Clinically feasible functional MRI providing independent assessments of cerebrovascular stiffness and microcirculation in typical aging and Alzheimer's Disease cohorts

PROJECT SUMMARY/ABSTRACT Alzheimer’s disease (AD) is the leading cause of dementia worldwide currently affecting over 50 million people. The pathophysiology of Alzheimer’s dementia is complex and multifactorial, however, decreases in cerebrovascular function have been linked to disease progression. Despite the role vascular health plays in the prognosis of AD, the ability to assess intracranial vascular integrity is limited. There is a critical need to assess vascular properties sensitive to microvascular function and arterial stiffness to understand why and how vascular health is a substantial risk factor for AD dementia. The right tool will be able to assess multiple cerebrovascular health metrics and monitor potential interventions targeting the vascular system in the treatment of AD dementia. This study aims to utilize a conventional resting-state functional MRI (rs-fMRI) scan to assess arterial stiffness and microvascular health through the development and implementation of specialized image processing techniques. These metrics will be applied to two large datasets available from the Human Connectome Project (HCP) – Aging and the Indiana Alzheimer’s Disease Research Center (IADRC). Using the HCP dataset, we will assess vascular changes in a typically aging sample (aims 1 & 2). With the IADRC dataset, we will assess the associations of cerebrovascular health with cognitive function across a spectrum of cognitive impairment (aim 3). The central hypothesis is that measures sensitive to arterial stiffness and microvascular function derived from specialized rs-fMRI image processing will significantly correlate with typical aging and cognitive impairment in the spectrum of AD pathology. The central hypothesis will be tested with the following aims: Aim 1: Assess the correlation of cerebral artery stiffness and age using rs-fMRI-derived arterial pulse propagation mapping. Aim 2: Evaluate rs-fMRI-derived cerebral transit time (CTT) in the HCP-aging dataset. Aim 3: Determine whether rs-fMRI-derived arterial stiffness and CTT in the AD-spectrum are significantly associated with cognitive impairment. The measures of arterial stiffness and microvascular function will provide greater insight into the influence of vascular health on AD dementia and may be used in the future to monitor intervention status. The entire pipeline with detailed demo code developed in this project will be openly shared to allow other researchers to extract these vascular metrics from standard rs-fMRI data and study other pathologies with known cerebrovascular involvement, resulting in a high clinical impact.