[MRI-Based Insights into the Connection Between Traumatic Brain Injury, Glymphatic Dysfunction, and Neurodegenerative...

Traumatic brain injury (TBI) is a recognized risk factor for dementia and other neurodegenerative disorders in the chronic phase. Growing evidence indicates that dysfunction of the glymphatic system, which is a cerebrospinal fluid-driven waste-clearance pathway, may contribute to this association. Glymphatic dysfunction after TBI can promote the accumulation of pathogenic proteins, including amyloid-β and hyperphosphorylated tau, thereby accepting progressive neurodegeneration. This review synthesizes current knowledge on the link between TBI-induced glymphatic dysfunction and subsequent neurodegeneration. Particular emphasis is placed on recent advances in magnetic resonance imaging (MRI) that enable in vivo evaluation of glymphatic function and related structural changes. Key MRI approaches include contrast-enhanced including, diffusion tensor imaging-derived analysis along the perivascular space (ALPS) index, and volumetric evaluation of the enlarged perivascular spaces and the choroid plexus. These MRI biomarkers enable noninvasive measurement of glymphatic dysfunction and their potential contribution to neurodegenerative processes. By integrating evidence from preclinical models and clinical studies, this review highlights the role of glymphatic dysfunction in the link between TBI and neurodegeneration. This underscores the utility of MRI-based markers for early detection, mechanistic insight, and the development of targeted interventions for TBI-associated neurodegenerative disorders.