Midlife subclinical atherosclerosis and cardiovascular risk factors linked to hypometabolism in Alzheimer’s disease relevant regions

Abstract

Background: Atherosclerosis has been linked to cognitive decline in late life; however, the impact of cardiovascular risk factors (CVRFs) and subclinical atherosclerosis on brain metabolism at earlier stages remains unexplored.Method: This study, aimed at determining the association between brain metabolism, subclinical atherosclerosis and CVRFs in midlife, included 547 asymptomatic middleaged participants (50±4 years, 82% men) from the Progression of Early Subclinical Atherosclerosis study with evidence of subclinical atherosclerosis. Participants underwent 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). Global brain FDG uptake and voxel-wise analyses were used to evaluate the associations of cerebral metabolism with CVRFs and atherosclerotic plaque burden in carotids and femorals assessed by 3D-vascular ultrasound.Result: Global FDG uptake showed an inverse correlation with 30-year Framingham Risk Score (30y-FRS) (β=-0.15, p<0.001). This association was mainly driven by the presence of hypertension (d=0.36, p<0.001). Carotid plaque burden was inversely associated with global brain FDG uptake (β=-0.16, p<0.001), even after adjusting for 30y-FRS. Voxel-wise approaches revealed that the brain areas most strongly affected by hypometabolism in association with 30y-FRS, hypertension, and carotid plaque burden were parietotemporal regions (angular, supramarginal, and inferior/middle temporal gyri) and the cingulate gyrus. Conclusion:In asymptomatic middle-aged individuals, cardiovascular risk is associated with brain hypometabolism, with hypertension being the modifiable CVRF showing the strongest association. Subclinical carotid plaque burden is also linked to reduced brain metabolism independently of CVRFs. Cerebral areas showing hypometabolism