(FE-BBB) Eliciting the Role of Vascular Wall Dysfunction in Alzheimer’s Disease

Cardiovascular disease, as well as cerebrovascular (CV) disease, has a strong link with both mild cognitive impairment and dementia; however, the question of whether CV pathology modulates underlying pathophysiology of Alzheimer’s disease (AD) remains an unanswered question despite years of research because the requisite methods to fully address this have not existed until now. There remain many questions regarding CV disease/AD pathophysiology interactions and whether related clinical AD dementia is enhanced by CV disease that are now addressable at UW by pairing the most cutting edge MRI methods with biomarker confirmed older adults who are in the AD continuum (amyloid positive) and who range in clinical stage from unimpaired to dementia.
To provide insights into AD relationships, non-invasive Magnetic Resonance Imaging (MRI) has been utilized in longitudinal studies of AD risk-enriched populations. The current project goes far beyond clinically available MRI techniques, which lack sensitivity and specificity to address key vascular hypotheses in AD studies. MRI methods commonly employed today such as fluid attenuation and susceptibility imaging only indirectly measure CV pathology and cannot inform on the vascular wall dysfunction that is hypothesized to aid in AD related pathology. To address these gaps, the overarching objective of this project is to characterize cerebrovascular involvement in AD through the investigation of a novel battery of non-invasive, MRI-based measures of cerebrovascular health, specifically measures of blood brain barrier (BBB) permeability (with advanced diffusion-prepared arterial spin labelling [dASL]) and arterial wall stiffening using innovative 4D-Flow approaches. In this study, we will evaluate feasibility of these advanced MRI techniques in a control group followed by studies in both cognitively normal, CSF confirmed amyloid positive and amyloid negative subjects.