The neuropathology of vascular dementia

Ischemic infarction is the main lesion underlying vascular dementia (VaD) but cases also occur after brain hemorrhage, as well as with hypoperfusive brain ischemia. Ischemic strokes include large-vessel cortico-subcortical strokes and lacunes resulting from small-vessel disease. Arteriolosclerosis and fibrinoid necrosis are the most common forms of small-vessel disease in the elderly. Although it was originally proposed that vascular dementia could result from repeated strokes with loss of >100 mL of brain tissue loss (multi-infarct dementia), it is currently held that the location of the stroke is probably more relevant to cognitive loss and dementia. In fact, a single, strategically located stroke may interrupt cortico-subcortical circuits important for memory and cognition. Hypoperfusive lesions include border-zone cortico-subcortical infarcts, temporal lobe sclerosis, and periventricular incomplete ischemic leukoencephalopathy. The latter two lesions are commonly seen in the elderly as a result of narrowing and tortuosity of medullary arterioles irrigating these distal territories, plus cardiac pump failure. Binswanger disease is characterized by extensive periventricular ischemic leukoencephalopathy that spares the arcuate U-fibers, and presence of lacunar strokes. CADASIL is a genetic form of vascular dementia characterized by a cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. CADASIL is due to a mutation of the Notch3 gene in chromosome 19. Intracerebral hemorrhages in strategic locations may produce vascular dementia. Lesions in the basal forebrain that damage cholinergic nuclei, such as those resulting from a ruptured aneurysm of the anterior communicating artery, may produce vascular dementia. Some patients with subarachnoid hemorrhage develop normal-pressure hydrocephalus. Cerebral amyloid angiopathy (congophilic angiopathy) may cause lobar hemorrhages and dementia. Vascular lesions, in particular, microinfarcts, are frequently found in patients with a clinical diagnosis of Alzheimer disease. These mixed forms of dementia are likely to become the most common form of dementia in the elderly.