Dementia Risk and Dynamic Response to Exercise

摘要 大脑和心血管系统共享与年龄有关的疾病的共同风险因素，例如 高血压、高胆固醇血症和遗传学(如APOE4)。由于这种联系，许多工作都集中在 论脑血管健康在降低痴呆风险中的作用。定期的有氧运动已经很好地确立了 有益于心血管健康，并一再被认为与更好的认知、大脑健康和更低的 患痴呆症的风险。尽管有强有力的证据表明持续的认知和大脑结果，但与 有氧运动与大脑健康和认知的关系仍然没有明确的定义。在众多潜力中 机制、脑血流量(CBF)和基于血液的生物标志物，如神经营养因子，是很有前途的 它们与大脑和心血管健康的共同联系的目标。之前的调查主要是 在长时间的运动后，尝试测量静息状态下这些机制的变化 干预措施的结果好坏参半，相互矛盾。此外，研究往往没有考虑到基因 可能会削弱锻炼效果的差异。与以前的工作不同，我们的创新方法是从 描述由于剧烈运动挑战而产生的动态变化。单轮有氧运动 运动暂时增加脑血流量(CBF)并促进神经营养素的释放。这些瞬变 变化最终会促使人们对运动进行长期的生理适应。因此，我们将描述 一组非痴呆老年人对急性标准化有氧运动的动态反应， 比较那些携带和不携带APOE4等位基因的人。第一个目标是测试CBF对急性脑出血的反应 运动挑战在APOE4携带者中变得迟钝。第二个目标同样将测试急性运动反应。 基于血液的生物标记物，如脑源性神经营养因子、胰岛素样生长因子和血管 APOE4携带者与非携带者中的内皮生长因子。最后，我们将探讨 CBF的急剧变化与我们基于血液的生物标记物和认知表现有关。我们预计会有更多 准确地了解急性影响将为有氧运动如何支持 认知功能和大脑健康。有了这些知识，我们可以优化生物标记物的测量 未来的运动干预随机对照试验，告知我们识别精确度的长期目标 预防AD的运动处方。

Abstract The brain and cardiovascular system share common risk factors for age-related diseases such as hypertension, hypercholesterolemia, and genetics (e.g. APOE4). Because of this link, much work has focused on the role of cerebrovascular health in reducing dementia risk. Regular aerobic exercise has well-established benefits for cardiovascular health and has been repeatedly linked to better cognition, brain health, and lower risk of dementia. Despite strong evidence for sustained cognitive and brain outcomes, the mechanisms relating aerobic exercise with brain health and cognition remain imprecisely defined. Amongst many potential mechanisms, cerebral blood flow (CBF) and blood-based biomarkers, such as neurotrophins, are promising targets for their shared association to brain and cardiovascular health. Prior investigations have largely attempted to measure change in these mechanisms under resting conditions after an extended exercise intervention with mixed and conflicting results. Further, studies have often not accounted for genetic differences that may blunt the effect of exercise. Unlike prior work, our innovative approach is to begin by characterizing the dynamic changes that result from an acute exercise challenge. A single bout of aerobic exercise temporarily increases cerebral blood flow (CBF) and prompts neurotrophin release. These transient changes ultimately drive long-term physiologic adaptation to exercise. Therefore, we will characterize the dynamic response to an acute, standardized bout of aerobic exercise in a group of nondemented older adults, comparing those who do and do not carry the APOE4 allele. The first aim will test if CBF response to an acute exercise challenge is blunted in APOE4 carriers. The second aim will similarly test the acute exercise response of blood-based biomarkers such as brain derived neurotrophic factor, insulin-like growth factor, and vascular endothelial growth factor in APOE4 carriers versus non-carriers. Finally, we will explore the relationship of acute changes in CBF with our blood-based biomarkers and cognitive performance. We expect that more accurately understanding the acute effects will provide valuable insight into how aerobic exercise supports cognitive function and brain health. Armed with this knowledge we can optimize biomarker measurement for future exercise intervention randomized controlled trials, informing our long-term goal of identifying precision exercise prescription for AD prevention.