Pathophysiologic Mechanisms in the Development of Age-Related White Matter Changes of the Brain

Magnetic resonance imaging (MRI) has dramatically enhanced our capability of detecting age-related changes of the brain even before they become clinically apparent. Among those are preferentially alterations of the white matter in periventricular, deep and subcortical locations which display high signal intensity on both proton density- and T2-weighted images. Correlative histopathologic findings show hyperintense periventricular capping of the frontal horns to reflect predominantly a specific anatomic situation characterized by loosely arranged fine-fiber tracts with low myelin and high extracellular fluid content. A smooth halo of periventricular hyperintensity has been linked to disruption of the ependymal lining with subependymal gliosis and concomitant loss of myelin. In contrast, punctate, early confluent and confluent hyperintensities in the deep and subcortical white matter as well as irregular periventricular hyperintensity appear to be of vascular origin. Punctate lesions tend to correspond to a perivascular reduction in myelin content with atrophy of the neuropil and seem to constitute a negligible extent of tissue damage from low permeability through thickened arteriolar walls. Early confluent and confluent hyperintensities, however, indicate more extensive ischemic damage consistent with advanced microangiopathy.