Key result
Animal models demonstrate that greater large artery stiffness causes cerebrovascular dysfunction, increased oxidative stress, neuroinflammation, and cognitive impairment.
Why the study?
Human studies linking large artery stiffness to cognitive decline provide only correlative evidence, creating a need to explore causative mechanisms in animal models to identify novel therapeutic targets.
Does large artery stiffness cause cerebrovascular dysfunction and neurocognitive impairment in animal models?
Does large artery stiffness cause cerebrovascular dysfunction and neurocognitive impairment in animal models?
Animal models provide causative evidence that large artery stiffness leads to cerebrovascular dysfunction, oxidative stress, and inflammatory signaling, contributing to cognitive decline.
Cautions against clinical extrapolation from animal data; leaves open whether stiffness drives human cerebrovascular and cognitive outcomes.
There are no effective treatments available to halt or reverse the progression of age-related cognitive decline and Alzheimer's disease. Thus, there is an urgent need to understand the underlying mechanisms of disease etiology and progression to identify novel therapeutic targets. Age-related changes to the vasculature, particularly increases in stiffness of the large elastic arteries, are now recognized as important contributors to brain aging. There is a growing body of evidence for an association between greater large artery stiffness and cognitive impairment among both healthy older adults and patients with Alzheimer's disease. However, studies in humans are limited to only correlative evidence, whereas animal models allow researchers to explore the causative mechanisms linking arterial stiffness to neurocognitive dysfunction and disease. Recently, several rodent models of direct modulation of large artery stiffness and the consequent effects on the brain have been reported. Common outcomes among these models have emerged, including evidence that greater large artery stiffness causes cerebrovascular dysfunction associated with increased oxidative stress and inflammatory signaling. The purpose of this mini-review is to highlight the recent findings associating large artery stiffness with deleterious brain outcomes, with a specific focus on causative evidence obtained from animal models. We will also discuss the gaps in knowledge that remain in our understanding of how large artery stiffness affects brain function and disease outcomes.
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Winder et al. (2020) conducted a review in Large artery stiffness and cognitive decline. Animal models demonstrate that greater large artery stiffness causes cerebrovascular dysfunction, increased oxidative stress, neuroinflammation, and cognitive impairment.
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