The beat that clears the brain: Cardiac pulsatility as a driver of glymphatic flow during sleep

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The brain, long considered an organ with limited means of waste disposal, is now understood to possess a highly efficient clearance network: the glymphatic system. This perivascular network facilitates the exchange of cerebrospinal fluid with interstitial fluid, clearing metabolic byproducts, including neurotoxic proteins such as amyloid-β and tau. The system’s activity is not constant; it is overwhelmingly active during sleep, particularly the deep, slow-wave stages. A critical and often underappreciated driver of this process is the relentless, rhythmic pulsatility of cerebral arteries, powered by the cardiac cycle. This integrative review aims to synthesize evidence to build a wide-ranging picture of the heart–sleep–brain axis. We explored how the mechanical energy of the heartbeat is harnessed to propel cerebrospinal fluid through the brain’s parenchyma and how this process is exquisitely modulated by sleep-dependent changes in autonomic tone and interstitial space. Furthermore, we detailed how common cardiovascular pathologies, including atrial fibrillation, heart failure, hypertension, and arterial stiffness, mechanistically disrupt this clearance pathway. Such disruptions provide a compelling, non-vascular explanation for the strong epidemiological link between heart disease and neurodegenerative disorders such as Alzheimer’s disease. Finally, we discussed the diagnostic and therapeutic implications of this axis, from novel neuroimaging techniques to assess glymphatic function to the potential for cardiovascular and sleep-based interventions to preserve long-term brain health. This neurocardiology framework reframes the heart’s role from a simple supplier of blood to an active custodian of the sleeping brain’s integrity.