Cerebral Venous Insufficiency as a Contributing Factor in Dementia: An Emerging Hypothesis

Emerging evidence suggests that disturbances in cerebral venous outflow may play a meaningful role in the development and progression of cognitive impairment. The brain's glymphatic system, which facilitates the clearance of metabolic waste, including β-amyloid and tau, relies on stable venous pressure gradients to drive perivascular and interstitial fluid movement. Venous insufficiency, whether from structural narrowing or functional outflow obstruction, can disrupt these gradients, reducing clearance efficiency and promoting protein accumulation, neuroinflammation, and white matter injury. Age-related changes in venous compliance, increased pulsatility, and stenosis of the dural venous sinuses have been observed in patients with mild cognitive impairment and dementia, raising the possibility that such hemodynamic alterations may be a significant part of neurodegenerative pathology. As venous sinus stenosis is a potentially treatable condition, it may represent a future therapeutic target. This review synthesizes current knowledge on the interplay between venous circulation and glymphatic function in brain health, outlines the mechanistic basis for venous contributions to cognitive decline, and highlights the need for systematic investigation of further therapeutic treatments in the context of age-related cognitive impairment.