Intracranial atherosclerosis as a contributing factor to Alzheimer's disease dementia

Abstract

Background A substantial body of evidence amassed from epidemiologic, correlative and experimental studies strongly associates atherosclerotic vascular disease (AVD) with Alzheimer's disease (AD). Depending on the precise interrelationship between AVD and AD, systematic application of interventions to maintain vascular health and function as a component of standard AD therapy offers the prospect of mitigating what is presently the inexorable course of dementia. To assess this hypothesis it is vital to rigorously establish the measures of AVD that are most strongly associated with an AD diagnosis. Methods A precise neuropathological diagnosis was established for all subjects using a battery of genetic, clinical, and histological methods. The severity of atherosclerosis in the circle of Willis (CW) was quantified by direct digitized measurement of arterial occlusion in postmortem specimens and compared between AD and non-demented control (NDC) groups by calculating a corresponding index of occlusion. Results Atherosclerotic occlusion of the CW arteries was more extensive in the AD group than the NDC group. Statistically significant differences were also observed between control and AD groups with regard to Braak stage, total plaque score, total NFT score, total white matter rarefaction score, brain weight, MMSE scores and apolipoprotein E allelic frequencies. Conclusions Our results, combined with a consideration of the multifaceted impacts of impaired cerebral circulation, suggest an immediate need for prospective clinical trials to assess the efficacy of AD prevention using anti-atherosclerotic agents.

The total alkaloids from <em>Coptis chinensis</em> Franch improve cognitive deficits in type 2 diabetic rats

“…Furthermore, an epidemiological study has reported an association between Alzheimer’s disease and some vascular risk factors, including hyperlipidemia 19. Therefore, hyperlipidemia-induced intracranial vascular dysfunction may be a contributing factor to cognitive deficits 20. Our results indicated that TAC also attenuated the increased levels of NEFA, TC, TG, and ApoB in type 2 diabetic rats.…”

Vascular dysfunction in the pathogenesis of Alzheimer's disease — A review of endothelium-mediated mechanisms and ensuing vicious circles

“…Substantial evidence from in vitro and biopsy studies also supports the hypothesis that chronic cerebral hypoperfusion plays an important role in the development of AD [7,72,75,[157][158][159]. Hypoperfusion-induced hypoxia evokes vascular responses, in which endothelial cells in the cerebral microcirculation play a central role.…”

Does vascular pathology contribute to Alzheimer changes?

“…Few longitudinal studies followed to autopsy support the thesis that hypoxia or oligaemia increases accumulation of AD pathological changes and cognitive dysfunction. Roher and colleagues [55][56][57] have shown that atherosclerotic occlusion of the circle of Willis arteries was more extensive in the AD subjects accompanied by a greater burden of neurofibrillary pathology and white matter rarefaction than in the non-demented ageing individuals but not against subjects with VaD. These observations were not necessarily influenced by the presence of an APOE ε4 allele, however.…”