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.

项目概要/摘要 年长的非裔美国人——尤其是那些收入较低的人和居住在城市社区的人—— 与普通人群相比，患有阿尔茨海默病 (AD) 的风险更大。 部分归因于可改变的因素，包括有氧运动水平不足，但并非如此。 每个人都可以从锻炼中获得相同程度的神经保护。 研究遗传风险作为非洲运动干预反应异质性的新来源 美国人之前，我们证明了五个月每周两次的有氧运动可以。 增加内侧静息态网络的动态重排（或“神经灵活性”） 颞叶 (MTL) 是最早受 AD 影响的大脑区域之一。此外，这还改善了神经功能。 灵活性介导了与干预相关的泛化能力的提高，即应用过去的学习的能力 鉴于我们早期的发现，临床前 AD 的泛化能力受到损害，这些结果 提出了一种新的电路级机制，即 MTL 神经灵活性，通过这种机制，锻炼可以降低以下风险： 此外，我们发现运动对老年非裔美国人的认知益处是 具有 ABCA7 (rs3764650) 基因风险变异的人的风险降低。我们之前的两个关键限制。 运动研究是：(1) 干预措施仅限于每周两节 60 分钟的课程，低于建议的 150 节 分钟/周，(2) 参与者太少，无法评估 ABCA7 对运动引起的变化的影响 我们建议招募 280 名 60 岁及以上久坐的老年非裔美国人， 随机接受两项同样有吸引力的六个月干预措施之一，即有氧舞蹈健身 (CDF) 所有参与者在注册时都将接受干预，以及力量、灵活性和平衡主动控制。 和干预后——健康评估、认知测试以及结构和功能磁力 磁共振成像 (fMRI) 和抽血评估淀粉样蛋白 (A𝛽 42/40) 和 tau (p-tau231、p-tau181)。 将使我们能够测试：1）CDF 干预对 AD 风险认知标记的影响，泛化； CDF 干预对 AD 的功能磁共振成像生物标志物、神经灵活性的影响，并确定是否 神经灵活性的改善介导泛化能力的改善；3) ABCA7 基因型是否良好 变化会影响 CDF 干预措施降低 AD 风险的效果。 影响：这项工作奠定了基础。 为未来更大规模的临床试验奠定基础，为非洲老年人制定个性化运动处方 具有不同遗传、健康和社会决定因素风险状况的美国人，以优化其影响 这种低成本的非药物干预措施可以改善他们的大脑健康。