Ultra-high-field neuroimaging in elderly after a two-year exercise intervention

描述（由申请人提供）：老化的大脑在受到神经元死亡、血管异常和连接丧失影响的同时保持学习能力。对这种保留功能的一个可能解释是即使在晚年也能维持神经再生潜力。强有力的新兴人类体内证据表明，海马结构变得更大的身体活动（PA）的干预措施在功能良好的老年人在他们的六十年代后期。然而，目前尚不清楚非常年老和虚弱的人是否也对 PA与海马扩张和-如果他们这样做-变化是否保持超过一年。此外，尚不清楚海马变化是否特异于具有神经再生潜力的区域（齿状回），以及PA对相关脑血管和功能性脑测量的影响。解决老年人在知识上的这些差距将扩大我们对老年大脑可塑性的理解，特别是对干预的反应。 我们建议通过检查之前在年轻老年人海马结构中报告的PA相关影响是否存在于非常年老和虚弱的成年人中超过1年的时间段来解决这一知识差距，这些影响是否对齿状回，微循环和功能连接有意义。迄今为止，回答这些问题存在两个主要障碍：1）常规非侵入性成像不能精确测量齿状回; 2）非常老的成年人可能身体虚弱，并且不太可能长期参与和坚持PA程序。该提案通过在已经参与现有的长期随机临床试验的虚弱老年人中应用7特斯拉的无创超高场神经成像来解决这些障碍，该试验将步行与健康教育进行比较（成功老化：SA）。我们已经在2010年65例患者随机分组时获得了超高场脑部图像，并有资金在第2年随访时获得所有脑部MRI，估计样本量为n = 50例，在干预前后进行MRI，另外n = 30例仅在干预后进行MRI。这是一个处理和分析这些数据的应用程序：1）定量PA与超高场脑标志物（AIM1）的关系; 2）确定超高场脑标志物（AIM2）中PA相关变化的定位; 3）探索超高场标记物在解释PA脑反应（AIM 3）中的作用该建议具有很高的成功机会，因为它应用了先前验证的神经成像协议，以响应先前在该特殊人群中也已验证的PA干预类型。这是一个独特的机会，可以利用超高场脑MRI的现有数据，现有的招募、保留、干预和治疗的运营基础设施， 正在进行的LIFE研究的临床评估和LIFE领导团队的专业知识，本提案的Co-I。由于随机对照试验的高成本，这种高度先进的神经影像学和干预研究类型的结合不太可能再次发生。

DESCRIPTION (provided by applicant): The aging brain maintains the ability to learn while being affected by neuronal death, vascular abnormalities and connectivity loss. A possible explanation for this preserved function is the maintenance of neuroregenerative potential even in late-life. Strong emerging human in-vivo evidence indicates that the hippocampal formation becomes larger in response to physical activity (PA) interventions in well-functioning elderly in their late sixties. However, it is not known whether very old and frail individuals also respond to PA with hippocampal expansion and -if they do- whether changes remain beyond one year. Moreover, it is unknown whether hippocampal changes are specific for areas with neuroregenerative potential (the dentate gyrus), and the effects of PA on related cerebrovascular and functional brain measures. Addressing these gaps in knowledge in very old adults will expand our understanding of brain plasticity in very old age, specifically in response to intervention. We propose to address this gap in knowledge by examining whether the PA-related effects previously reported in the hippocampal formation of younger elderly exist in very old and frail adults for periods of time beyond 1 year, whether these effects are significant for the dentate gyrus, microcirculature and functional connectivity. To date, there have been two major barriers to answer these questions: 1) conventional non- invasive imaging cannot precisely measure the dentate gyrus; 2) very old adults are likely to be physically frail and unlikely to participate and adhere to a PA program for long period of times. This proposal addresses these barriers by applying non-invasive Ultra High-Field neuroimaging at 7Tesla in frail older adults who are already participating in an existing long-term randomized clinical trialof walking compared to health education (Successful Aging: SA). We have already acquired Ultra High-Field brain images at the time of randomization in 2010 in 65 ptc and have funds to acquire all brain MRI at the 2nd yr follow-up, for an estimated sample size of n=50 with MRIs pre and post-intervention and an additional n=30 with MRI at the post-intervention only. This is an application to process and analyze these data to: 1) Quantify the relationship of PA with Ultra High-Field brain markers (AIM1); 2) identify the localization of the PA-related changes in Ultra High-Field brain markers (AIM2); 3) Explore the role of Ultra High Field markers in explaining brain response to PA (AIM3).This proposal has a high chance of success because it applies previously validated neuroimaging protocols in response to a type of PA intervention that has also been previously validated in this special population. This is a unique opportunity to conduct this transformative study in a highly cost-effective design, leveraging existing data on Ultra High field brain MRIs, existing operational infrastructure for recruitment, retention, intervention, and clinical assessment of the ongoing LIFE study and the expertise of the LIFE leadership team, Co-I's of this proposal. Because of the high costs of RCTs, it is highly unlikely that this combination of highly advanced neuroimaging and type of intervention study will occur again.