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

- Cerebrovascular reactivity (CVR) was examined in relation to vascular risk factors (VRF).
- CVR was compared in brain regions underlying the default-mode network vs non-DMN.
- CVR was lower for DMN regions relative to non-DMN regions in those with VRF.
- CVR may represent an important preclinical marker for brain health in later life.

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 50.4 years) 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.