International Psychogeriatrics
Volume 15, Supplement 1 - 2003
Vascular Factors in Alzheimer’s Disease RAJ N. KALARIA
ABSTRACT. Vascular involvement in Alzheimer disease (AD) is not necessarily coincident. Current
evidence suggests the neuropathology of Alzheimer type of dementia comprises more than amyloid
plaques and neurofibrillary tangles. At least a third of recognized AD cases may exhibit
cerebrovascular pathology, which also constitutes distinct small vessel disease. Cerebral
amyloid angiopathy, microvascular degeneration affecting the cerebral endothelium and smooth
muscle cells, basal lamina alterations, hyalinosis, and fibrosis are frequently evident in AD.
These changes may be accompanied by perivascular denervation that is causal in the cognitive
decline of AD. In addition, amyloid β protein appears directly involved in the degeneration of
both the larger perforating arterial vessels as well as cerebral capillaries, which represent
the blood-brain barrier. The cerebrovascular pathology in AD also encompasses macro- and
micro-infarctions, hemorrhages, lacunas, and ischemic white-matter changes. An interaction of
both perivascular mediators and derived factors would perturb the brain vasculature. Peripheral
vascular factors such as long-standing hypertension, atrial fibrillation, coronary or carotid
artery disease, and diabetes mellitus are also apparent in AD. These factors would modify the
cerebral circulation such that a sustained hypoperfusion or oligemia is impacted upon the aging
processes to induce the characteristic pathology.
