The Relationship Between Hippocampal Cerebrovascular Reactivity and Brain Structure in Older Age

Cerebral autoregulatory mechanisms such as cerebrovascular reactivity (CVR) are impaired in dementia. However, their associations with brain structure, especially in the hippocampus, remain unclear. We investigated associations between hippocampal CVR and hippocampal volume, white matter microstructural integrity, and white matter hyperintensities in older adults. 163 participants from the Heart and Brain Study received multimodal MRI scans, including T1-weighted structural imaging, diffusion tensor imaging, fluid-attenuated inversion recovery imaging at Wave 1 (2012-2014, mean age 68.2, SD 4.4 years) and Wave 2 (2019-2023, mean age 76.9, SD 4.5 years). Participants also received BOLD fMRI scans with a 5% CO₂ inhalation challenge to measure CVR at Wave 2. Linear regression was used to examine the cross-sectional associations of hippocampal CVR with brain structure at Wave 2 as well as with changes in brain structure between Waves 1 and 2. Lower hippocampal CVR was associated with lower left hippocampal volume, as well as lower fractional anisotropy, higher mean, radial, and axial diffusivity in the corpus callosum, internal capsule, and fornix at Wave 2. Lower hippocampal CVR was also associated with greater changes in white matter integrity in the corpus callosum, internal capsule, and cingulum bundle between Waves 1 and 2. There were no significant associations between hippocampal CVR and white matter hyperintensities. Our findings highlight hippocampal CVR as a potential imaging marker associated with structural brain changes relevant to cognitive decline. Further longitudinal studies are needed to clarify the directionality of this association.