Abstract 149: Metabolic Neuroimaging in the Assessment of Cardiovascular Risk: A Regional FDG‐PET Analysis
Authors: Subtirelu Robert C. , Teichner Eric M. , Su Yvonne , Werner Thomas , Alavi Abass , Høilund‐Carlsen Poul Flemming , Revheim Mona‐Elisabeth 
Published: March 2024

Introduction
Emerging evidence suggests a robust association between cardiovascular disease (CVD) and cognitive decline, accentuating the necessity for early detection and intervention. 18F‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) has proven efficacious in identifying metabolic neurological changes at a molecular level, even before conventional imaging methods can detect structural changes. This study analyzed regional glucose metabolism in individuals with known CVD risk factors. The detection of such metabolic changes could assist in determining the necessity and timing of vascular interventions, such as carotid endarterectomy (CEA) or carotid artery angioplasty with stenting (CAS), contributing to improved patient outcomes and reduced postoperative complications.

Methods
We compared 79 healthy controls (mean age 44.5 ± 13.8 years, 53.2% males) and 40 individuals (mean age 55.9 ± 11.9 years, 50% males) at increased risk for cardiovascular disease (CVD) as assessed by the systematic coronary risk evaluation tool. All subjects were grouped into two age‐matched cohorts: younger (<45 years) and older (≥45 years). All subjects underwent whole‐body FDG‐PET/CT imaging. The quantitative regional analysis of PET images was performed using MIMneuro version 7.1.5 (MIM Software, Inc., Cleveland, Ohio). 70 neurological structures were analyzed in each subject. An independent samples t‐test was used to assess the differences in z‐scores between controls and at‐risk subjects. The threshold for significance was set at P < 0.05.

Results
Within the younger cohort, the cingulate gyrus (p=0.0206) and the anterior cingulate gyrus (p=0.0348) demonstrated significant hypometabolism in patients with known cardiac risk factors when compared to healthy controls. Within the older cohort, the supplementary motor area demonstrated significant hypometabolism (p=0.0145), while both the pons (p=0.0169) and pontine tegmentum (p=0.0063) had significant hypermetabolism in patients with known cardiac risk factors when compared to healthy controls.

Conclusion
Our analysis revealed an inverse relationship between increased cardiovascular disease risk and metabolic activity, particularly in three brain regions: the cingulate gyrus, the anterior cingulate gyrus, and the supplementary motor area. The findings substantiate the vulnerability of the cingulate gyrus to the impacts of small vessel disease. Hypoperfusion, a potential consequence of atherosclerotic plaque accumulation in the perfusing artery, engenders a pernicious cycle of hypoxia, oxidative stress, mitochondrial dysfunction, and inflammation, which exacerbates neuronal cell death. The cingulate gyrus, vascularized by the pericallosal arteries (branches of the anterior cerebral artery from the internal carotid arteries), and the pontine tegmentum, supplied by branches of the basilar artery, are pivotal in this context. Calcification within these arteries could potentially instigate decreased perfusion, thereby contributing to the observed hypometabolism. Examining microstructural and functional changes in the neurovascular system in response to cardiovascular disease risk factors provides key insights. These findings could inform targeted interventions, streamline perioperative strategies, and aid in decision‐making regarding the timing of vascular interventions. Future studies investigating the association among arterial calcification, regional hypometabolism, and cognitive decline may provide a deeper understanding of the complex interplay between cardiovascular health and cognitive function, supporting the improvement of intervention strategies and refinement surgical techniques.