Observations on cerebral amyloid angiopathy and microvascular pathology in Alzheimer's disease and vascular dementia

Abstract: Dementia is a state of permanent loss of cognitive function, most commonly affecting the elderly. With a rapidly growing aged population, the spectrum of disorders that lead to dementia is exerting an ever-increasing toll on patients, families and society alike. The most common dementing disorders are Alzheimer's disease and vascular dementia. Although Alzheimer's disease is very common and was described almost a century ago, the pathomechanisms are imperfectly understood, and mainly symptomatic therapy is available. Treatment options are even more meagre in vascular dementia, but in many cases, this disorder can possibly be prevented by risk factor management.

Since both Alzheimer's disease and vascular dementia are common in the elderly population, it is not uncommon for both diseases to be present to some degree in the same patient. Increasing evidence suggests that the disease mechanisms not only coexist, but that they interact synergistically, further exacerbating the clinical disorder. The purpose of this thesis was to explore features of vascular pathology in Alzheimer's disease and vascular dementia, to improve basic understanding of the disease processes in play.

We have shown that one of the major hallmarks of Alzheimer's disease, deposition of amyloid protein in the cerebrovasculature (cerebral amyloid angiopathy), is surprisingly common in vascular dementia, and frequently more severe than in Alzheimer's disease. In Alzheimer's disease, cerebral amyloid angiopathy is associated with ischemic white matter disease, but in vascular dementia, cerebral amyloid angiopathy is associated with cortical microinfarctions. Furthermore, the interrelationship between the amyloid beta (A-beta) peptide species deposited is affected by the presence of cerebrovascular disease, which is associated with a relative increase in deposition of the more fibrillogenic and toxic variant of the Ab peptide, and more severe degeneration of vascular components.