Framingham Cardiovascular Risk Profile Correlates with Impaired Hippocampal and Cortical Vasoreactivity to Hypercapnia

Vascular risk factors affect cerebral blood flow (CBF) and cerebral vascular reactivity, contributing to cognitive decline. Hippocampus is vulnerable to both Alzheimer's disease (AD) pathology and ischemia; nonetheless, the information about the impact of vascular risk on hippocampal perfusion is minimal. Cognitively, healthy elderly (NL=18, 69.9±6.7 years) and subjects with mild cognitive impairment (MCI=15, 74.9±8.1 years) were evaluated for the Framingham cardiovascular risk profile (FCRP). All underwent structural imaging and resting CBF assessment with arterial spin labeling (ASL) at 3T magnetic resonance imaging (MRI). In 24 subjects (NL=17, MCI=7), CBF was measured after a carbon dioxide rebreathing challenge. Across all subjects, FCRP negatively correlated with hippocampal (ρ=-0.41, P=0.049) and global cortical (ρ=-0.46, P=0.02) vasoreactivity to hypercapnia (VR(h)). The FCRP-VR(h) relationships were most pronounced in the MCI group: hippocampus (ρ=-0.77, P=0.04); global cortex (ρ=-0.83, P=0.02). The FCRP did not correlate with either volume or resting CBF. The hippocampal VR(h) was lower in MCI than in NL subjects (Z=-2.0, P=0.047). This difference persisted after age and FCRP correction (F([3,20])=4.6, P=0.05). An elevated risk for vascular pathology is associated with a reduced response to hypercapnia in both hippocampal and cortical tissue. The VR(h) is more sensitive to vascular burden than either resting CBF or brain volume.