Association of Cardiac Biomarkers With Structural Brain Changes and Cognitive Impairment

Cardiovascular disease is linked to an increased risk of dementia. The aim of this study was to evaluate whether blood-based cardiac biomarkers are associated with structural brain changes and cognitive impairment and to explore whether structural brain changes mediate alterations in cognitive function. We included participants from the population-based Hamburg City Health Study, recruiting citizens between 45 and 74 years of age. High-sensitivity cardiac troponin I (hs-cTnI), midregional pro-atrial natriuretic peptide, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations were measured. From brain MRI, we quantified markers of neurodegeneration (total brain volume, cortical thickness), markers of vascular brain damage (white matter hyperintensity volume, peak width of skeletonized mean diffusivity [PSMD]), and measures of structural brain network organization. Cognitive function was assessed using subtests of the CERAD-Plus battery. We applied multivariable-adjusted linear regression analyses and structural equation modeling to investigate the association of cardiac biomarkers with structural brain changes and cognitive function. The analysis included 2,553 participants with a median age of 64 years, and 44% were women. Higher levels of natriuretic peptides were associated with imaging markers of neurodegeneration and vascular brain damage, for example, higher levels of NT-proBNP with lower cortical thickness (β = -0.081; 95% CI [-0.127 to -0.034]) and higher PSMD (β = 0.112; 95% CI [0.069-0.155]). Higher levels of hs-cTnI were associated with markers of vascular brain damage only, for example, with higher PSMD (β = 0.103; 95% CI [0.060-0.146]). All cardiac biomarkers studied were associated with alterations of structural brain connectivity reflecting changes in brain network organization toward less integration and more segregation. Elevated NT-proBNP was associated with lower scores in tests of verbal memory (β = -0.054; 95% CI [-0.100 to -0.008]) and verbal fluency (β = -0.054; 95% CI [-0.101 to -0.008]). In structural equation modeling, there was a significant effect of NT-proBNP on cognitive function mediated by structural brain changes. Monitoring cardiac biomarkers, especially NT-proBNP, may provide a low-invasive and widely available method to assess cognitive risk and potentially guide early preventive interventions. Longitudinal studies are needed to establish causality and explore the observed associations over time. ClinicalTrials.gov number, NCT03934957.