Small Vessel Disease Biomarkers to Improve Understanding of Vascular and Alzheimer’s Dementia

The goal of this project is to develop new imaging markers that advance understanding of cerebral small vessel disease in individuals with VCID and AD, with the potential to improve biomarkers and identify new therapeutic targets for multi-etiology dementia.

Alzheimer’s disease (AD) and cerebral small vessel disease (cSVD) are the most frequent causes of dementia; however, current therapies primarily target AD-related cognitive decline, limiting their effectiveness when both cSVD and AD are present. Due to a gap in available biomarkers, the separation and characterization of cSVD- and AD-related cognitive decline is challenging and incomplete. In this project, we will evaluate novel imaging markers to study cSVD in individuals with confirmed AD and comorbid cSVD, aiming to advance biomarkers and therapeutic targets for multi-etiology dementia.

We will apply ferumoxytol-enhanced MRI to VCID and AD. Ferumoxytol is a blood-pool contrast agent that enables vascular-specific imaging not achievable with conventional agents. This project will evaluate a novel protocol to quantify unique microvascular characteristics, addressing a biomarker gap in small vessel disease assessment.

This project will deliver a new MRI protocol for unique characterization of the cerebral microvasculature and will investigate potential vascular disease pathways in individuals with VCID and AD. These innovations will yield new biomarkers and inform clinical trial design by identifying potentially modifiable therapeutic targets for vascular disease in common mixed VCID and AD.