Abstract
Introduction: Cardiovascular risk factors are reportedly predictive of cognitive decline and dementia but the association between the extent and severity of subclinical atherosclerosis with cognitive decline remains understudied. Hypothesis: The systemic burden of atherosclerosis measured non-invasively is associated with the rate of decline in domain-specific (memory, executive function and language) and global cognition from mid-life to late life. Methods: Members of the ARIC cohort (N=12313; 58% women, 24% African American (AA), 76% white) aged 46-70 years at their 1990-1992 examination were followed through 2011-2013. Participants with prevalent stroke, myocardial infarction or coronary heart disease were excluded. Atherosclerosis at baseline (n=5217) was assessed by carotid artery b-mode ultrasound (presence and number of plaques, bilaterally) and by ankle-brachial index <0.9 measured with an oscillometric device. Tests of memory (Delayed Word Recall Test), executive function (Digit Symbol Substitution Test), and language (Word Fluency Test) were administered in 1990-92, 1996-98 and 2011-13. Test-specific z scores were calculated at each exam based on the means and standard deviations at baseline. A global cognition z score was estimated by averaging the 3 test-specific z scores and standardizing to baseline. Race-stratified linear random effects regression was used to estimate the association between subclinical atherosclerosis and 20-year declines in domain-specific cognition and global cognition. We adjusted for age, sex and level of education. Inverse probability weighting (IPW) was used to limit bias due to attrition. Results: In AA, the presence of carotid plaque and/or ABI <0.90 (n=490) was associated with a lower memory z score (Beta=-0.10, 95% confidence interval, CI: -0.18, -0.02), a lower language z score (Beta=-0.07, 95% CI: -0.14,-0.002) and a lower global cognition z score at baseline (Beta=-0.09, 95% CI: -0.16, -0.02), but not with rates of change in any cognitive score. Among whites at baseline, individuals with subclinical atherosclerosis (n=4099) exhibited lower executive function (Beta=-0.05, 95% CI: -0.08, -0.02) and global cognition (Beta=-0.04, 95% CI: -0.07, -0.01). White participants with subclinical atherosclerosis had a greater 20-year rate of decline in global cognition (Beta=-0.06, 95% CI: -0.10, -0.00) compared to those without subclinical atherosclerosis. Conclusions: Baseline memory, language, and global cognition in AA and executive function and global cognition in whites were lower among those with non-invasively ascertained atherosclerosis compared to those without, independent of covariates in the model. Among whites, subclinical clinical measures of atherosclerosis in mid-life may be indicative of modest, but measurable declines in cognition after additional adjustment for potential bias due to attrition.
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