US POINTER Neuroimaging Ancillary Study

项目概要/摘要 美国研究通过生活方式干预来保护大脑健康，以降低风险（美国 POINTER）是阿尔茨海默氏症协会赞助的一项3500万美元的多地点随机临床试验 调查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）对老年人2年认知轨迹的影响 老年痴呆症POINTER是仿照芬兰的FINGER试验建立的，该试验显示， 那些被分配到多领域生活方式干预组与健康教育组的人。指针将使用 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，鼓励健康的生活方式。高强度（“结构化”） 生活方式干预组将接受频繁的辅导和小组会议，以鼓励有氧运动 认知训练4天/周，坚持改良的地中海饮食，心血管风险 通过加强医疗监测减少。基于成功的手指结果， 鉴于高强度的认知训练， 干预和跨生活方式领域的协同效应的潜力。 然而，POINTER设计缺乏神经影像学测量来研究 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。 这项拟议的成像辅助研究利用母试验提供的独特资源， 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 对AD和脑血管病理生理学改变的干预作用。委员会还将审查 这些基线生物标志物是否可以预测对干预的认知反应， 这对精准医学在确定最有可能从这种方法中受益的人方面具有重要意义。AD 将通过PET成像（基线，2年）评估脑血管病理生理学，以测量β- 淀粉样蛋白和tau蛋白负荷，以及MR成像（基线、1年、2年），以测量脑形态学，白色 物质高信号和微结构完整性以及脑血流。 深入分析疾病生物标志物的生活方式变化对公众具有重要意义 考虑到目前的证据表明生活方式对大脑健康的有利影响， 老年人，掩盖了迄今为止所有其他药物治疗的结果。此外，委员会认为， 改变生活方式是一种负担得起且易于获得的方法，其健康益处超出了大脑 健康POINTER试验的一个关键和临床相关特征是其招募方法， 以社区为基础的地理和种族/族裔多样的样本，确保 干预措施将适用于大部分老年人。

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.