P2‐415: Association of Baseline Lipids with 20‐year Cognitive Change: the ARIC Neurocognitive Study

Midlife total cholesterol appears to be associated with an increased risk of dementia and cognitive impairment. However, few studies have considered associations between measures of blood lipids, including lipid fractions, and within-person cognitive change over a substantial follow-up period. Using data from up to 13,997 eligible participants of the Atherosclerosis Risk in Communities study, we estimated the association between total cholesterol, low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c), and triglycerides at Visit 2 (baseline, 1990-1992) with rate of cognitive decline across ARIC Visits 2, 4 (1996-1998), and 5 (2011-2013) using linear mixed effects models. Specifically, we considered decline in performance on three tests, the Digit-Symbol Substitution Test (DSST; executive function), a Delayed Word Recall Test (DWRT; memory), and a Word Fluency Test (WFT; verbal fluency), as well as a summary measure (“overall cognition”) based on the average of standardized scores across these three tests. On average, study participants were 58 years old (range: 46 to 70 years) at baseline. Elevated total cholesterol, LDL-c, and triglycerides were associated with greater 20-year decline in DSST scores. Using ATP-III guideline categories, those with high versus desirable total cholesterol (>240 versus <200 mg/dL) had 0.05 SD greater 20-year decline in DSST scores (95%CI: -0.08, -0.01). Similarly, 20-year decline in DSST scores was 0.06 SD units (95%CI: -0.10, -0.01) greater in those with high (160-189 mg/dL) versus optimal (<100 mg/dL) LDL-c, and 20-year decline in DSST scores was 0.08 SD units (95%CI: -0.12, -0.04) greater in those with high (200-499 mg/dL) versus normal (<150 mg/dL) triglycerides. Higher total cholesterol and triglycerides were also associated with greater 20-year decline in overall cognition. We did not observe any associations between HDL-c and cognitive change. Results were materially unchanged in sensitivity analyses designed to address informative missingness. Elevated total cholesterol, LDL-c and triglycerides at baseline were associated with faster decline in executive function over the subsequent decades. The magnitude of these associations is roughly 60% to 100% of that previously observed with hypertension in this sample, suggesting that prior lipid levels are a notable risk factor for decline in executive function.