Role of Age-Related Alterations of the Cerebral Venous Circulation in the Pathogenesis of Vascular Cognitive Impairment

Am J Physiol Heart Circ Physiol. 2019 May 1;316(5):H1124-H1140. doi: 10.1152/ajpheart.00776.2018. Epub 2019 Mar 8.


There has been an increasing appreciation of the role of vascular contributions to cognitive impairment and dementia (VCID) associated with old age. Strong preclinical and translational evidence links age-related dysfunction and structural alterations of the cerebral arteries, arterioles, and capillaries to the pathogenesis of many types of dementia in the elderly, including Alzheimer's disease. The low-pressure, low-velocity, and large-volume venous circulation of the brain also plays critical roles in the maintenance of homeostasis in the central nervous system. Despite its physiological importance, the role of age-related alterations of the brain venous circulation in the pathogenesis of vascular cognitive impairment and dementia is much less understood. This overview discusses the role of cerebral veins in the pathogenesis of VCID. Pathophysiological consequences of age-related dysregulation of the cerebral venous circulation are explored, including blood-brain barrier disruption, neuroinflammation, exacerbation of neurodegeneration, development of cerebral microhemorrhages of venous origin, altered production of cerebrospinal fluid, impaired function of the glymphatics system, dysregulation of cerebral blood flow, and ischemic neuronal dysfunction and damage. Understanding the age-related functional and phenotypic alterations of the cerebral venous circulation is critical for developing new preventive, diagnostic, and therapeutic approaches to preserve brain health in older individuals.

Keywords: cerebral circulation; senescence; vascular cognitive impairment; vascular contributions to cognitive impairment and dementia; vein.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Age Factors
  • Animals
  • Cerebral Veins / physiopathology*
  • Cerebrovascular Circulation*
  • Cognition*
  • Cognitive Aging / psychology*
  • Cognitive Dysfunction / cerebrospinal fluid
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / physiopathology*
  • Cognitive Dysfunction / psychology
  • Dementia, Vascular / cerebrospinal fluid
  • Dementia, Vascular / etiology
  • Dementia, Vascular / physiopathology*
  • Dementia, Vascular / psychology
  • Humans
  • Risk Factors