Optical measures of cerebral arterial function as predictors of brain and cognitive aging

脑血管健康（特别是动脉硬化或动脉硬化）是年龄相关疾病的重要因素。 在阿尔茨海默病（AD）和血管性痴呆等多种疾病中发挥着重要作用。 动脉炎是进行性的，被认为是不可逆的。因此，其早期发现至关重要。作为 心脏病研究和其他纵向研究广泛证明，生活方式因素， 特别是缺乏身体活动，在动脉硬化的发展中起着核心作用。脑动脉硬化是 目前，通过外周测量间接评估或更直接地在颈部和头部（颈动脉或经- 颅多普勒超声，TCD），其提供有用的临床信息，但仅在少数测量点。我们 实验室最近开发了一种新的成像方法，基于对用漫射光学测量的动脉脉搏的研究。 断层扫描（脉冲DOT），它允许整个皮质覆盖层的动脉状态的映射，具有高 可靠性和可复制性。我们已经表明，在正常老化的老年人中，PReFx（脉冲松弛）的低值 功能，指示动脉弹性的脉搏形状的测量）与年龄较大、较低的心肺功能相关。 健康（CRF），以及总体上更大的年龄相关性脑萎缩和白色信号异常（WMSA）。关键是，我们 还表明，从一个脑区到另一个脑区的动脉硬度的局部/区域变化与 同一地区的体积变化。这些区域效应提供了动脉健康之间更强的功能联系 和大脑老化的早期结构迹象，而不是来自动脉弹性的全球措施，指出 动脉功能在一系列事件中的重要性，随着时间的推移，这些事件可能导致认知和脑容量损失。在 拟议的研究，基于混合横截面/纵向（30个月）设计，涉及200人 在50 - 70岁之间，我们的目标是：（1）证明脉冲DOT与脑血管风险交叉相关， 在30个月的时间里，按亚临床风险存在程度分类的个体 与低CRF相关的因素预计也与动脉僵硬度的PReFx指数存在分级关系 与脑血管反应性（CVR）指数一样。然后，在随访期间降低PReFx脉冲-DOT值 预计会预测风险的恶化。(2)证明脑动脉的局部变化（超过30个月） 功能与脑结构的区域变化（即，指示脑萎缩和WMSA的体征）和 相同区域的血流参数（用磁共振成像，MRI测量）。(3)识别 基线和随访期间认知功能、局部血管硬化和CVR之间的关系。 我们预期血管硬化和血管反应性的区域性缺陷的一致性将与特定的 认知处理的缺陷这些研究结果不仅应提供信息，说明气候变化对全球的影响， 脑动脉硬度对大脑和认知老化轨迹的影响，以及对动脉硬度的区域分布的影响。在 从长远来看，这种方法可以为基础和临床应用中研究脑血管效应提供工具， 用于指导个体定制的早期干预措施，旨在预防与年龄相关的认知衰退，MCI和AD。

Cerebrovascular health (and in particular arterial stiffening, or arteriosclerosis) is a significant contributor to age-related decline, and exerts a central role in a number of pathologies, including Alzheimer's disease (AD) and vascular dementia. Arteriosclerosis is progressive and considered to be irreversible. Therefore its early detection is of critical importance. As extensively demonstrated by the Framingham Heart Study and other longitudinal research, life style factors, and in particular physical inactivity, play a central role in the development of arteriosclerosis. Cerebral arteriosclerosis is currently assessed either indirectly with peripheral measures or more directly in the neck and head (with carotid or trans- cranial Doppler sonography, TCD), which provide useful clinical information but at just a few measurement points. Our lab has recently developed a new imaging approach, based on the study of the arterial pulse measured with diffuse optical tomography (pulse-DOT), which allows for the mapping of arterial status across the entire cortical mantle, with high reliability and replicability. We have shown that in normally aging older adults, low values of PReFx (pulse relaxation function, a measure of pulse shape indicative of arterial elasticity) are correlated with older age, lower cardiorespiratory fitness (CRF), and overall greater age-related brain atrophy and white matter signal abnormalities (WMSA). Crucially, we have also shown that local/regional variations in arterial stiffness from one brain region to another correlate with volumetric variations in the same regions. These regional effects provide a stronger functional link between arterial health and early structural signs of brain aging than those derived from global measures of arterial elasticity, pointing at the importance of arterial function in the chain of events that may lead, over time, to cognitive and brain volumetric losses. In the proposed research, based on a mixed cross-sectional/longitudinal (30 month) design involving 200 individuals between 50 and 70 years of age, we aim to: (1) Demonstrate that pulse-DOT will relate to cerebrovascular risk cross- sectionally and also prospectively over a 30-month period. Individuals classified by degree of presence of sub-clinical risk factors relating to low CRF are expected to show a graded relationship with the PReFx index of arterial stiffness, as well as with indices of cerebrovascular reactivity (CVR). Decreasing PReFx pulse-DOT values over follow-up are then expected to predict a worsening of risk. (2) Demonstrate that regional changes (over 30 months) in cerebral arterial function are associated with regional changes in brain structural (i.e., indicating signs of brain atrophy and WMSA) and blood flow parameters in the same regions (measured with magnetic resonance imaging, MRI). (3) Identify the relationship between cognitive function, regional vascular stiffening and CVR at baseline and over the follow-up period. We anticipate a concordance of regional deficits in vascular stiffening and vascular reactivity that will relate to specific deficits in cognitive processing. These findings should provide information not only on global effects of variations in cerebral arterial stiffness on brain and cognitive aging trajectories, but also on the regional profiles of arterial stiffness. In the long term this approach may provide a tool for studying cerebrovascular effects in basic and clinical applications, and for guiding individually tailored early interventions, designed to prevent age-related cognitive decline, MCI and AD.