Examining a dose-dependent exercise intervention on cerebrovascular plasticity in late adulthood

检查剂量依赖性运动干预对成年晚期脑血管可塑性的影响

• 批准号: 10711836
• 负责人: Tae Kim
• 金额: $ 46.71万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10711836
• 关键词: Address; Adult; Aerobic Exercise; Age Years; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Area; Blood flow; Brain; Cognition; Cognitive; Data; Data Analyses; Dementia; Deterioration; Diabetes Mellitus; Dose; Elderly; Exercise; Funding; Growth; Health Status; Hypertension; Impaired cognition; Intervention; Intervention Trial; Link; Mediating; Methods; Mission; Neurocognition; Participant; Phase; Preventive; Public Health; Public Policy; Randomized; Recommendation; Research; Risk Reduction; Stretching; Structure; Testing; Therapeutic; Training; United States National Institutes of Health; age related; biological sex; brain health; cerebral atrophy; cerebrovascular; cohort; cost effective; dosage; exercise intervention; improved; post intervention; prevent; randomized, clinical trials; response; risk mitigation; tau Proteins; vascular cognitive impairment and dementia

Abstract: Aerobic exercise (AE) is one of the most promising, accessible, and cost-effective methods for reducing risk for Alzheimer's disease (AD) and related dementias (ADRD), and for improving brain health and cognition in older adults. However, we do not fully understand the mechanisms by which AE-induced changes in the brain improve cognition and reduce the likelihood of transitioning to cognitive impairment. Cerebrovascular alterations progress with aging and have been identified as one of the primary factors associated with cognitive decline. Therefore, one leading hypothesis is that AE can modify aging-associated cerebrovascular deteriorations by accumulating long-term adaptations through repeated training sessions. These cerebrovascular changes could mediate improvements in structure and function in the brain, and associate with cognitive improvement. However, we still do not fully understand these possible mechanisms, nor the most effective doses to maximize cerebrovascular improvements. In order to assess cerebrovascular changes and their relationship with structural and functional brain changes in response to an AE intervention, we propose to conduct a secondary data analysis using a Phase III randomized clinical trial (RCT) of aerobic exercise called Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE). The IGNITE study included pre- and post-intervention assessments from a 12-month supervised exercise intervention in 648 cognitively normal adults between 65 and 80 years of age. Participants were randomized to one of 3 different dosage groups (n=213 each): (i) a moderate intensity AE of 150 min/week (the public-health recommended dose), (ii) a moderate intensity AE condition of 225 min/week, and (iii) a stretching control condition of 150 min/ week. We will test (1) whether a 12-month RCT of AE modifies cerebrovascular pulsatility and blood flow and whether these changes mediate improvements in cognition, (2) whether AE- induced cerebrovascular changes mediate improvements in brain atrophy, functional connectivity, and reduce WMH growth. We will also test whether any effects are associated with pre-existing health status, such as hypertension and type2 diabetes, which are associated with risk for AD/ADRD and linked to AD pathology (e.g. Ab and tau) . We will also examine whether biological sex moderates the results found in aims 1 and 2. We hypothesize that the group receiving 225 min/week will show the greatest cerebrovascular improvements and that these improvements mediate structural and functional brain changes. We also expect that the cerebrovascular improvements with AE will occur in region-specific manner and lead to domain-specific cognitive improvements that are related to those areas. This proposal employs a highly cost-effective approach by focusing on the secondary data analysis of an NIH-funded RCT and is therefore in line with the NIA mission to use data from existing cohorts to address important questions about how exercise prevents cognitive decline in late life. These findings could establish a framework for managing age-related cerebrovascular changes by participation in regular AE and could provide public policy guidance for using exercise as an approach for mitigating risks associated with vascular contributions to cognitive impairment and dementia (VCID). The results from this research could also lead to more effective preventive and therapeutic strategies to decrease the burden of AD/ADRD.

抽象的： 有氧运动（AE）是减少最有前途，可访问和成本效益的方法之一 阿尔茨海默氏病（AD）和相关痴呆症（ADRD）的风险，以及改善大脑健康和认知 在老年人中。但是，我们不完全了解AE诱导的变化的机制 大脑改善认知并减少过渡到认知障碍的可能性。脑血管 随着衰老的发展，变化已被确定为与认知相关的主要因素之一 衰退。所以， 一个主要假设是AE可以修改与衰老相关的脑血管 恶化 通过重复培训会议积累长期适应。这些 脑血管变化可以介导大脑结构和功能的改善，并介导 随着认知的改善。但是，我们仍然没有完全理解这些可能的机制，也不是 最有效的剂量以最大化脑血管改善。为了评估脑血管变化 以及它们与AE干预响应的结构和功能性大脑变化的关系，我们 提议使用有氧运动的III期随机临床试验（RCT）进行二级数据分析 在运动干预试验（IGNITE）中，练习称为神经认知中的收益。这 IGNITE研究包括12个月监督运动的干预前和干预后评估 在65至80岁之间进行648名认知正常成年人的干预。参与者是随机的 3个不同剂量组之一（n = 213个）：（i）每周150分钟的中等强度AE（公共卫生 建议的剂量），（ii）中等强度AE/周的中等强度AE条件，以及（iii）拉伸控制 条件为150分钟/周。我们将测试（1）12个月的AE是否修饰脑血管 脉动和血流以及这些变化是否介导了认知的改善，（2）是否ae- 诱导的脑血管变化介导了大脑萎缩，功能连通性的改善，并降低 WMH增长。我们还将测试是否与现有的健康状况相关，例如 高血压和 Type2糖尿病，与AD/ADRD风险相关并与AD病理有关（例如， AB和Tau） 。我们还将检查生物学是否在目标1和2中找到结果。 我们 假设接受225分钟/周的小组将显示最大的脑血管改善，并且 这些改进介导了结构和功能性大脑的变化。我们也期望 AE的脑血管改善将以特定于区域的方式进行，并导致特异性领域 与这些领域相关的认知改进。该提案采用了高度成本有效的方法 通过专注于NIH资助的RCT的二级数据分析，因此与NIA任务一致 使用现有队列的数据来解决有关运动如何阻止认知下降的重要问题 在后期。这些发现可以通过 参与常规AE，可以为使用锻炼作为方法提供公共政策指导 减轻与认知障碍和痴呆（VCID）的血管贡献相关的风险。这 这项研究的结果还可能导致更有效的预防和治疗策略，以减少 广告/adrd的负担。