Jensen Märit, Vettorazzi Eik, Weber Philipp, Petersen Marvin, Schell Maximilian, Nägele Felix Leonard, Link Moritz Andreas, Schlemm Eckhard, Rimmele David Leander, Becher Peter Moritz, Cheng Bastian, Blankenberg Stefan, Kirchhof Paulus, Zeller Tanja, Twerenbold Raphael, Thomalla Götz
Department of Neurology, University Medical Center Hamburg-Eppendorf, Germany.
German Centre for Cardiovascular Research (DZHK e.V.), Partner Site Hamburg/Kiel/Lübeck.
Neurology. 2025 Aug 12;105(3):e213865. doi: 10.1212/WNL.0000000000213865. Epub 2025 Jul 3.
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.
心血管疾病与痴呆风险增加有关。本研究旨在评估血液中的心脏生物标志物是否与脑结构改变和认知障碍相关，并探讨脑结构改变是否介导认知功能的变化。
我们纳入了基于人群的汉堡城市健康研究的参与者，招募年龄在45至74岁之间的市民。测量了高敏心肌肌钙蛋白I（hs-cTnI）、中段心房利钠肽原和N末端B型利钠肽原（NT-proBNP）的浓度。通过脑磁共振成像（MRI），我们量化了神经退行性变的标志物（全脑体积、皮质厚度）、脑血管损伤的标志物（白质高信号体积、骨架化平均扩散率峰值宽度[PSMD]）以及脑结构网络组织的测量指标。使用CERAD-Plus成套测试的子测试评估认知功能。我们应用多变量调整线性回归分析和结构方程模型来研究心脏生物标志物与脑结构改变和认知功能之间的关联。
分析纳入了2553名参与者，中位年龄为64岁，44%为女性。利钠肽水平升高与神经退行性变和脑血管损伤的影像学标志物相关，例如，NT-proBNP水平升高与皮质厚度降低（β=-0.081；95%可信区间[-0.127至-0.034]）和PSMD升高（β=0.112；95%可信区间[0.069-0.155]）相关。hs-cTnI水平升高仅与脑血管损伤的标志物相关，例如与PSMD升高相关（β=0.103；95%可信区间[0.060-0.146]）。研究的所有心脏生物标志物均与脑结构连接性改变相关，反映脑网络组织向整合减少和分离增加的变化。NT-proBNP升高与言语记忆测试（β=-0.054；95%可信区间[-0.100至-0.008]）和言语流畅性测试（β=-0.054；95%可信区间[-0.101至-0.008]）得分较低相关。在结构方程模型中，NT-proBNP通过脑结构改变对认知功能有显著影响。
监测心脏生物标志物，尤其是NT-proBNP，可能提供一种低侵入性且广泛可用的方法来评估认知风险，并可能指导早期预防性干预。需要进行纵向研究以确定因果关系并随着时间推移探索观察到的关联。
ClinicalTrials.gov编号，NCT03934957。
