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bioRxiv · 10.1101/2025.06.02.657532

The Impact of Coronary Artery Disease on Brain Vascular and Metabolic Health: Links to Cognitive Function

Sanami, S.·Tremblay, S. A.·Rezaei, A.·Potvin-Jutras, Z.·Sabra, D.·Intzandt, B.·Gagnon, C.·Mainville-Berthiaume, A.·Wright, L.·Gayda, M.·Iglesies-Grau, J.·Nigam, A.·Bherer, L.·Gauthier, C.
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Abstract

BackgroundCoronary artery disease (CAD) is the leading cause of mortality worldwide and is associated with an increased incidence of cognitive decline, however the pathological mechanisms linking CAD to brain and cognitive health remain unclear. Prior research has identified regional deficits in cerebral blood flow (CBF) and cerebrovascular reactivity (CVR), a measure of vascular reserve, in patients with CAD. However, the impact of these cerebrovascular deficits on cognition has not been explored, nor has the effect of CAD on cerebral metabolic health. This study aims to fill these gaps by investigating how CAD influences cerebral vascular and metabolic health, and how these alterations relate to cognitive function across multiple domains. MethodsQuantitative magnetic resonance imaging (MRI) was employed to measure a comprehensive profile of cerebral vascular and metabolic health, including CBF, CVR, cerebral metabolic rate of oxygen (CMRO2), and oxygen extraction fraction (OEF). Cognition was assessed using a validated neuropsychological battery from which composite scores were extracted, reflecting executive functions, working memory, processing speed, and verbal episodic memory. ResultsA total of 35 patients with CAD and 37 healthy controls were included in the final analysis. Patients with CAD demonstrated widespread impairments in both cerebral vascular and metabolic health, characterized by lower CBF, CVR, and CMRO2, and increased OEF, indicative of insufficient oxygen delivery. Notably, lower CVR was associated with poorer executive function, suggesting a specific role of vascular reserve for preserving executive functions. Furthermore, higher OEF was associated with poorer working memory, showing the importance of preserved oxygen consumption for maintaining cognitive function. ConclusionThis study reveals that CAD is associated with impaired cerebral vascular and metabolic health, providing a pathological basis for cognitive decline. Specifically, reduced CVR and elevated OEF emerged as sensitive biomarkers linking impaired brain health and cognition. These markers hold promise for guiding future interventions aimed at preserving cognitive health in patients with CAD. Clinical PerspectiveO_ST_ABSWhat Is New?C_ST_ABSO_LICoronary artery disease is associated with an increased incidence of cognitive decline but the biological mechanisms underlying these changes in cognition are unclear. C_LIO_LIThis is the first study to comprehensively demonstrate profound and widespread deficits in both cerebral vascular and oxidative metabolic health in patients with coronary artery disease. C_LIO_LICerebrovascular reactivity and oxygen extraction fraction may be sensitive biomarkers of early cognitive decline in coronary artery disease. C_LI What Are the Clinical Implications?O_LIThe widespread impairments in cerebral vascular and metabolic health suggest that coronary artery disease has profound consequences on the brain. C_LIO_LIPoor vascular reserve and an imbalance between oxygen delivery and usage may be crucial determinants of cognitive health. These results highlight the limitations of traditional biomarkers in understanding the brains vulnerability and the need for these novel and quantitative biomarkers of cerebral physiological health. C_LIO_LIThese findings suggest that cerebral vascular and metabolic deficits exist even in the absence of overt cognitive decline in coronary artery disease, emphasizing the need for early detection and preventative strategies. C_LI

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Sanami, S., Tremblay, S. A., Rezaei, A., Potvin-Jutras, Z., Sabra, D., Intzandt, B., Gagnon, C., Mainville-Berthiaume, A., Wright, L., Gayda, M., Iglesies-Grau, J., Nigam, A., Bherer, L., Gauthier, C.. 2025-06-06. The Impact of Coronary Artery Disease on Brain Vascular and Metabolic Health: Links to Cognitive Function. https://doi.org/10.1101/2025.06.02.657532

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