Age‐Related Variations in Cerebrovascular Reactivity Measured With Resting‐State BOLD MRI

Cerebrovascular reactivity (CVR) is a crucial physiological marker of vascular health and has been linked to aging-related cerebrovascular decline. Resting-state BOLD MRI-based relative CVR mapping (RS-rCVR) offers a noninvasive and compliance-friendly alternative to gas-challenge methods, making it suitable for lifespan studies. This study aimed to examine age-related differences in RS-rCVR among healthy adults using voxel-wise and region-of-interest (ROI) analyses. We prospectively recruited 54 healthy adults, including 27 younger (20-28 years, mean = 23.3 ± 3.4; 16 females) and 27 older (57-75 years, mean = 66.5 ± 5.3; 16 females) participants. Resting-state fMRI data were acquired using a T2*-weighted gradient-echo EPI sequence at 3T. RS-rCVR maps were generated by linear regression of the voxel-wise BOLD time series against the global BOLD signal and normalized to cerebellar gray matter. Group-level analyses included voxel-wise comparisons, histogram analyses, and ROI-based statistical tests. The distribution of RS-rCVR values significantly differed between age groups (Kolmogorov-Smirnov test: KS = 0.039, p < 0.001). Voxel-wise comparisons revealed age-related reductions in RS-rCVR in the medial frontal cortex, precuneus, and cuneus in older adults. In contrast, ROI-averaged RS-rCVR values showed no statistically significant group differences across frontal, temporal, and occipital cortices (p > 0.05). Effect size analysis indicated small to moderate differences in specific regions (e.g., occipital cortex: d = 0.441; parietal cortex: d = 0.430; frontal middle gyrus: d = 0.275), but negligible effects in others (e.g., cingulate cortex: d = 0.006). While voxel-wise RS-rCVR mapping detects spatially localized age-related reductions in cerebrovascular reactivity, ROI-based analysis may obscure these effects due to anatomical averaging. These findings underscore the spatial heterogeneity of cerebrovascular aging and support the utility of voxel-level RS-rCVR approaches in lifespan research.