Coronary Artery Calcium Progression and Cognitive Function in Midlife-The CARDIA Study (Coronary Artery Risk Development in Young Adults)

Circ Popul Health Outcomes. 2026 Feb 16:e012646. doi: 10.1161/CIRCOUTCOMES.125.012646. Online ahead of print.

ABSTRACT

BACKGROUND: We aimed to examine how coronary artery calcium (CAC) and its progression relate to cognitive function in midlife, an important time for cognitive aging.

METHODS: We studied participants enrolled in the prospective CARDIA study (Coronary Artery Risk Development in Young Adults), a longitudinal cohort of Black and White adults aged 18 to 30 years at baseline, who completed CAC measurements using computed tomography at year 15 (2000-2001; our baseline), had at least 1 follow-up CAC measurement at years 20 (2005-2006) or 25 (2010-2011), and completed cognitive assessments with a battery of 5 tests at years 30 (2015-2016) or 35 (2020-2022). CAC progression was defined as: (1) CAC >0 at follow-up among participants with baseline CAC=0; (2) an annualized change of ≥10 units at follow-up among those with 0<baseline CAC <100; or (3) an annualized percent change ≥10% among those with baseline CAC ≥100. We used linear regression to estimate the cognitive performance (z-standardized) with 95% CIs of each cognitive test by baseline CAC score (0 versus >0) and CAC progression.

RESULTS: Among the 2341 participants (mean baseline age 40.3±3.6 years; 56% female), baseline CAC >0 (9%) was associated with lower processing speed, verbal memory, and global cognition, whereas CAC progression (26%) was associated with lower processing speed and global cognition after adjusting for demographics, education, physical activity, depressive symptoms, APOE ε4 allele, and baseline CAC score. The standardized cognitive differences (95% CI) for CAC progression versus no progression were -0.14 (95% CI, -0.23 to -0.06) for the digit symbol substitution test and -0.09 (95% CI, -0.17 to -0.01) for the Montreal cognitive assessment.

CONCLUSIONS: CAC progression was associated with worse midlife processing speed and global cognition, independent of baseline CAC score and established risk factors. Repeated CAC assessments may offer clinical value for identifying individuals at increased risk for midlife cognitive decline.

PMID:41693559 | DOI:10.1161/CIRCOUTCOMES.125.012646