Potential Mechanism of Venous System for Leukoaraiosis: From post-mortem to in vivo Research

<b><i>Background:</i></b> Leukoaraiosis (LA), widely accepted as a feature of cerebral small vessel disease, significantly increases the incidence of stroke, dementia, and death. Cerebral small artery disease has been considered as one of the main causes of LA. However, since the term “venous collagenosis” (VC) was proposed in an atrophy research in 1995, there have been pathological and neuroimaging studies proving the association between the venous system and LA in aging, Alz­heimer’s disease (AD), and Parkinson’s disease. <b><i>Summary:</i></b> Autopsy studies confirmed that thickening of the lumen wall in venules, which results from the deposition of collagen I and III, leading to vessel stenosis or occlusion, is closely associated with LA. Susceptibility-weighted imaging research revealed a controversial association of deep medullary veins and LA in vivo, regarding which there are no standard criteria currently. Nevertheless, retinal venous changes had been reported to increase the risk of LA development, providing a novel way for in vivo evaluation. As for the internal jugular vein, jugular venous reflux could double the LA score in aging and modulate circulation of cerebral spinal fluids. <b><i>Key Messages:</i></b> Disruption of the venous system was notably associated with LA in aging, AD, and Parkinson’s disease post-mortem and in in vivo models. The venous pathological changes may induce cerebral hypoperfusion, drainage system disruption, and vasogenic oedema in the veins around the periventricular white matter. The clarification of VC in LA may provide an early prevention and early treatment strategy for LA patients.