Abstract

Background: Exposure to elevated plasma non-high density lipoprotein cholesterol (non-HDL-C) levels during adulthood has been associated with higher risk of cardiovascular events. However, whether long term non-HDL-C variability from childhood impacts midlife cognitive function (CF) is unclear. Hypothesis: We hypothesized that higher long-term non-HDL-C variability from childhood would be associated with worse midlife CF measures. Aim: We aimed to identify the effect of long term lipid variability from childhood on midlife CF. Methods: We studied 1,249 midlife participants of the Bogalusa Heart Study (age at baseline: mean 9.5 years+/- standard deviation(SD)3.5 years; age at midlife: mean 48.2 years+/- SD 5.2 years; 59.8 % women(747 of 1249), 34.3% Black(428 of 1249)) with ≥3 lipid measurements across follow up. Non-HDL-C levels were obtained as total cholesterol - HDL cholesterol. Visit-to visit non-HDL-C variability from childhood was estimated by the deviation from age predicted values (DEV), and residual SD (RSD). Non-HDL-C measurements were fitted in random-effects models stratified by race and sex, to produce individual growth curves. DEV and RSD were measured as the mean and SD of the residuals of observed and predicted non-HDL levels. Midlife CF was measured by 10 neuropsychological (NP) tests. NP test results were categorized into 3 distinct NP profiles (optimal, average, and mixed-low) using cluster analysis. Associations between non-HDL-C and NP profiles were analyzed using multinomial logistic regression models, adjusting for education status and the mean of non-HDL-C measurements from childhood to midlife. DEV and RSD were standardized to z-scores before conducting regression analysis. Interactions according to race and sex were performed. Results: The odds of having a mixed-low CF compared to optimal increased by 31.1% (95% CI 1.075, 1.599) for every 1 SD increase in DEV, and by 30.5% (95% CI 1.069, 1.591) for every 1 SD increase in RSD, respectively, adjusted for education status and mean non-HDL-C levels. Neither race or sex were found to modify the associations of DEV nor RSD on CF. Conclusions: Higher long-term non-HDL-C variability was linked to poorer midlife CF. Further studies are needed to identify the impact of long-term non-HDL-C variability in the association of cardiometabolic risk factors and midlife CF.

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