Brain's Metabolic Run-up to Dementia Directly Linked to Hype
What could be early metabolic signs of future dementia, as seen by PET, were closely associated with standard cardiovascular (CV) disease risk factors, some modifiable, in a study of middle-aged people in the community.

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.

This study sought to determine the association between brain metabolism, subclinical atherosclerosis, and CVRFs in middle-aged asymptomatic individuals.

This study included 547 asymptomatic middle-aged participants (50 ± 4 years, 82% men) from the PESA (Progression of Early Subclinical Atherosclerosis) study with evidence of subclinical atherosclerosis. Participants underwent 18F-fluorodeoxyglucose (FDG)-positron emission tomography. 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 3-dimensional vascular ultrasound.

-- Global FDG uptake showed an inverse correlation with 30-year Framingham Risk Score (FRS).

-- This association was mainly driven by the presence of hypertension.

-- Carotid plaque burden was inversely associated with global brain FDG uptake, even after adjusting for 30-year FRS.

-- Voxel-wise approaches revealed that the brain areas most strongly affected by hypometabolism in association with 30-year FRS, hypertension, and carotid plaque burden were parietotemporal regions (angular, supramarginal, and inferior/middle temporal gyri) and the cingulate gyrus.

Conclusively, 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 include those known to be affected in dementia. These data reinforce the need to control CVRFs early in life in order to potentially reduce the brain’s midlife vulnerability to future cognitive dysfunction.