Abstract
Higher circulating concentrations of cellular adhesion molecules (CAMs) can be used as markers of endothelial dysfunction. Given that the brain is highly vascularized, we assessed whether endothelial function is associated with cognitive performance. Within the Coronary Artery Risk Development in Young Adults (CARDIA) Study, excluding N = 54 with stroke before year 25, we studied CAMs among N = 2,690 black and white men and women in CARDIA year 7 (1992-1993, ages 25-37) and N = 2,848 in CARDIA year 15 (2000-2001, ages 33-45). We included subjects with levels of circulating soluble CAMs measured in year 7 or 15 and cognitive function testing in year 25 (2010-2011, ages 43-55). Using multiple regression analysis, we evaluated the association between CAMs and year 25 cognitive test scores: Rey Auditory Verbal Learning Test (RAVLT, memory), Digit Symbol Substitution Test (DSST, speed of processing), and the Stroop Test (executive function). All CAM concentrations were greater in year 15 vs. year 7. Adjusting for age, race, sex, education, smoking, alcohol, diet, physical activity, participants in the fourth vs. the first quartile of CARDIA year 7 of circulating intercellular adhesion molecule-1 (ICAM-1) scored worse on RAVLT, DSST, and Stroop Test (p ≤ 0.05) in CARDIA year 25. Other CAMs showed little association with cognitive test scores. Findings were similar for ICAM-1 assessed at year 15. Adjustment for possibly mediating physical factors attenuated the findings. Higher circulating ICAM-1 at average ages 32 and 40 was associated with lower cognitive skills at average age 50. The study is consistent with the hypothesis that endothelial dysfunction is associated with worse short-term memory, speed of processing, and executive function.
Highlights
Decline in cognitive function is a concern among older adults as it rises with age [1, 2] and leads to loss of independent function [3]
The years of educational attainment, amount of physical activity, Body mass index (BMI), and concentrations of LDL cholesterol, triglycerides, and intercellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), P-selectin, E-selectin, and fractalkine all increased in year 15 compared to year 7
In year 7, less educational attainment, less physical activity, and lower quality diet were associated with higher ICAM-1, P-selectin, and E-selectin concentrations, while current smoking, higher BMI, hypertension, adverse blood lipid profile, and higher C-reactive protein were associated with higher concentrations of
Summary
Decline in cognitive function is a concern among older adults as it rises with age [1, 2] and leads to loss of independent function [3]. Because the brain is highly vascularized, impaired endothelial function may play a role in progression to dementia. Endothelial damage is considered to be expressed by elevated levels of cellular adhesion molecules (CAMs) situated on vascular endothelial cells. The chemokine fractalkine expresses on endothe lial cells and plays an important role in leukocyte adhesion and migration [6]. The capacity to maintain homeostasis reduces, predisposing to vascular disease and brain hypoperfusion [7,8,9]. Even less attention has been given to the relationship between endothelial dysfunction and lower cognitive function among healthy adults. It would be ideal to collect measurements of endothelial dysfunction biomarkers before symptoms of neurodegenerative diseases occur in a population-based study or signs and symptoms of cognitive dysfunction occur among healthy adults
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