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

Lower hippocampal CVR was associated with lower left hippocampal volume in older adults at Wave 2.

• 163 participants from the Heart and Brain Study received multimodal MRI scans.
• CVR was measured using BOLD fMRI with a 5% CO2 inhalation challenge at Wave 2.
• Wave 2 assessments occurred between 2019-2023 with a mean age of 76.9 years (SD 4.5).
• The association was specific to the left hippocampal volume in cross-sectional analysis.
• Linear regression was used to examine cross-sectional associations.

Lower hippocampal CVR was associated with lower fractional anisotropy and higher mean, radial, and axial diffusivity in white matter tracts at Wave 2.

• Affected tracts included the corpus callosum, internal capsule, and fornix.
• These associations were cross-sectional, measured at Wave 2 (mean age 76.9 years, SD 4.5).
• Diffusion tensor imaging was used to assess white matter microstructural integrity.
• Higher mean, radial, and axial diffusivity alongside lower fractional anisotropy indicate reduced white matter integrity.

Lower hippocampal CVR was associated with greater longitudinal changes in white matter microstructural integrity between Waves 1 and 2.

• Wave 1 assessments occurred between 2012-2014 (mean age 68.2 years, SD 4.4).
• Wave 2 assessments occurred between 2019-2023 (mean age 76.9 years, SD 4.5), representing approximately 8 years of follow-up.
• Affected tracts for longitudinal changes included the corpus callosum, internal capsule, and cingulum bundle.
• CVR was only measured at Wave 2, so directionality of the association with longitudinal white matter changes cannot be confirmed.

There were no significant associations between hippocampal CVR and white matter hyperintensities.

• White matter hyperintensities were assessed using fluid-attenuated inversion recovery (FLAIR) imaging.
• This null finding applied to both cross-sectional and longitudinal analyses.
• The absence of association suggests hippocampal CVR may be more closely linked to microstructural than macrostructural white matter changes.

The study used a multimodal MRI protocol in 163 older adults from the Heart and Brain Study across two waves of data collection approximately 8 years apart.

• Modalities included T1-weighted structural imaging, diffusion tensor imaging, FLAIR imaging, and BOLD fMRI.
• Wave 1 took place 2012-2014 (mean age 68.2, SD 4.4 years) and Wave 2 took place 2019-2023 (mean age 76.9, SD 4.5 years).
• CVR measurement via 5% CO2 inhalation challenge was administered only at Wave 2.
• Linear regression was the primary statistical method for both cross-sectional and longitudinal analyses.