Multi-Modal Imaging Assessment of Neurovascular Uncoupling in Alzheimer's Disease and Related Dementia

Motivation: Alzheimer's disease (AD) is the fifth-leading cause of death in the USA, with treatment options hampered by insensitive early diagnostics. Goal(s): To develop a sensitive and stage specific diagnostic to identify regional alterations in neurovascular and metabolic regulation across the AD spectrum. Approach: Retrospective multi-modal ASL-MRI and 18F-FDG PET were assessed for regional neurovascular and metabolic dysregulation across the AD spectrum described previously1, 2. Results: AD animal models showed regional and stage dependent dysregulation1, 2, which was replicated in the current clinical study. MCI regions showed Type 1 and Type 2 uncoupling1, 2, while AD regions displayed prodromal and neuro-metabolic failure phenotypes. Impact: Early diagnosis in AD is critical to develop a prophylactic treatment strategy, minimize morbidity, and mitigating healthcare financial burden. Our novel analytical method permits early non-invasive detection of regional neurovascular and metabolic dysregulation suitable for clinical staging and enrolment.