Brain and behavioral correlates of fitness, cerebrovascular health and aging

描述(由申请人提供)：本申请涉及广泛的挑战领域(01)行为，行为改变，以及预防和特定挑战主题，01-AG-102：行为改变的神经机制。正常老龄化中的认知衰退是一个非常重要的社会问题，影响着全球数百万人。具体地说，正常衰老伴随着工作记忆和执行功能/注意力控制能力的下降，以及长期记忆和处理速度的下降。因此，增加对年龄相关认知障碍的可能预测因素及其相互作用的了解，可以提供早期发现的手段，从而提高成功预防和/或治疗的机会，从而产生巨大的社会和经济效益。最近的研究强调，体育锻炼和健身可能有助于延缓衰老对认知的一些影响，特别是那些与工作记忆和执行功能有关的影响，尽管获得这些收益的确切机制尚未完全了解。在这项工作中，我们将详细调查脑血管系统的健康状况可能对身体健康对大脑解剖和功能以及认知表现的有益影响所起的中介作用。我们的方法是基于这样的假设，即所有正在研究的现象(身体健康/活动、脑血管健康、大脑解剖和功能以及认知功能)实际上都是复杂的和多方面的，最好使用多变量方法进行研究。因此，针对其中的每一个，我们在多个层面采取多项措施。我们将在一个包括四个年龄组(50-60岁、60-70岁、70-80岁和80-90岁)的正常衰老成年人样本中调查自然发生的变异性，这些年龄组将在12个月间隔内测量两次(因此提供横断面和短期纵向分析)。将使用基于磁共振成像、扩散近红外光谱成像和电生理方法的多模式成像方法来提供脑血管状态以及大脑解剖和功能的地图。社会影响。老龄化导致的认知衰退影响着全球数百万人。及早发现它可能导致预防和改进干预做法，从而在经济和人道主义方面为社会带来不可估量的好处。体力活动制度已被证明有益于认知老化。因此，更好地了解这些利益的积累机制具有巨大的现实意义。此外，根据2009年ARRA关于这些挑战提案的指导方针，我们强调，如果获得资金，这项提案将产生一个新的职位(研究生研究助理)，并允许保留另外两个职位(高级研究科学家和研究专家)，否则可能会失去工作。进一步预计，通过这笔资金，这些研究人员将接受生物医学科学方面的宝贵培训，这将使他们在未来的就业市场上更具竞争力。 与公共健康相关：老龄化中的认知衰退影响着全球数百万人。及早发现它可能导致预防和改进干预做法，从而在经济和人道主义方面为社会带来不可估量的好处。体力活动制度已被证明有益于认知老化。因此，更好地了解这些利益的积累机制具有巨大的现实意义。此外，根据2009年ARRA关于这些挑战提案的指导方针，我们强调，如果获得资金，这项提案将产生一个新的职位(研究生研究助理)，并允许保留另外两个职位(高级研究科学家和研究专家)，否则可能会失去工作。进一步预计，通过这笔资金，这些研究人员将接受生物医学科学方面的宝贵培训，这将使他们在未来的就业市场上更具竞争力。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (01) Behavior, Behavioral Change, and Prevention and specific Challenge Topic, 01-AG-102: Neural mechanisms of behavioral change. Cognitive decline in normal aging is a very important societal problem, which impacts millions of people worldwide. Specifically, normal aging is accompanied by declines in working memory and executive function/attention control, as well as in long term memory and speed of processing. Thus, increasing knowledge about the possible predictors of age- related cognitive impairments and their interactions can yield substantial societal and economic benefits, by providing means of early detection and thus improving the chances of successful prevention and/or treatment. Recent studies have emphasized that physical activity and fitness may help stave off some of the effect of aging on cognition, and specifically those related to working memory and executive function, although the exact mechanisms through which these gains are obtained are not yet completely understood. In this work we will conduct a detailed investigation of the possible mediating role that the health status of the cerebrovascular system may have on the beneficial effects of physical fitness on brain anatomy and function and cognitive performance. Our approach is based on the assumption that all the phenomena under study (physical fitness/activity, cerebrovascular health, brain anatomy and function, and cognitive function) are in fact complex and multifaceted and best studied using a multivariate approach. Therefore, for each of them, we take multiple measures at multiple levels. We will investigate naturally-occurring variability in a sample of normally-aging adults comprising four age groups (50-60, 60-70, 70-80, and 80-90 years old), which will be measured twice at 12 months distance (thus affording both cross-sectional and short-term longitudinal analyses). A multimodal imaging approach based on a combination of magnetic resonance imaging, diffusive near-infrared spectroscopic imaging, and electrophysiological methods will be used to provide maps of both cerebrovascular status and brain anatomy and function. Societal Impact. Cognitive decline in aging affects millions of people worldwide. Its early detection may lead to prevention and improvement in intervention practices, thus providing incalculable benefits to society both in economic and humanitarian terms. Physical activity regimes have shown to be beneficial to cognitive aging. Therefore, a better understanding of the mechanisms through which these benefits are accrued is of enormous practical significance. In addition, following the guidelines of ARRA 2009 for these Challenge proposals, we underscore the fact that this proposal, if funded, will generate one new position (graduate research assistant) and allow for the retention of two additional positions (senior research scientist and research specialist) who may otherwise lose employment. It is further expected that, through this funding, these investigators will receive valuable training in the biomedical sciences, which will make them more competitive on job market in the future. PUBLIC HEALTH RELEVANCE: Cognitive decline in aging affects millions of people worldwide. Its early detection may lead to prevention and improvement in intervention practices, thus providing incalculable benefits to society both in economic and humanitarian terms. Physical activity regimes have shown to be beneficial to cognitive aging. Therefore, a better understanding of the mechanisms through which these benefits are accrued is of enormous practical significance. In addition, following the guidelines of ARRA 2009 for these Challenge proposals, we underscore the fact that this proposal, if funded, will generate one new position (graduate research assistant) and allow for the retention of two additional positions (senior research scientist and research specialist) who may otherwise lose employment. It is further expected that, through this funding, these investigators will receive valuable training in the biomedical sciences, which will make them more competitive on job market in the future.