Vascular risk factors, cerebrovascular reactivity, and the default-mode brain network

Abstract

Cumulating evidence from epidemiologic studies implicates cardiovascular health and cerebrovascular function in several brain diseases in late life. We examined vascular risk factors with respect to a cerebrovascular measure of brain functioning in subjects in mid-life, which could represent a marker of brain changes in later life. Breath-hold functional MRI (fMRI) was performed in 541 women and men (mean age 50.4years) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study. Cerebrovascular reactivity (CVR) was quantified as percentage change in blood-oxygen level dependent (BOLD) signal in activated voxels, which was mapped to a common brain template and log-transformed. Mean CVR was calculated for anatomic regions underlying the default-mode network (DMN) – a network implicated in AD and other brain disorders – in addition to areas considered to be relatively spared in the disease (e.g. occipital lobe), which were utilized as reference regions. Mean CVR was significantly reduced in the posterior cingulate/precuneus (β=−0.063, 95% CI: −0.106, −0.020), anterior cingulate (β=−0.055, 95% CI: −0.101, −0.010), and medial frontal lobe (β=−0.050, 95% CI: −0.092, −0.008) relative to mean CVR in the occipital lobe, after adjustment for age, sex, race, education, and smoking status, in subjects with pre-hypertension/hypertension compared to normotensive subjects. By contrast, mean CVR was lower, but not significantly, in the inferior parietal lobe (β=−0.024, 95% CI: −0.062, 0.014) and the hippocampus (β=−0.006, 95% CI: −0.062, 0.050) relative to mean CVR in the occipital lobe. Similar results were observed in subjects with diabetes and dyslipidemia compared to those without these conditions, though the differences were non-significant. Reduced CVR may represent diminished vascular functionality for the DMN for individuals with prehypertension/hypertension in mid-life, and may serve as a preclinical marker for brain dysfunction in later life.