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 in order to identify novel therapeutic targets. Age-related changes to 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 while 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 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.

中文翻译：

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大动脉僵硬和大脑健康：来自动物模型的见解

没有有效的治疗方法可以阻止或逆转与年龄相关的认知能力下降和阿尔茨海默病的进展。因此，迫切需要了解疾病病因和进展的潜在机制，以确定新的治疗靶点。与年龄相关的脉管系统变化，特别是大弹性动脉僵硬的增加，现在被认为是大脑衰老的重要因素。越来越多的证据表明，健康老年人和阿尔茨海默病患者的大动脉僵硬与认知障碍之间存在关联。然而，对人类的研究仅限于相关证据，而动物模型允许研究人员探索将动脉僵硬与神经认知功能障碍和疾病联系起来的致病机制。最近，已经报道了几种直接调节大动脉硬度的啮齿动物模型及其对大脑的影响。这些模型中的共同结果已经出现，包括证据表明更大的大动脉僵硬会导致与氧化应激和炎症信号传导增加相关的脑血管功能障碍。这篇小型综述的目的是强调最近的发现，将大动脉僵硬与有害的大脑结果联系起来，特别关注从动物模型中获得的致病证据。