With advancing age, the periventricular and subcortical white matter becomes susceptible to a heterogeneous assortment of tissue alterations that cannot be easily categorized in terms of traditionally defined neuropathologic disease. These alterations, which appear radiolucent on CT and hyperintense on T2-weighted MR imaging, are more common in patients with chronic hypertension and perhaps other microvascular arteriosclerotic risk factors. Examination of the affected tissue reveals a spectrum of histologic change that is graded with respect to pathologic severity. The majority of the alterations are of low histopathologic grade and exert minimal clinical effects. Frequently observed microscopic changes include dilated perivascular (Virchow-Robin) spaces, mild demyelination, gliosis, and diffuse regions neuropil vacuolation. Associated clinical abnormalities, when present, are usually confined to deficits of attention, mental processing speed, and psychomotor control. These deficits may often be demonstrable only through neuropsychologic testing. There is some evidence that the cognitive symptoms of AD may be exacerbated by the concomitant presence of these white matter alterations, but an etiologic link between AD and radiographically detectible white matter changes remains speculative. Occasionally, histologically severe white matter lesions may occur that result in dementia and focal neurologic impairment. These lesions are characterized by extensive arteriosclerosis, diffuse white matter necrosis, and lacunar infarction; affected patients may receive a diagnosis of Binswanger's disease or subcortical arteriosclerotic encephalopathy. Nevertheless, severe ischemic white matter pathology of this type is uncommon as an explanation for serious neurologic dysfunction, and clinicians must carefully weigh other categories of neuropathology before making a diagnosis of Binswanger's disease. Alternative diagnostic considerations include neurodegenerative illnesses such as AD, cerebral infarction, neoplasm, and other forms of white matter pathology such as those due to infection, inflammation, a primary demyelinative condition, or metabolic leukodystrophy.