Risk factors for dementia development are not well-defined. We evaluated several factors alone and in combination in a unique cohort of Caucasian volunteers over an approximately 6-year observation window using a nested case/control design. Factors included: apolipoprotein E (ApoE) gene variants (the E4 allele is the strongest confirmed genetic predisposing factor for Alzheimer's disease), the hemochromatosis-HFE gene mutations (H63D and C282Y), diabetes, and stroke. At study entry, subjects were ≥65 years of age (M ± SD = 73.0 ± 4.9), had an MMSE score ≥24, and no evidence of cerebrovascular disease or current depression. Genotyping was completed on 163 available DNA samples from three different groups at the study end: those who still had normal cognitive function; those who had developed dementia; and those with Mild Cognitive Impairment (MCI). Analyses were interpreted at the 95% confidence level without Bonferroni corrections. In the subgroup with dementia, all cases of diabetes were type 2 and present at study entry, whereas all strokes occurred during the study. The results highlight apparently synergistic interactions between genetic and medical risk factors for dementia development, gender differences in risk factors, and involvement of HFE mutations. Having E4 (i.e., either of E3/4 or E4/4), C282Y, H63D, diabetes, or stroke alone did not attain significance. Significant predisposing factors with post-hoc power ≥80% were: E4 homozygosity (E4/4)males+females, odds ratio (OR) = 56.0); E4+diabetes (males+females, OR = 13.7; E4+H63D+diabetes (females, OR = 52.0); E4+stroke (males, OR = 46.5). The importance of preventing diabetes and stroke to ward off dementia and the possible role of iron dysmetabolism in dementia are discussed.
Background/Synopsis: While the role of low density lipoprotein cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] in predicting coronary heart disease (CHD) and cardiovascular disease (CVD) events is well-established, it is unclear whether Lp(a) remains associated across all levels of LDL-C.Objective/Purpose: We examined in older higher risk adults the relation of these two measures to CHD and CVD events.Methods: The Cardiovascular Health Study is a prospective population-based cohort study of CVD in men and women aged 65 or older (mean age 73.8, 42.4% female). We included 3251 high CVD risk subjects (prior CVD, diabetes or 10-year estimated Framingham CVD risk .20%) with LDL-C, lp(a) and other risk factor measures studied from baseline examinations in 1990-1992 with follow-up through 2011. Cox regression adjusted for risk factors examined the combined relation of LDL-C and Lp(a) categories in relation to future hard CHD (myocardial infarction and CHD death) and CVD events (hard CHD, ischemic stroke, or CVD death).
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