Replication Data for: Dementia Risk and Dynamic Response to Exercise (DYNAMIC) NCT04009629

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 Alzheimer's disease (AD). 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 CBF and prompts neurotrophin release. These transient changes ultimately drive long-term physiologic adaptation to exercise. Therefore, the study team 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. The study team expects 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 the field can optimize biomarker measurement for future exercise intervention randomized controlled trials, informing our long-term goal of identifying precision exercise prescription for AD prevention.

大脑与心血管系统在高血压、高胆固醇血症及APOE4等遗传因素相关的衰老性疾病中，共享风险因子。正因这一关联，诸多研究聚焦于脑血管健康在降低痴呆风险中的作用。规律有氧运动对心血管健康的益处已得到充分证实，且多次被证明与更佳的认知功能、脑健康及更低的阿尔茨海默病（Alzheimer's disease, AD）发病风险相关。尽管已有充分证据表明有氧运动可带来持久的认知与脑健康获益，但有氧运动与脑健康、认知功能之间的关联机制仍未被精准阐明。在诸多潜在机制中，脑血流量（cerebral blood flow, CBF）以及神经营养因子等血液生物标志物，因其与脑健康和心血管健康存在共同关联，成为极具潜力的研究靶点。既往研究大多尝试在长期运动干预后的静息状态下测量这些机制的变化，但所得结果混杂且相互矛盾。此外，过往研究往往未考虑可能削弱运动效果的遗传差异。与既往研究不同，本研究的创新之处在于，首先表征急性运动负荷所引发的动态变化。单次有氧运动可暂时性提升脑血流量，并促使神经营养因子释放。这些一过性变化最终会驱动机体对运动产生长期生理适应。因此，本研究团队将纳入一组无痴呆症状的老年人群，表征其接受单次标准化急性有氧运动后的动态响应，并对比携带APOE4等位基因与未携带该基因的受试者。本研究的首要目标为验证：APOE4携带者在面对急性运动负荷时，其脑血流量响应是否会被削弱。第二项目标则类似地检验，相较于非携带者，APOE4携带者的血液生物标志物（如脑源性神经营养因子、胰岛素样生长因子及血管内皮生长因子）的急性运动响应是否存在差异。研究团队期望，精准阐明急性运动的效应，将为理解有氧运动如何支持认知功能与脑健康提供宝贵洞见。依托这一认知，该领域可优化未来运动干预随机对照试验中的生物标志物测量方案，从而助力我们的长期目标：为阿尔茨海默病预防制定精准运动处方。