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

脑动脉功能的光学测量作为大脑和认知衰老的预测因子

• 批准号: 10394936
• 负责人: Monica Fabiani
• 金额: $ 69.2万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10394936
• 关键词: 5 year old; Age; Age-Years; Age-associated memory impairment; Alzheimer' s Disease; Aorta; Arteriogram; Arteriosclerosis; Blood Vessels; Blood flow; Body mass index; Brain; Brain region; Cerebral Arteriosclerosis; Cerebral small vessel disease; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrum; Chronic stress; Clinical; Cognitive; Cognitive aging; Data; Dementia; Development; Diastolic blood pressure; Early Diagnosis; Early Intervention; Elasticity; Elderly; Event; Evolution; Female; Framingham Heart Study; Head and neck structure; Health; Hypertension; Image; Impaired cognition; Individual; Intervention; Investigation; Lead; Link; Location; Magnetic Resonance Imaging; Maps; Measurement; Measures; Methods; Modeling; Neurologic; Optics; Outcome; Pathology; Pattern; Peripheral; Physiologic pulse; Play; Prediabetes syndrome; Prevention; Relaxation; Research; Resolution; Risk; Risk Factors; Role; Sampling; Shapes; Signal Transduction; Smoking; Stenosis; Surface; System; Time; Transcranial Doppler Ultrasonography; Ultrasonography; Variant; Vascular Dementia; age related; aging brain; arm; arterial stiffness; base; blood lipid; cardiorespiratory fitness; cerebral atrophy; cerebrovascular; cerebrovascular health; clinical application; cognitive function; design; diffuse optical tomography; economic cost; femoral artery; follow-up; high body mass index; imaging approach; indexing; innovation; lifestyle factors; male; middle age; mild cognitive impairment; normal aging; novel; physical inactivity; prevent; prospective; societal costs; therapy design; tool; white matter; 5 year old; Age; Age-Years; Age-associated memory impairment; Alzheimer' s Disease; Aorta; Arteriogram; Arteriosclerosis; Blood Vessels; Blood flow; Body mass index; Brain; Brain region; Cerebral Arteriosclerosis; Cerebral small vessel disease; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrum; Chronic stress; Clinical; Cognitive; Cognitive aging; Data; Dementia; Development; Diastolic blood pressure; Early Diagnosis; Early Intervention; Elasticity; Elderly; Event; Evolution; Female; Framingham Heart Study; Head and neck structure; Health; Hypertension; Image; Impaired cognition; Individual; Intervention; Investigation; Lead; Link; Location; Magnetic Resonance Imaging; Maps; Measurement; Measures; Methods; Modeling; Neurologic; Optics; Outcome; Pathology; Pattern; Peripheral; Physiologic pulse; Play; Prediabetes syndrome; Prevention; Relaxation; Research; Resolution; Risk; Risk Factors; Role; Sampling; Shapes; Signal Transduction; Smoking; Stenosis; Surface; System; Time; Transcranial Doppler Ultrasonography; Ultrasonography; Variant; Vascular Dementia; age related; aging brain; arm; arterial stiffness; base; blood lipid; cardiorespiratory fitness; cerebral atrophy; cerebrovascular; cerebrovascular health; clinical application; cognitive function; design; diffuse optical tomography; economic cost; femoral artery; follow-up; high body mass index; imaging approach; indexing; innovation; lifestyle factors; male; middle age; mild cognitive impairment; normal aging; novel; physical inactivity; prevent; prospective; societal costs; therapy design; tool; white matter

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.

脑血管健康（尤其是动脉僵硬或动脉硬化）是与年龄相关的重要原因 衰落，并在许多病理中发挥着核心作用，包括阿尔茨海默氏病（AD）和血管性痴呆。 动脉硬化是进行性的，被认为是不可逆的。因此，其早期发现至关重要。作为 弗雷明汉心脏研究和其他纵向研究，生活方式因素以及在 特殊的身体不活跃，在动脉硬化发展中起着核心作用。大脑动脉硬化是 目前通过外周措施间接评估或直接在颈部和头部进行评估（用颈动脉或trans- 颅底多普勒超声检查，TCD），可提供有用的临床信息，但仅在几个测量点。我们的 实验室最近基于对弥散光学测量的动脉脉冲的研究开发了一种新的成像方法 断层扫描（脉冲点），允许在整个皮质地幔中映射动脉状态，高 可靠性和可复制性。我们已经表明，在正常老年老年人中，Prefx值低（脉冲松弛 功能，指示动脉弹性的脉冲形状的度量）与年龄较大，心肺 健身（CRF）以及与年龄相关的脑萎缩和白质信号异常（WMSA）的总体总体。至关重要的是，我们 还表明，从一个大脑区域到另一个大脑区域的动脉刚度的局部/区域变化与 同一区域的体积变化。这些区域效应在动脉健康之间提供了更强的功能联系 大脑衰老的早期结构迹象比从全球动脉弹性测量中得出的结构迹象，指向 动脉功能在可能导致认知和大脑体积损失的事件链中的重要性。在 拟议的研究基于混合的横截面/纵向（30个月）设计，涉及200个人 在50至70岁之间，我们的目的是：（1）证明脉冲点与脑血管风险跨 - 在一个30个月的时间内进行分段和前瞻性。按照次临床风险的程度分类的个人 与低CRF有关的因素也有望显示与动脉僵硬的PERFX指数的分级关系 与脑血管反应性指数（CVR）一样。然后，随访时降低PERFX脉冲点值 有望预测风险恶化。 （2）证明脑动脉的区域变化（超过30个月） 功能与大脑结构的区域变化有关（即指示脑萎缩和WMSA的迹象）和 同一区域中的血流参数（用磁共振成像测量，MRI）。 （3）确定 在基线和随访期间，认知功能，区域血管僵硬和CVR之间的关系。 我们预计血管僵硬和血管反应性的区域缺陷将与特定有关 认知处理的缺陷。这些发现不仅应提供有关全球变化影响的信息 大脑和认知衰老轨迹的大脑动脉僵硬，以及动脉僵硬的区域谱。在 长期的这种方法可以为研究基本和临床应用中研究脑血管效应的工具，以及 用于指导单独量身定制的早期干预措施，旨在防止与年龄相关的认知下降，MCI和AD。