatr Genet. 2008;147B(6):822-9.
    Profenno, L. A., & Faraone, S. V. (2008). Diabetes and overweight associate with non-APOE4 genotype in an Alzheimer's disease population. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics, 147B(6), pp. 822-9. doi:10.1002/ajmg.b.30694.
    Profenno LA, Faraone SV. Diabetes and Overweight Associate With non-APOE4 Genotype in an Alzheimer's Disease Population. Am J Med Genet B Neuropsychiatr Genet. 2008 Sep 5;147B(6):822-9. PubMed PMID: 18189240.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Diabetes and overweight associate with non-APOE4 genotype in an Alzheimer's disease population. AU - Profenno,Louis A, AU - Faraone,Stephen V, PY - 2008/1/15/pubmed PY - 2008/12/17/medline PY - 2008/1/15/entrez SP - 822 EP - 9 JF - American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics JO - Am. J. Med. Genet. B Neuropsychiatr. Genet. VL - 147B IS - 6 N2 - Type 2 diabetes is a risk factor for late-onset Alzheimer's disease (AD), and studies suggest that pathogenic effects of diabetes and insulin resistance may be associated with non-APOE4 AD. Therefore, we examined association of the APOE4 allele with diabetes in an AD population. Retrospective and cross-sectional clinical and APOE-genotype data on 465 cases with probable or definite AD previously ascertained by the National Institute of Mental Health Genetics Initiative were analyzed by regression analysis. Dependent variables included presence of APOE4 alleles and AD onset age. Diabetes was the independent variable and covariates included gender, hypertension, and other potentially confounding variables. We also examined for interactions involving weight status as overweight and obesity are independent risk factors for insulin resistance, diabetes and AD. Prevalence of diabetes was 13% among AD cases without an APOE4 allele and 5-6% among AD cases with one or two APOE4 alleles. Odds ratio for diabetes was 0.26 [95% CI: 0.09-0.73; P = 0.011] by APOE4 status after adjusting for all covariates. Diabetes did not associate with AD onset age. Among other independent variables included in the model, APOE4 and diuretic medication treatment were associated with AD onset age. In a subset of cases with body mass index determinations, overweight also exhibited an inverse association with APOE4 and associated with decreased non-APOE4 AD onset age. Pathogenic mechanisms associated with diabetes and overweight are enriched in AD cases without an APOE4 allele. SN - 1552-485X UR - https://www.unboundmedicine.com/medline/citation/18189240/Diabetes_and_overweight_associate_with_non_APOE4_genotype_in_an_Alzheimer's_disease_population_ L2 - https://doi.org/10.1002/ajmg.b.30694 DB - PRIME DP - Unbound Medicine ER -