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

脑血管健康(尤其是动脉硬化或动脉硬化)是与年龄相关的一个重要因素 在许多病理过程中发挥核心作用，包括阿尔茨海默病(AD)和血管性痴呆。 动脉硬化是进行性的，被认为是不可逆转的。因此，它的早期发现至关重要。AS 弗雷明翰心脏研究和其他纵向研究、生活方式因素和 尤其是缺乏体力活动，在动脉硬化的发展中起着核心作用。脑动脉硬化症 目前通过外周测量间接评估，或更直接地在颈部和头部进行评估(使用颈动脉或经 头颅多普勒超声(TCD)，提供有用的临床信息，但仅在几个测量点。我们的 实验室最近开发了一种新的成像方法，基于对漫反射光学测量的动脉脉搏的研究 断层扫描(Pulse-DOT)，它允许绘制整个皮质地幔上的动脉状态图，具有高 可靠性和可复制性。我们已经证明，在正常衰老的老年人中，PReFx(脉搏松弛)的低值 功能)与年龄较大、心肺功能较低的人有关 健康(CRF)，以及总体上更严重的年龄相关性脑萎缩和白质信号异常(WMSA)。至关重要的是，我们 还表明，动脉硬度从一个大脑区域到另一个大脑区域的局部/区域差异与 相同区域的体积变化。这些区域性效应在动脉健康之间提供了更强的功能联系 以及大脑老化的早期结构迹象，而不是来自全球动脉弹性测量的迹象，指出 动脉功能在一系列事件中的重要性，随着时间的推移，这些事件可能会导致认知和大脑体积的丧失。在……里面 这项拟议的研究基于一项横截面/纵向(30个月)混合设计，涉及200名个体 在50到70岁之间，我们的目标是：(1)证明脉搏-DOT将与脑血管风险交叉相关。 在30个月的时间内分阶段和前瞻性地进行。按亚临床风险存在程度分类的个人 与低CRF相关的因素预计也与动脉僵硬的PReFx指数显示出分级关系 脑血管反应性指标(CVR)。然后，在随访期间降低PReFx脉冲点数 预计将预测风险的恶化。(2)脑动脉局部改变(30个月以上) 功能与大脑结构的区域性变化有关(即，表明大脑萎缩和WMSA的迹象)和 相同区域的血流参数(用磁共振成像测量)。(3)确定 基线及随访期认知功能、局部血管硬化与CVR的关系。 我们预计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。这些发现应该不仅提供关于全球气候变化影响的信息 脑动脉僵硬对大脑和认知衰老轨迹的影响，也是对动脉僵硬区域轮廓的影响。在……里面 从长远来看，这种方法可能为在基础和临床应用中研究脑血管效应提供一种工具，并且 用于指导个别量身定做的早期干预措施，旨在防止与年龄相关的认知下降、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.