Cognition and cerebrovascular function across the lifespan

描述（由申请人提供）：脑老化伴随着脑血管系统的变化，如血管壁硬度增加和血供减少，这是影响认知的潜在重要因素。此外，尽管功能性神经成像技术已经对大脑衰老的适应性提供了深刻的了解，但功能磁共振成像信号依赖于间接信号——氧合和血流的变化——来检测不同部位的神经激活强度。血管健康的年龄差异可能会影响血流，从而独立于神经变化而改变功能磁共振成像信号，这使功能磁共振成像结果的解释变得复杂。在过去的三年里，我们应用了几种新的血管成像技术（其中一些是由首席研究员陆汉章开发的），对220名年龄在20至89岁之间的健康受试者进行了终身采样，这些受试者是由陆汉章资助的R-21奖资助的。研究对象是达拉斯终身大脑研究（DLBS）的参与者，该研究是由丹尼斯·C·帕克（Denise C Park）获得优异奖资助的，旨在检查参与者的神经结构和功能以及认知行为。横断面数据表明，脑血管储备（CVR）是最具年龄敏感性的血管参数，其下降速度是静息脑血流（CBF）的三倍。cvr校正后的fMRI数据支持了当前fMRI文献中关于额叶皮层年龄相关的过度募集的观点，但也提醒说枕叶和内侧颞叶的激活减少可能是血管伪影。与我们的发现相反，Nyberg及其同事（2010）最近的一项研究得出了相反的结论，该结论基于纵向但未经校正的（CVR） fMRI信号。因此，本项目将专注于CVR，并收集原始队列的纵向随访数据（从初次访问开始延迟4年），以便获得纵向、cv校正的fMRI数据。目前的提案建立在我们之前的横断面研究的基础上，该研究表明了所提议工作的可行性以及我们团队的经验和出色的合作历史。该提案的具体目标是：1。测定24-93岁健康受试者脑血管储备（CVR）的纵向变化。2. 检查CVR矫正后纵向fMRI BOLD的变化。3. 检查CVR矫正在多大程度上改善fMRI信号与认知功能之间的关系。该研究的完成将为衰老文献提供最独特的数据集之一，其中包括认知、结构、功能、血管参数

DESCRIPTION (provided by applicant): Aging in brain is accompanied by changes in brain vasculature such as increased stiffness of vascular wall and reduced blood supply, potentially important factors in affecting cognition. Furthermore, although functional neuroimaging techniques have provided tremendous insight into the adaptability of the aging brain, the fMRI signal relies upon an indirect signal--changes in oxygenation and blood flow--to detect intensity of neural activation across different sites. It is likely that age differences in vascular health afect blood flow and thereby change fMRI signals independent of the neural changes, which complicates the interpretation of fMRI results. In past three years, we have applied several novel vascular imaging techniques (some developed by the Principal Investigator, Hanzhang Lu) to a lifespan sample of 220 healthy subjects aged 20 to 89 funded under an R-21 award to Hanzhang Lu. The subjects studied were participants in the Dallas Lifespan Brain Study (DLBS) which is funded as a MERIT Award to Denise C Park, examining neural structure and function, as well as cognitive behavior in participants. The cross-sectional data identified Cerebral Vascular Reserve (CVR) as the most age-sensitive vascular parameter, showing a decline that was three times faster than that of resting Cerebral Blood Flow (CBF). The CVR-corrected fMRI data supported the current fMRI literature of an age- related over-recruitment in the frontal cortex, but cautioned that the activation decrease in the occipital lobe and medial temporal lobe may be vascular artifacts. In contrast to our findings, a recent study by Nyberg and colleagues (2010) reached an opposite conclusion based on longitudinal but uncorrected (for CVR) fMRI signals. The present project will therefore focus exclusively on CVR and collect longitudinal, follow-up data in the original cohort (lag of 4 years from initial visit), so that longitudinal, CV-corrected fMRI data will be available. The present proposal builds upon our previous cross-sectional study, which demonstrates the feasibility of the proposed work as well as the experience and excellent collaboration history of our team. The specific aims of the proposal are: 1. Determine longitudinal changes in Cerebral Vascular Reserve (CVR) in a group of healthy subjects aged 24-93 years. 2. Examine longitudinal fMRI BOLD changes after CVR correction. 3. Examine the extent to which CVR correction can improve the relationship between fMRI signal and cognitive function. The completion of this study will provide one of the most unique datasets in aging literature where cognition, structural, functional, vascular parameters of the brain are collected in the same participants, allowing us to determine in a definitive way the role that cerebrovascular healthy plays in mediating BOLD signal and cognitive function across the lifespan.