Determinants of Individual Differences in the Efficacy of Aerobic Exercise to Improve Brain Health and Reduce Alzheimer Disease Risk in Older African Americans

有氧运动改善大脑健康和降低老年非裔美国人阿尔茨海默病风险的功效个体差异的决定因素

• 批准号: 10704183
• 负责人: MARK A GLUCK
• 金额: $ 94.32万
• 依托单位: RUTGERS THE STATE UNIV OF NJ NEWARK
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10704183
• 关键词: Aerobic Exercise; African American population; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid; Area; Behavior Therapy; Biological Markers; Biometry; Blood; Brain imaging; Brain region; Caring; Church; Clinic; Clinical Trials; Cognitive; Communities; Dancing; Data Analyses; Disparity; Dose; Education; Elderly; Enrollment; Equilibrium; Exercise; Foundations; Frequencies; Functional Magnetic Resonance Imaging; Future; General Population; Genes; Genetic Determinism; Genetic Risk; Genotype; Goals; Health; Hematological Disease; Heterogeneity; Impairment; Individual Differences; Intervention; Kinesiology; Knowledge; Learning; Light; Longevity; Low income; Magnetic Resonance Imaging; Measures; Medial; Mediating; Medical; Memory impairment; Neighborhoods; Neurology; Participant; Phase; Physicians; Population; Prevalence; Privatization; Public Health; Public Housing; Ramp; Randomized; Recommendation; Research; Rest; Risk; Risk Reduction; Running; Safety; Sample Size; Scientist; Source; Symptoms; Temporal Lobe; Testing; Time; Variant; Work; active control; behavioral clinical trial; brain health; burden of illness; caucasian American; cognitive benefits; cognitive testing; cost; dementia risk; exercise intervention; exercise prescription; exercise program; experience; fitness; fitness intervention; flexibility; group intervention; health assessment; health determinants; health disparity; high risk; improved; intervention effect; neural; neurofilament; neuroprotection; novel; post intervention; power analysis; pre-clinical; primary outcome; programs; recruit; response; risk variant; sedentary; social; social determinants; tau Proteins

PROJECT SUMMARY/ABSTRACT Older African Americans—especially those with lower income and those living in urban neighborhoods— have a greater risk of Alzheimer’s disease (AD) compared to the general population. This health disparity is attributable, in part, to modifiable factors including insufficient levels of aerobic exercise. However, not everyone gains the same degree of neuroprotection from exercise. For the proposed project, we plan to investigate genetic risk as a novel source of response heterogeneity to exercise interventions in African Americans. Previously, we demonstrated that five months of twice-weekly cardio-dance exercise can increase the dynamic rearrangement (or “neural flexibility”) of resting-state networks within the medial temporal lobe (MTL), one of the earliest brain regions impacted by AD. Moreover, this improved neural flexibility mediates intervention-related improvements in generalization, the ability to apply past learning to novel task demands. Given our earlier findings that generalization is impaired in preclinical AD, these results suggest a novel circuit-level mechanism, MTL neural flexibility, through which exercise may reduce risk for dementia. Moreover, we discovered that the cognitive benefits of exercise in older African Americans are diminished in those with a risk variant of the ABCA7 (rs3764650) gene. Two key limitations to our previous exercise studies were: (1) interventions limited to two 60-minute classes/week, below the recommended 150 minutes/week, and (2) too few participants to evaluate the effect of ABCA7 on exercise-induced changes on neural flexibility. We propose to recruit 280 sedentary older African Americans, ages 60 and above, to be randomized to one of two equally engaging six-month interventions, a Cardio Dance Fitness (CDF) intervention, and a Strength, Flexibility, & Balance active control. All participants will undergo—at enrollment and post-intervention—health assessments, cognitive tests, and structural and functional magnetic resonance imaging (fMRI), and a blood-draw to assess amyloid (A𝛽 42/40) and tau (p-tau231, p-tau181). This will enable us to test: 1) the effect of the CDF intervention on a cognitive marker of AD risk, generalization; 2) the effect of the CDF intervention on a fMRI biomarker of AD, neural flexibility, and determine whether improvements in neural flexibility mediate improvements in generalization; and 3) whether ABCA7 genotypic variations moderate the efficacy of the CDF intervention for reducing AD risk. Impact: This work lays the foundation for future larger clinical trials to develop personalized exercise prescriptions for older African Americans with varying genetic, health, and social-determinant risk profiles, so as to optimize the impact of this low-cost non-pharmaceutical intervention for improving their brain health.

项目摘要/摘要 年长的非洲裔美国人--特别是那些收入较低的人和生活在城市社区的人-- 与普通人群相比，患阿尔茨海默病(AD)的风险更大。这种健康差距是 部分可归因于可修改的因素，包括有氧运动水平不足。然而，不是 每个人都能从锻炼中获得相同程度的神经保护。就建议的项目而言，我们计划 在非洲调查遗传风险作为锻炼干预反应异质性的新来源 美国人。在此之前，我们证明了五个月的每周两次的有氧运动可以 增加内侧的静息状态网络的动态重排(或“神经灵活性”) 颞叶(MTL)，最早受AD影响的脑区之一。此外，这一改进的神经 灵活性调节了与干预相关的泛化改进，即将过去的学习应用于 新的任务要求。鉴于我们早先的发现，临床前AD患者的泛化能力受损，这些结果 提出一种新的电路级机制，MTL神经灵活性，通过这种机制，运动可能会降低患上 痴呆症。此外，我们发现，锻炼对老年非裔美国人的认知益处是 在携带ABCA7(Rs3764650)基因风险变异的人中减少。我们之前的两个关键限制 运动研究是：(1)干预限于每周两节60分钟的课程，低于推荐的150分钟 每周每分钟，以及(2)太少的参与者来评估ABCA7对运动诱导的变化的影响 神经灵活性。我们建议招募280名60岁及以上、久坐不动的非洲裔美国人 随机分为两种同样引人入胜的干预措施之一，为期六个月的心脏舞蹈健身(CDF) 干预，和一种力量、灵活、平衡的主动控制。所有参与者将在注册时接受 和干预后--健康评估、认知测试、结构和功能磁化 磁共振成像(FMRI)和抽血评估淀粉样蛋白(A𝛽42/40)和tau(p-tau231，p-tau181)。这 将使我们能够测试：1)CDF干预对AD风险的认知标记物泛化的影响；2) CDF干预对AD的fMRI生物标志物、神经灵活性的影响，并确定 神经灵活性的改善中介泛化能力的改善；以及3)ABCA7基因型别是否 变异使CDF干预降低AD风险的有效性减弱。影响：这项工作奠定了 为未来更大规模的临床试验奠定基础，为非洲老年人开发个性化运动处方 具有不同遗传、健康和社会决定因素风险特征的美国人，以优化 这种低成本的非药物干预可以改善他们的大脑健康。