title: Living beyond our physiological means: small vessel disease of the brain is an expression of a systemic failure in arteriolar function: a unifying hypothesis.
abstract: OBJECTIVE
  It is our premise that the pathophysiology of small vessel disease in the brain is similar to small vessel disease in other heavily perfused tissues and that the presence of small vessel disease elsewhere in the body foretells its presence in the brain as well as its consequences on cognitive function. The hypothesis presented in this article is that small vessel disease is a systemic condition of aging that is exacerbated by vascular risk factors, which results from dysfunction of arteriolar perfusion. This condition, which we term systemic arteriolar dysfunction, affects the brain as well as a number of extracranial systems.
  
  
  RESULTS
  Recent literature is synthesized to suggest a possible etiology of this condition, highlighting the multiple pathways that may conspire to produce the endothelial and other vascular changes seen in systemic arteriolar dysfunction.
  
  
  CONCLUSIONS
  Regardless of the etiology, we emphasize that small vessel disease is a systemic condition with major healthcare consequences, requiring a new paradigm in the way we practice medicine. Because this condition can be decelerated by control of vascular risk factors, doing so may significantly reduce morbidity, mortality, and healthcare costs.
authors.affiliation: Division of Neurology, University of Ottawa, Neuroscience Research, The Ottawa Health Research Institute, the Canadian Stroke Network, and The Heart & Stroke Foundation Centre for Stroke Recovery, Ottawa, Ontario, Canada.
authors.forename: Charlie S
authors.initials: CS
authors.lastname: Thompson
authors.forename: Antoine M
authors.initials: AM
authors.lastname: Hakim
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001160:Arterioles / Q000473:pathology*; D002561:Cerebrovascular Disorders / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology; D008279:Magnetic Resonance Imaging; D012164:Retinal Diseases / Q000209:etiology / Q000473:pathology; D012307:Risk Factors; D014652:Vascular Diseases / Q000378:metabolism / Q000473:pathology*