Projects

T.

Examining a dose-dependent exercise intervention on cerebrovascular plasticity in late adulthood

Aerobic exercise (AE) is one of the most promising, accessible, and cost-effective methods for reducing risk for Alzheimer’s disease and related dementias, and is highly expected to improve brain health and cognition in older adults. However, we do not fully understand the mechanism by which AE-induced changes in the brain improve cognition and reduce the likelihood of transitioning to cognitive impairment. Cerebrovascular alterations progress with aging and have been identified as one of the primary factor that associated with cognitive decline. Therefore, one leading hypothesis is that AE can modify aging-associated cerebrovascular deteriorations by accumulating long-term adaptations through repeated training sessions. These cerebrovascular changes could mediate improvements in structure and function in the brain, and associate with cognitive improvement. However, we still do not fully understand the mechanisms by which it works, nor the most effective doses to maximize cerebrovascular improvements. In this study, we assess cerebrovascular changes and their relationship with structural and functional brain changes in response to an AE intervention, we test whether a 12-month RCT of AE modifies cerebrovascular pulsatility and blood flow and whether these changes mediate improvements in cognition,  whether AE-induced cerebrovascular changes mediate improvements in brain atrophy, functional connectivity, and lessen WMH growth. We will also test whether any effects are associated with pre-existing health status, such as hypertension and type2 diabetes, which are associated with risk for AD/ADRD and linked to AD pathology (e.g. Ab and tau). 

Technical developments of cerebrovascular function and structure  

• cerebral pulsatility 

Understanding the mechanism of neurovascular regulation

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Functional MRI has revolutionized our understanding of the human brain. However, the source of widely using blood-oxygen-level-dependent (BOLD) signals are still unclear. Using the developed method mentioned above, multiple cerebrovascular metrics were effectively measured for the brain functional changes. CBVa responses are better localized to neural activation compared to BOLD responses and CBVa changes dominate the total blood volume changes during neural activation. Rapid arterial dilation is followed by slow venous dilation during brain activation. This suggests a contribution of venous blood volume changes to the BOLD signals is significant when the stimulation duration is long but not short. The transit time and CBVa are found as early indicators of cerebrovascular impairment compared with widely used CBF. These works had a tremendous impact in the functional MRI field by providing guidance for interpretation of BOLD signal changes and better understanding of neurovascular coupling during brain activation.  

Development of MRI techniques for functional MRI and arterial spin labeling

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Significant distortion and signal dropout from high susceptible regions were improved by MRI technical development. This significantly improved temporal signal to noise ratio and BOLD signal in high-susceptibility brain regions, such as temporal and prefrontal regions. Methods were developed to effectively measure multiple cerebrovascular metrics for the brain physiological changes. These enabled the entire brain to be evaluated with high temporal resolution by effectively overcoming the limitations in slice coverage due to finite transit times. With this approach, detailed assessment of cerebrovascular regulation across whole brain enables better characterization of altered cerebrovascular physiology.

Hippocampal vascular supply and its mediating role in systemic physiological influence on hippocampal volume.

- The interplay of systemic vascular inflammation, autonomic dysfunction, and metabolic disturbances converges through multiple pathways, with hippocampal supply vessel velocity serving as a critical mediator that indirectly influences hippocampal structural integrity.