The glymphatic system plays a crucial role in clearing metabolic waste from the brain, and impaired flow through this system has been linked to neurodegenerative conditions, including Alzheimer’s disease. Research shows that reduced glymphatic activity correlates with the severity of Alzheimer’s disease, indicating its potential as a target for prevention or treatment. Recent studies using diffusion MRI have provided insights into the association between glymphatic dysfunction and Alzheimer’s disease progression, highlighting the importance of addressing fluid clearance mechanisms in combating the disease. This study explores the longitudinal relationship between glymphatic activity, markers of Alzheimer’s pathology, and cognitive decline, suggesting that glymphatic failure may precede amyloid deposition and serve as a predictor of disease progression. Link: https://doi.org/10.1002/alz.13789.