Pathophysiology of age-related cerebral white matter changes

Cerebrovascular Diseases
Leonardo Pantoni

Abstract

The pathogenesis of age-related cerebral white matter changes (WMC) is still a matter of investigation. Alterations of deep small vessels, such as arteriolosclerosis, are considered to play a central role in the development of WMC. Stenosis or occlusion of small vessels may cause sudden or more chronic ischemia resulting in small areas of necrosis (lacunar infarction) or diffuse alterations consistent with the definition of white matter incomplete infarct. Moreover, the arteriolosclerotic changes may cause loss of autoregulation in the deep white matter and consequent cerebral blood flow fluctuations in response to changes of systemic blood pressure. Both these types of mechanisms may be particularly harmful because the blood supply of the white matter is of the terminal type with scarce anastomoses. Other pathophysiological hypotheses on the origin of WMC have been raised, and they can probably be considered as complementary to the ischemic one. The small vessel alterations could lead to damage of the blood-brain barrier and chronic leakage of fluid and macromolecules in the white matter. The increased interstitial fluid concentration in abnormal white matter may be also a consequence of arterial hypertensive bouts. Geneticall...Continue Reading

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