Novel imaging and endothelial biomarkers of small vessel cerebrovascular disease

Small vessel cerebrovascular disease and Alzheimer’s disease are the two most common causes of cognitive decline in the elderly, but methods for determining the relative contributions of both these pathologies to functional impairment, understanding their interactions, predicting progression and defining targets for clinical trials remain underdeveloped. The overarching goal of this proposal is to further develop novel neuroimaging and serologic biomarkers of cerebrovascular disease. Accomplishing this goal will improve early detection, diagnosis, and prognosis of small vessel cerebrovascular disease in older subjects, and provide better targets and outcome metrics for clinical trials. We propose to longitudinally study 400 well characterized older subjects from ongoing projects at UCSF and UCD who present with a range of cerebrovascular burden and functional decline. Our search for biomarkers will focus on novel neuroimaging variables and measures of endothelial dysfunction. Our aims will address the relationships between these markers and measures of amyloid burden, cognition, and change over time.
 

Cerebral small vessel disease (CVD) can cause memory or thinking problems that often lead to dementia. CVD affects small blood vessels in the brain, like arteries and capillaries, which are important for moving oxygen and nutrients to cells in the brain. Investigators wanted to study how cerebral small vessel disease might impact cognitive decline in adults. In order to improve understanding of early detection or potential treatments that might reduce the impact of small vessel disease, investigators explored several different biomarkers which might later provide better diagnostic tools for small vessel disease. In the course of this project, investigators at UC Davis, UCSF, and UCLA used data from over 400 subjects to better understand certain potential biomarkers for small vessel disease. The findings from this study included: - White matter hyperintensity was found to be an indicator of vascular brain injury, and was associated with vascular risk and disease, as well as cognitive impairment. - Specific MRI-related imaging biomarkers, such as diffusion tensor imaging biomarkers or free water, were found to sensitively measure cognitive decline in a variety of individuals. These biomarkers are noninvasive and the technology involved is widely available. - Blood-based biomarkers, such as plasma endothelial signaling and plasma endothelial inflammation, are accurate and sensitive to vascular contributions to cognitive impairment. These biomarkers can also be used in the future to identify vulnerable populations who are at risk for progressive vascular contributions to cognitive impairment and dementia.
 
Project End Date 28-September-2021