Abstract 44: Soluble CD14 and Risk of Incident Cognitive Impairment: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Abstract

Introduction: Black adults in the U.S. experience a greater burden of systemic inflammation and cognitive impairment and dementia compared with White adults. Increasing evidence suggests peripheral inflammation is a risk factor for cognitive decline, however few longitudinal studies have investigated these relationships. CD14 is a pattern recognition receptor expressed by monocytes and macrophages that promotes inflammation. Concentrations of the soluble form of CD14 (sCD14) vary by race, and higher sCD14 was associated with incident coronary heart disease (CHD) and stroke in Black but not White participants in the REGARDS cohort study. We hypothesized higher sCD14 would also be more strongly associated with incident cognitive impairment (ICI) in Black compared to White adults. Methods: We performed a nested case-control study of ICI in the REGARDS study, a biracial cohort of 30,239 American adults ≥45 years old. Cases were 495 participants without cognitive impairment or stroke at baseline who developed ICI during a median 3.5 years of follow-up based on abnormal scores on ≥2 of 3 cognitive tests. 587 controls were selected from a cohort random sample and free of cognitive impairment or stroke at baseline. Logistic regression models estimated odds ratios (OR) of ICI by concentration of sCD14 measured from stored baseline serum samples. We tested for a sCD14-by-race interaction a priori. Results: The sCD14-by-race interaction term was statistically significant in each model (p-interaction <0.05). In analyses stratified by race, adjusting for demographic factors (age, sex, and region), a 1-SD increment sCD14 was associated with a 40% higher odds of ICI among Black adults (OR: 1.40; 95% CI: 1.07, 1.95) with no association among White adults (OR: 1.08; 95% CI: 0.90, 1.28). In models adjusted for cognitive and vascular risk factors (income, education, systolic blood pressure, hypertension medication use, dyslipidemia, BMI, history of heart disease, atrial fibrillation, diabetes, smoking, and alcohol use), the relationship was attenuated in Black participants (OR: 1.33; 95% CI: 0.96, 1.84) and remained null among White participants (OR: 0.99; 95% CI: 0.81, 1.22). Comparing those with sCD14 concentration >90th percentile to below, adjusted for risk factors, Black participants had a 2.47 (95% CI: 1.08, 5.67) higher odds of ICI with no association in White participants (OR: 0.91; 95% CI: 0.46, 1.80). Discussion: Higher sCD14 was associated with ICI risk in Black but not White adults, similar to prior observations for stroke. Results suggest that sCD14-associated inflammatory responses may be a risk factor for ICI among Black adults.