The role of cerebral ischemia in Alzheimer's disease

The Alzheimer type of dementia and stroke are known to increase at comparab le rates with age. Recent advances suggest that vascular risk factors linke d to cerebrovascular disease and stroke in the elderly significantly increa se the risk of developing Alzheimer's disease (AD). These include atheroscl erosis, atrial fibrillation, coronary artery disease, hypertension, and dia betes mellitus. Moreover, review of various autopsy series shows that 60-90 % of AD cases exhibit variable cerebrovascular pathology. Although some vas cular lesions such as cerebral amyloid angiopathy, endothelial degeneration , and periventricular white matter lesions are evident in most cases of AD, a third will exhibit cerebral infarction. Despite the interpretation of pa thological evidence, longitudinal clinical studies suggest that the co-exis tence of stroke and AD occurs more than by chance alone. Strokes known to o ccur in patients with Alzheimer syndrome and most frequently in the oldest old substantially worsen cognitive decline and outcome, implicating some in teraction between the disorders. Nevertheless, the nature of a true relatio nship between the two disorders seems little explored. What predisposes to strokes in underlying cognitive decline or AD? Is it possible that cerebral ischemia is a causal factor for AD? I examined several vascular factors an d the vascular pathophysiology implicated in stroke and AD, and propose tha t cerebral ischemia or oligemia may promote Alzheimer type of changes in th e aging brain. Irrespective of the ultimate pathogenetic mechanism, these a pproaches implicate that management of peripheral vascular disease is impor tant in the treatment or prevention of Alzheimer's disease or mixed dementi a. (C) 2000 Elsevier Science Inc. All rights reserved.