Vascular and glymphatic dysfunction as drivers of cognitive impairment in Alzheimer's disease: Insights from computational approaches

Abstract

Alzheimer's disease (AD) is driven by complex interactions between vascular dysfunction, glymphatic system impairment, and neuroinflammation. Vascular aging, characterized by arterial stiffness and reduced cerebral blood flow (CBF), disrupts the pulsatile forces necessary for glymphatic clearance, exacerbating amyloid-beta (Aβ) accumulation and cognitive decline. This review synthesizes insights into the mechanistic crosstalk between these systems and explores their contributions to AD pathogenesis. Emerging machine learning (ML) tools, such as DeepLabCut and Motion sequencing (MoSeq), offer innovative solutions for analyzing multimodal data and enhancing diagnostic precision. Integrating ML with imaging and behavioral analyses bridges gaps in understanding vascular-glymphatic dysfunction. Future research must prioritize these interactions to develop early diagnostics and targeted interventions, advancing our understanding of neurovascular health in AD. © 2025