Venous dysfunction plays a critical role in "normal" white matter disease of aging

Area of Science:

• Neurology
• Radiology
• Gerontology

Background:

• Age-related cerebral white matter hyperintensities (WMHs) are common on MRI in older adults.
• WMHs are associated with cognitive decline, dementia, disability, and mortality.
• Current theories link WMHs to arteriosclerosis, but their distribution and inconsistent risk factor associations suggest alternative causes.

Purpose of the Study:

• To investigate the role of age-related hemodynamic cervical venous dysfunction in the development of WMHs.
• To propose an alternative hypothesis for the etiology of WMHs, focusing on venous pathology.

Main Methods:

• Review of existing literature on WMHs, aging, venous function, and blood-brain barrier (BBB) permeability.
• Analysis of the anatomical distribution of WMHs in relation to venous systems.
• Correlation of age-related changes in venous compliance, collagenosis, and BBB integrity with WMH development.

Main Results:

• WMH distribution often parallels the deep venous system, not typical arterial territories.
• Evidence suggests age-related hemodynamic venous dysfunction (reduced jugular vein compliance, reflux) and increased BBB permeability.
• Venous collagenosis increases with age, potentially contributing to venous dysfunction.

Conclusions:

• Age-related WMHs may be a consequence of venous dysfunction rather than solely arterial disease.
• Venous dysfunction could lead to increased venous pressure transmission to the brain.
• This increased pressure may subsequently disrupt the blood-brain barrier, resulting in WMHs.