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Updated: Sep 11, 2025
Evaluation of the Cognitive Performance of Hypertensive Patients with Silent Cerebrovascular Lesions
Published on: April 23, 2021
A structural heart-brain axis mediates the association between cardiovascular risk and cognitive function
Akshay Jaggi1, Eleanor L S Conole2, Zahra Raisi-Estabragh3,4
1Facultat de Matemàtiques i Informàtica, Universitat de Barcelona, Barcelona, España.
Insights
Vascular disease risk impacts cognitive function. This study reveals how heart and brain structure variations mediate this link, supporting the structural-functional model and identifying key imaging biomarkers.
Area of Science:
- Cardiovascular and Neurological Sciences
- Medical Imaging and Biomarkers
Background:
- Elevated vascular disease risk is linked to poorer cognitive function, but the underlying mechanisms remain unclear.
- The structural-functional model proposes that vascular risk leads to cardiac remodeling, causing chronic cerebral hypoperfusion and brain damage.
Purpose of the Study:
- To test the structural-functional model's prediction that heart and brain structural variations associate with vascular risk and cognitive function.
- To identify imaging biomarkers and explore 'heart-brain axes' that mediate the relationship between vascular risk and cognitive decline.
Main Methods:
- Analysis of a large UK Biobank cohort (N = 11,962) including vascular risk factors, cardiac MRI radiomics, and brain structural/diffusion MRI.
- Extraction and analysis of 'heart-brain axes' representing covariation between cardiac and brain structural measures.
- Assessment of cognitive function using standardized tests.
Main Results:
- Several heart (e.g., left ventricular end-diastolic volume) and brain (e.g., grey matter volume) measures partially explained the vascular risk-cognitive function association.
- A specific 'heart-brain axis' (lower myocardial intensity, lower grey matter volume, poorer thalamic white matter integrity) fully mediated this association.
- Brain structural variations did not entirely explain the association between heart structure and cognitive function, suggesting a more complex relationship.
Conclusions:
- Findings provide evidence supporting the structural-functional hypothesis linking vascular risk, cardiac remodeling, and cognitive function.
- Identified novel imaging biomarkers and 'heart-brain axes' that elucidate the relationship between cardiovascular health and brain function.
- Generated new hypotheses regarding the intricate pathways through which cardiovascular risk influences cognitive decline.
Abstract:
Elevated vascular disease risk associates with poorer cognitive function, but the mechanism for this link is poorly understood. A leading theory, the structural-functional model argues that vascular risk may drive adverse cardiac remodelling, which, in turn, leads to chronic cerebral hypoperfusion and subsequent brain structural damage. This model predicts that variation in heart and brain structure should associate with both greater vascular risk and lower cognitive function. This study tests that prediction in a large sample of the UK Biobank (N = 11,962). We assemble and summarise vascular risk factors, cardiac magnetic resonance radiomics, brain structural and diffusion MRI indices, and cognitive assessment. We also extract "heart-brain axes" capturing the covariation in heart and brain structure. Many heart and brain measures partially explain the vascular risk-cognitive function association, like left ventricular end-diastolic volume and grey matter volume. Notably, a heart-brain axis, capturing correlation between lower myocardial intensity, lower grey matter volume, and poorer thalamic white matter integrity, completely mediates the association, supporting the structural-functional model. Our findings also complicate this theory by finding that brain structural variation cannot completely explain the heart structure-cognitive function association. Our results broadly offer evidence for the structural functional hypothesis, identify imaging biomarkers for this association by considering covariation in heart and brain structure, and generate novel hypotheses about how cardiovascular risk may link to cognitive function.
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