Abstract
Sleep disruption is nearly universal during critical illness and is increasingly linked to long-term cognitive impairment among intensive care unit survivors. Advances in neuroscience have highlighted the glymphatic system - a brain-wide perivascular network that clears metabolic waste such as β-amyloid and phosphorylated tau - as a plausible mechanism connecting sleep disturbance to adverse neurocognitive outcomes. Glymphatic transport is highly state-dependent, functioning optimally during slow-wave sleep and diminishing with wakefulness or fragmented sleep. This invited review synthesizes preclinical and human evidence showing that sleep fragmentation and loss of slow-wave sleep impair cerebrospinal fluid-interstitial fluid exchange, promote accumulation and spread of tau and other neurotoxic proteins, and may accelerate neurodegenerative trajectories. We discuss how commonly used sedatives may induce unconsciousness without reproducing the coordinated neuromodulatory and neurovascular conditions of natural slow-wave sleep, creating "pseudo-sleep" that may fail to support metabolic clearance. We propose glymphatic dysfunction as an integrative pathway linking intensive care unit sleep disruption, inflammation, and sedative exposure to persistent deficits in memory, attention, and executive function after critical illness.