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Meta-analysis of Alzheimer's disease risk with obesity, diabetes, and related disorders.

Abstract

BACKGROUND

Late-onset Alzheimer's disease (AD) is a multifactorial and heterogeneous disorder with major risk factors including advanced age, presence of an apolipoprotein E epsilon4 (APOE4) allele, and family history of AD. Other risk factors may be obesity and diabetes and related disorders, which are highly prevalent.

METHODS

We reviewed longitudinal epidemiological studies of body mass, diabetes, metabolic syndrome, and glucose and insulin levels on risk for AD. We conducted meta-analyses of the results from these studies.

RESULTS

For obesity assessed by body mass index, the pooled effect size for AD was 1.59 (95% confidence interval [CI] 1.02-2.5; z = 2.0; p = .042), and for diabetes, the pooled effect size for AD was 1.54 (95% CI 1.33-1.79; z = 5.7; p < .001). Egger's test did not find significant evidence for publication bias in the meta-analysis for obesity (t = -1.4, p = .21) or for diabetes (t = -.86, p = .42). Since these disorders are highly comorbid, we conducted a meta-analysis combining all studies of obesity, diabetes, and abnormal glucose or insulin levels, which yielded a highly significant pooled effect size for AD of 1.63 (95% CI 1.39-1.92; z = 5.9; p < .001).

CONCLUSIONS

Obesity and diabetes significantly and independently increase risk for AD. Though the level of risk is less than that with the APOE4 allele, the high prevalence of these disorders may result in substantial increases in future incidence of AD. Physiological changes common to obesity and diabetes plausibly promote AD.

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  • Publisher Full Text
  • Authors

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    Source

    Biological psychiatry 67:6 2010 Mar 15 pg 505-12

    MeSH

    Aged
    Alzheimer Disease
    Apolipoprotein E4
    Body Mass Index
    Diabetes Complications
    Female
    Glucose
    Humans
    Insulin
    Longitudinal Studies
    Male
    Mental Status Schedule
    Middle Aged
    Obesity
    Overweight
    Proportional Hazards Models
    PubMed
    Retrospective Studies
    Risk Factors

    Pub Type(s)

    Journal Article
    Meta-Analysis

    Language

    eng

    PubMed ID

    19358976

    Citation

    TY - JOUR T1 - Meta-analysis of Alzheimer's disease risk with obesity, diabetes, and related disorders. AU - Profenno,Louis A, AU - Porsteinsson,Anton P, AU - Faraone,Stephen V, Y1 - 2009/04/09/ PY - 2008/9/16/received PY - 2009/2/10/revised PY - 2009/2/19/accepted PY - 2009/4/9/aheadofprint PY - 2009/4/11/entrez PY - 2009/4/11/pubmed PY - 2010/5/19/medline SP - 505 EP - 12 JF - Biological psychiatry JO - Biol. Psychiatry VL - 67 IS - 6 N2 - BACKGROUND: Late-onset Alzheimer's disease (AD) is a multifactorial and heterogeneous disorder with major risk factors including advanced age, presence of an apolipoprotein E epsilon4 (APOE4) allele, and family history of AD. Other risk factors may be obesity and diabetes and related disorders, which are highly prevalent. METHODS: We reviewed longitudinal epidemiological studies of body mass, diabetes, metabolic syndrome, and glucose and insulin levels on risk for AD. We conducted meta-analyses of the results from these studies. RESULTS: For obesity assessed by body mass index, the pooled effect size for AD was 1.59 (95% confidence interval [CI] 1.02-2.5; z = 2.0; p = .042), and for diabetes, the pooled effect size for AD was 1.54 (95% CI 1.33-1.79; z = 5.7; p < .001). Egger's test did not find significant evidence for publication bias in the meta-analysis for obesity (t = -1.4, p = .21) or for diabetes (t = -.86, p = .42). Since these disorders are highly comorbid, we conducted a meta-analysis combining all studies of obesity, diabetes, and abnormal glucose or insulin levels, which yielded a highly significant pooled effect size for AD of 1.63 (95% CI 1.39-1.92; z = 5.9; p < .001). CONCLUSIONS: Obesity and diabetes significantly and independently increase risk for AD. Though the level of risk is less than that with the APOE4 allele, the high prevalence of these disorders may result in substantial increases in future incidence of AD. Physiological changes common to obesity and diabetes plausibly promote AD. SN - 1873-2402 UR - https://www.unboundmedicine.com/medline/citation/19358976/full_citation L2 - http://linkinghub.elsevier.com/retrieve/pii/S0006-3223(09)00226-1 ER -