US POINTER Neuroimaging Ancillary Study

US POINTER 神经影像辅助研究

• 批准号: 9980256
• 负责人: SUSAN M LANDAU
• 金额: $ 1114.64万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9980256
• 关键词: Adherence; Adult; Aerobic Exercise; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Amyloid beta-Protein; Ancillary Study; Apolipoprotein E; Biological Markers; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Characteristics; Cognition; Cognitive; Communities; Dementia; Diet; Disease; Education; Elderly; Enrollment; Ensure; Exercise; Failure; Fingers; Finland; Functional disorder; Genotype; Geography; Group Meetings; Group Structure; Health; Health Benefit; Health education; Healthcare; Hippocampus (Brain); Image; Impaired cognition; Individual; Instruction; Intervention; Intervention Studies; Intervention Trial; Investigation; Life Style; Life Style Modification; Link; Magnetic Resonance Imaging; Measures; Medical; Mediterranean Diet; Memory impairment; Modeling; Monitor; Multiple Abnormalities; Parents; Participant; Pathologic; Pharmacologic Substance; Pharmacological Treatment; Physical Exercise; Positron-Emission Tomography; Public Health; Randomized; Randomized Clinical Trials; Recommendation; Recording of previous events; Research; Research Design; Resources; Risk; Risk Factors; Risk Reduction; Role; Sample Size; Sampling; Structure; Support Groups; Testing; Therapeutic; Time; Weight; White Matter Hyperintensity; Work; base; brain health; cardiometabolic risk; cardiovascular health; cardiovascular risk factor; cerebrovascular; clinically relevant; clinically significant; cognitive benefits; cognitive disability; cognitive function; cognitive training; cohort; dementia risk; design; ethnic diversity; exercise adherence; exercise training; good diet; group intervention; healthy lifestyle; high risk; improved; intervention effect; lifestyle intervention; morphometry; neuroimaging; precision medicine; prevent; racial and ethnic; recruit; response; sedentary lifestyle; social; success; symposium; tau Proteins; tau aggregation; treatment as usual

Project Summary / Abstract The U.S. study to PrOtect brain health through lifestyle INTErvention to Reduce risk (U.S. POINTER) is a $35M Alzheimer's Association-sponsored multisite randomized clinical trial investigating the influence of a multidomain lifestyle intervention (exercise, diet, cognitive stimulation, health coaching for risk factor reduction) on 2yr cognitive trajectories in older adults at increased risk of dementia. POINTER was modeled after Finland's FINGER trial that showed a greater cognitive benefit for those assigned to a multidomain lifestyle intervention group versus health education. POINTER will use a similar two-group study design. The health education (“self-guided”) group will receive information and support through twice yearly group meetings to encourage healthy lifestyle practices. The higher-intensity (“structured”) lifestyle intervention group will receive frequent coaching and group meetings to encourage aerobic exercise and cognitive training 4 days/week, adherence to a modified Mediterranean diet, and cardiovascular risk reduction through increased medical monitoring. Based on the successful FINGER results, the structured group is predicted to show the greatest benefits on 2yr cognitive trajectories given the high intensity of the intervention and the potential for synergistic effects across lifestyle domains. Lacking from the POINTER design, however, are neuroimaging measures to investigate intervention effects on underlying Alzheimer's disease (AD) and cerebrovascular pathophysiology. This proposed imaging ancillary study leverages unique resources provided by the parent trial to examine whether changes in lifestyle can protect brain health and alter AD trajectories. The study will assess these intervention effects on changes in AD and cerebrovascular pathophysiology. It will also examine whether these biomarkers at baseline predict cognitive response to the intervention, which has important implications for precision medicine in identifying those most likely to benefit from this approach. AD and cerebrovascular pathophysiology will be assessed with PET imaging (baseline, 2yrs) to measure beta- amyloid and tau burden, and MR imaging (baseline, 1yr, 2yrs) to measure brain morphometry, white matter hyperintensities and microstructural integrity, and cerebral blood flow. An in-depth analysis of lifestyle changes on disease biomarkers has significant implications for public health given the current weight of evidence showing favorable effects of lifestyle on brain health in older adults that overshadow the results of all other pharmacological treatments to date. Moreover, lifestyle modification is an affordable and accessible approach with health benefits that extend beyond brain health. A critical and clinically relevant feature of the POINTER trial is its recruitment approach which targets a community-based and geographically and racially/ethnically diverse sample, ensuring that the intervention will be applicable to a large proportion of older individuals.

项目概要/摘要 美国研究通过生活方式干预降低风险来保护大脑健康（U.S. POINTER）是一项由阿尔茨海默病协会资助的 3500 万美元的多中心随机临床试验 研究多领域生活方式干预（运动、饮食、认知刺激、 降低风险因素的健康指导）对高风险老年人 2 年认知轨迹的影响 痴呆症。 POINTER 是仿照芬兰的 FINGER 试验而设计的，该试验显示了对认知能力的更大益处 那些被分配到多领域生活方式干预组的人与健康教育组的比较。 POINTER 将使用 类似的两组研究设计。健康教育（“自我指导”）小组将获得信息和支持 通过每年两次的小组会议来鼓励健康的生活方式。更高强度（“结构化”） 生活方式干预小组将接受频繁的辅导和小组会议，以鼓励有氧运动 每周 4 天的认知训练、坚持改良的地中海饮食以及心血管风险 通过加强医疗监测来减少。基于成功的 FINGER 结果，结构化 鉴于高强度的训练，预计该组在 2 年认知轨迹上表现出最大的益处 干预以及跨生活方式领域协同效应的潜力。 然而，POINTER 设计缺乏用于研究的神经影像学措施 对潜在的阿尔茨海默病（AD）和脑血管病理生理学的干预作用。 这项拟议的影像辅助研究利用母试验提供的独特资源来检查 生活方式的改变是否可以保护大脑健康并改变 AD 轨迹。该研究将评估这些 干预对 AD 和脑血管病理生理学变化的影响。它还将检查 这些基线生物标志物是否可以预测对干预的认知反应，这已经 对于精准医学确定最有可能从这种方法中受益的人来说具有重要意义。广告 脑血管病理生理学将通过 PET 成像（基线，2 年）进行评估，以测量 β- 淀粉样蛋白和 tau 蛋白负荷，以及用于测量大脑形态测量的 MR 成像（基线、1 年、2 年），白色 物质高强度和微观结构完整性以及脑血流量。 深入分析生活方式改变对疾病生物标志物的影响对公众具有重大意义 鉴于目前有大量证据表明生活方式对大脑健康有有利影响 迄今为止，老年人的所有其他药物治疗的结果都黯然失色。而且， 改变生活方式是一种负担得起且容易获得的方法，其健康益处不仅限于大脑 健康。 POINTER 试验的一个关键且与临床相关的特征是其招募方法，其目标是 以社区为基础且具有地域和种族/族裔多样性的样本，确保 干预措施将适用于很大一部分老年人。