Cholesterol, transferrin saturation, and the development of dementia and Alzheimer's disease: results from an 18-year population-based cohort.

BACKGROUND AND OBJECTIVES Oxidative stress plays a role in Alzheimer's disease (AD), and iron and cholesterol together have been linked to oxidative stress. This study examined the relationship between transferrin saturation (TS) and cholesterol to see if both are necessary to increase the risk for the subsequent development of AD. METHODS We analyzed data from US adults (ages 40-74 years at baseline) followed from baseline in 1971-1974 to 1992 (n=6,558) in the cohort study, the National Health and Nutrition Examination Survey I Epidemiologic Followup Study (NHEFS). RESULTS The unadjusted relative risk of developing AD when both TS and cholesterol were at the 75th percentile was 3.19 (95% CI, 1.31-7.75). In adjusted models when only one marker was elevated, there was no significant increased risk for AD. The risk of AD increased as both markers increased. Even at the 85th percentile, individuals had no significant risk of AD when only having elevated cholesterol (>280 mg/dl) but not elevated TS (39.6%). Findings were similar for individuals with elevated TS but not elevated cholesterol. CONCLUSIONS In this population-based cohort, the risk of developing AD when one has both elevated cholesterol and elevated TS is much larger than the risk associated with elevation of either of these factors alone.

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