Imaging Vascular Function in Normal Aging, MCI, and Mild Dementia

ABSTRACT This application aims to broaden the research expertise of Dr. Xu, who has a background in bioengineering, by delving into clinical research of neurodegenerative diseases. The goal is to support her pursuit of an independent research career focused on using advanced neuroimaging techniques to identify cognitive decline caused by vascular insults. It is increasingly recognized that cognitive decline in Alzheimer’s disease (AD) is influenced by factors beyond the plaques and tangles, including small vessel diseases. Vascular dysfunction seems to precede tissue atrophy resulting from neuronal degeneration, suggesting that measuring vascular function could insights into alternative pathologies contributing to early-stage cognitive dysfunction. Dr. Xu recently developed a non-invasive method of measuring arterial cerebral blood volume (CBVa) using the novel magnetic resonance imaging (MRI) technique called the Fourier transform-based (FT-) velocity-selective (VS) arterial spin labeling (ASL). In this proposed research, the FT-VS ASL will be applied to investigate the relationship between CBVa and cognitive function. To pursue this line of research, Dr. Xu will aim to bridge the gap between her engineering background and clinical dementia research through structured mentorship, acquiring clinical training from conferences and seminars, and conducting mentored research on the association between CBVa and cognitive function in individuals with mild cognitive impairment and mild dementia. The central hypothesis is that CBVa will be higher among those with MCI and mild dementia and higher CBVa will be associated with poorer cognitive performance. The hypothesis will be tested by pursuing three specific aims: (1) To refine the FT-VS ASL method for measuring CBVa. (2) To compare group differences in multi-compartment CBV (arterial vs total) among cognitively normal young and older (controls), individuals with MCI, and those with mild AD dementia. Additionally, to determine the cross-sectional association between CBVa and cognitive function in participants with normal cognition, MCI, and mild AD dementia. (3) To assess the association between longitudinal changes in cognitive function and CBVa. Upon completion of this research, the expected outcomes include the development of a robust non-invasive tool for quantifying regional CBVa. Furthermore, understanding the association between CBVa and cognitive function will shed light on the vascular contribution to dementia. These outcomes will form the foundation for a competitive R01 grant application, which will prepare Dr. Xu to become an independent investigator examining the merit of CBVa as a biomarker for dementia in a large cohort and comparing its efficacy with other biomarkers related to AD and related dementias (ADRD).