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The Relationship Between Hippocampal Cerebrovascular Reactivity and Brain Structure in Older Age
Congxiyu Wang1,2, Lucy Jobbins3, Graham Reid4,5
1Department of Psychiatry, University of Oxford, Oxford, UK.
Insights
Lower hippocampal cerebrovascular reactivity (CVR) is linked to reduced hippocampal volume and white matter integrity in older adults. This suggests CVR may be an imaging marker for age-related brain changes and cognitive decline.
Area of Science:
- Neuroimaging
- Cerebrovascular Physiology
- Aging Brain
Background:
- Cerebral autoregulatory mechanisms, like cerebrovascular reactivity (CVR), are crucial for brain health but are often impaired in dementia.
- The relationship between hippocampal CVR and structural brain changes, particularly in the hippocampus and white matter, is not well understood in older adults.
Purpose of the Study:
- To investigate the associations between hippocampal CVR and hippocampal volume, white matter microstructural integrity, and white matter hyperintensities in an aging cohort.
- To explore cross-sectional and longitudinal associations between hippocampal CVR and brain structure over time.
Main Methods:
- 163 older adults from the Heart and Brain Study underwent multimodal MRI (T1-weighted, DTI, FLAIR) at two time points.
- BOLD fMRI with a 5% CO2 inhalation challenge was used to measure hippocampal CVR at Wave 2.
- Linear regression models examined associations between hippocampal CVR and brain structure (volume, white matter integrity, white matter hyperintensities) cross-sectionally and longitudinally.
Main Results:
- Lower hippocampal CVR was associated with reduced left hippocampal volume at Wave 2.
- Reduced white matter integrity (lower fractional anisotropy, higher diffusivity) in the corpus callosum, internal capsule, and fornix was linked to lower hippocampal CVR.
- Lower hippocampal CVR correlated with greater decline in white matter integrity in the corpus callosum, internal capsule, and cingulum bundle between study waves.
- No significant associations were found between hippocampal CVR and white matter hyperintensities.
Conclusions:
- Hippocampal CVR may serve as a valuable imaging biomarker for detecting structural brain changes associated with aging and cognitive decline.
- The findings underscore the link between cerebrovascular function and brain structure in the aging brain.
- Further longitudinal research is necessary to establish the causal relationship and directionality of these associations.
Abstract:
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.
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