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.
Article: Is obesity a brain disease?[Show abstract] [Hide abstract]
ABSTRACT: That the brain is involved in the pathogenesis and perpetuation of obesity is broadly self-intuitive, but traditional evaluation of this relationship has focused on psychological and environment-dependent issues, often referred to as the "it's all in the head" axiom. Here we review evidence that excessive nutrition or caloric flux, regardless of its primary trigger, elicits a biological trap which imprints aberrant energy control circuits that tend to worsen with the accumulation of body fat. Structural and functional changes in the brain can be recognized, such as hypothalamic inflammation and gliosis, reduction in brain volume, reduced regional blood flow or diminished hippocampal size. Such induced changes collectively translate into a vicious cycle of deranged metabolic control and cognitive deficits, some of which can be traced back even to childhood or adolescence. Much like other components of the obese state, brain disease is inseparable from obesity itself and requires better recognition to allow future therapeutic targeting.Neuroscience & Biobehavioral Reviews 08/2013; · 10.28 Impact Factor
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