Poorer cerebrovascular reactivity in cognitively intact individuals with APOE4 detected using resting state BOLD-fMRI

Motivation: Cerebrovascular reactivity (CVR) is reduced in apolipoprotein E4 (APOE4) carriers with Alzheimer's disease (AD), but its association with APOE4 carriers without cognitive impairment is less understood. Goal(s): This study aimed to investigate the impact of APOE4 status on CVR in individuals with a family history of AD and assess sex differences. Approach: CVR was measured using resting-state fMRI without respiratory challenges. Results: Our results revealed significantly lower relative CVR in individuals with APOE4 carriers in the cortical gray matter, temporal gyrus, insula, and cingulate gyrus. Males with APOE4 were found to be especially impacted in temporal areas. Impact: These findings suggest that individuals without cognitive impairment who carry the APOE4 genotype present lower cerebrovascular reactivity in multiple gray matter regions compared to non-carriers. Cerebrovascular reactivity may be an early biomarker of cerebrovascular dysfunction in individuals with APOE4 alleles.