Review: Vascular dementia: clinicopathologic and genetic considerations.

The incidence and severity of cerebrovascular disease (CVD) increase with advancing age, as does the risk of developing Alzheimer's disease (AD). Not surprisingly, heterogeneous forms of CVD may coexist with AD changes in the 'ageing brain'. These include angiopathies (affecting both large and small arteries) that result from 'classical' risk factors (hypertension, smoking and diabetes) and others (cerebral amyloid angiopathy) that are biochemically closely linked to AD. The morphologic consequences of these various vascular diseases are infarcts and/or haemorrhages of varying sizes within the brain, which lead to neurocognitive decline that may mimic AD - though the vascular abnormalities are usually detectable by neuroimaging. More subtle effects of CVD may include neuroinflammation and biochemical 'lesions' that have no reliable morphologic correlate and thus escape the attention of even an experienced Neuropathologist. The pathogenesis of hippocampal injury resembling ischaemic change - commonly seen in the brains of geriatric subjects - remains controversial. In recent years, genetically determined forms of microangiopathy (e.g. CADASIL, CARASIL, Trex1-related microangiopathies, CARASAL, familial forms of cerebral amyloid angiopathy or CAA) have provided interesting cellular and molecular clues to the pathogenesis of sporadic microvascular disease such as arteriolosclerosis and AD-related CAA.