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Hypertension and Alzheimer's disease: indirect effects through circle of Willis atherosclerosis.

ABSTRACT: Hypertension is common among older adults and is believed to increase susceptibility to Alzheimer's disease, but mechanisms underlying this relationship are unclear. Hypertension also promotes circle of Willis atherosclerosis, which contributes to cerebral hypoperfusion and arterial wall stiffening, two potential mechanisms linking hypertension to Alzheimer's disease. To examine the role of circle of Willis atherosclerosis in the association between hypertension and Alzheimer's disease neuropathology, we analysed post-mortem neuropathological data on 2198 decedents from the National Alzheimer's Coordinating Center database [mean (standard deviation) age at last visit 80.51 (1.95) and 47.1% female] using joint simultaneous (i.e. mediation) modelling. Within the overall sample and among Alzheimer's dementia decedents, hypertension was indirectly associated with increased neuritic plaques and neurofibrillary tangles through its association with circle of Willis atherosclerosis. Similar indirect effects were observed for continuous measures of systolic and diastolic blood pressure. These results suggest that hypertension may promote Alzheimer's disease pathology indirectly through intracranial atherosclerosis by limiting cerebral blood flow and/or dampening perivascular clearance. Circle of Willis atherosclerosis may be an important point of convergence between vascular risk factors, cerebrovascular changes and Alzheimer's disease neuropathology.

SUBMITTER: Eglit GML

PROVIDER: S-EPMC7846096 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Hypertension and Alzheimer's disease: indirect effects through circle of Willis atherosclerosis.

Eglit Graham M L GML Weigand Alexandra J AJ Nation Daniel A DA Bondi Mark W MW Bangen Katherine J KJ

Brain communications 20200721 2

Hypertension is common among older adults and is believed to increase susceptibility to Alzheimer's disease, but mechanisms underlying this relationship are unclear. Hypertension also promotes circle of Willis atherosclerosis, which contributes to cerebral hypoperfusion and arterial wall stiffening, two potential mechanisms linking hypertension to Alzheimer's disease. To examine the role of circle of Willis atherosclerosis in the association between hypertension and Alzheimer's disease neuropath ...[more]

PMID: 33543127

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Project description:BackgroundCircle of Willis is the main structure that provides constant and regular blood flow to the brain, protects the brain from ischemia. Stroke has remained the second leading cause of death globally in the last fifteen years. It is the fifth leading cause of death in the United States. It is also the leading cause of serious adult disability. Interlinked problems related to ischemic stroke are become increasing nowadays. Strong evidence is needed about the pooled measure of association between the circle of Willis (COW) and ischemic stroke. Therefore, this systematic review and meta-analysis were intended to provide compressive and up to date evidence on the association between the variations of COW and ischemic stroke using the available studies.MethodsPubMed, Google Scholar, Science Direct, and Cochrane Library databases were systematically searched. All essential data were extracted using a standardized data extraction template. The heterogeneity across studies was assessed by using the Cochrane Q test statistic, I2 test statistic, and P-values. A fixed-effect model was used to estimate the pooled effect of the measure association between COW and ischemic stroke.ResultsIn this meta-analysis, 2,718 participants were involved. The pooled measure of association between COW and ischemic stroke was 1.38 (95% CI 0.87, 2.19). Therefore, this indicated that the presence of any variation in COW was 1.38 times more likely to develop ischemic stroke as compared to the patent COW. The presence of hypoplasia/incompleteness in a posterior communicating artery (PcomA) [Pooled OR: 1.34 (95% CI 0.80, 2.25)] and anterior communicating artery (AcomA) [Pooled OR: 1.32 (95% CI 0.81, 2.19)] were a contributing factor for the development of ischemic stroke. Hypertension was the most common comorbid condition, followed by diabetes mellitus, smoking, coronary artery disease, and hyperlipidemia.ConclusionsThere was a non-significant positive association between COW variation and ischemic stroke in this meta-analysis.

Project description:BACKGROUND:It is not clear whether the configuration of the posterior part of the circle of Willis (CW) depends on the proximal part of the vertebrobasilar system. Our aim is to evaluate the posterior part of CW in association with different size of vertebral arteries (VA) in healthy volunteers. MATERIALS AND METHODS:The present study was based on a sample of 923 healthy volunteers who were examined from 2013 through 2018. The duplex ultrasonographic examination of the extracranial vertebral (VA) and carotid arteries was performed. VA was defined as hypoplastic (VAH) when VA diameter in the entire course was less than 2.5 mm. All the participants underwent magnetic resonance angiography (MRA) examination. All the component vessels of the circle of Willis were assessed in each individual. We classified the posterior communicating artery (PCoA) as presence PCoA, absence/hypoplastic PCoA and fetal-type posterior circle of Willis (FCW) in which the major stem of the posterior cerebral artery (PCA) arises from ipsilateral internal carotid artery (ICA). The comparison of the posterior part of CW was made in subjects with normal VA and VAH of a different degree (communicating with basilar artery (VAH-BA) and not communicating with the basilar artery (VAH-PICA)). RESULTS:FCW was found in 15.9% of subjects, bilaterally-in 2.3%. FCW was more frequent in individuals with VAH than in those with normal VA (accordingly, 28.8% vs. 13.5%, p<0.001. Moreover FCW was recorded in 50% of the subjects with VA-PICA in comparison with 13.5% of those with normal VA and 22.8% with VAH-BA, p<0.005. On the contrary, absence/hypoplasia of both PCoA was mostly found in the group with normal VA in comparison with VAH-BA and VAH-PICA (accordingly, 50.7%, 38.6% and 12.5%, p<0.01). CONCLUSION:Individuals with VAH have a different pattern of the posterior part of CW in comparison with those with normal VA. With the increasing degree of VAH, the proportion of FCW increases, while the proportion of absence/hypoplastic of both PCoA decreases.

Dataset Information

Hypertension and Alzheimer's disease: indirect effects through circle of Willis atherosclerosis.

Publications

Hypertension and Alzheimer's disease: indirect effects through circle of Willis atherosclerosis.

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