Blood Biomarkers as Surrogate Endpoints of Treatment Responses to Aerobic Exercise and/or Cognitive Training in Amnestic Mild Cognitive Impairment

项目摘要 亲本R01的目的是研究血液中神经病理和神经营养生物标记物 3种干预措施对遗忘性轻度认知障碍老年人治疗反应的替代终点 损害(aMCI，AD的前驱阶段)：有氧运动；认知训练；复合有氧运动 运动和认知训练(ACT)。本补充文件的第一个目标是提供资金来源，因此 Parent R01有足够的资金利用修订后的ACT试验登记时间表 保留母公司R01‘S在原评奖范围内的整体影响。父R01构建在 ACT试验，一项多部位II期随机对照试验，研究为期6个月的ACT干预对患者的协同影响 认知和MRI生物标志物(n=128)。ACT试验于2020年3月暂停登记，原因是Covid- 19关闭罗切斯特大学(UR)和明尼苏达大学(UMN)的研究。我们 无法让参与者参加2020年的ACT试验。ACT试验已将其研究时间表重新配置为 说明因暂停注册而丢失的招聘期。它还在亚利桑那州增加了第三个研究地点 州立大学(ASU)招生。它将招聘期延长至2022年8月31日底，并以硬- 停止招聘截止日期为2022年9月30日。所有数据收集将于2024年2月至3月结束。 然而，父R01将于2022年5月31日结束，将没有足够的资金剩余来利用 修订后的ACT试验登记时间表。因此，我们需要这个行政补充来扩展 招聘和数据收集期间，以最大限度地扩大样本量并完成母公司的范围 R01。本补充的第二个目标是通过调查血液来增加父母R01‘S的影响 神经炎症生物标记物作为aMCI中3种干预治疗反应的替代终点。 神经炎症调节AD的疾病进展。此外，最近的证据表明，锻炼 通过血浆聚集素调节神经炎症。此外，血液中胶质纤维酸性蛋白(GFAP) 已经成为神经炎症的生物标志物。这一证据表明，血液神经炎 血浆GFAP和Clusterin等生物标志物可作为干预运动的替代终点- 相关治疗反应。此添加在父R01的范围内。第一个目标的具体目标 目标是：(1)。在计划于2022年8月31日进行的ACT试验后继续招募参与者，或 2022年9月30日前未达到招生目标的；(2)完成所有血液采集 到2024年3月。第二个目标的具体目标是：(3)。确定干预措施对血液的影响 AMCI中的神经炎性生物标志物；评估血液神经炎生物标记物作为替代指标 预测急性心肌梗死患者对干预措施的认知反应的终点。

Project Summary The objective of the parent R01 is to investigate blood neuropathological and neurotrophic biomarkers as surrogate endpoints for treatment responses to 3 interventions in older adults with amnestic mild cognitive impairment (aMCI, a prodromal stage of AD): aerobic exercise; cognitive training; and combined aerobic exercise and cognitive training (ACT). The first goal of this supplement is to provide financial sources, so the parent R01 has sufficient funding to take advantage of the revised enrollment timeline of the ACT Trial to preserve the parent R01's overall impact within the original scope of the award. The parent R01 is built on the ACT trial, a multi-site Phase II RCT that examines the synergistic effects of a 6-month ACT intervention on cognition and MRI biomarkers (n=128). The ACT Trial paused its enrollment in March 2020 due to the Covid- 19 shutdown of research at the University of Rochester (UR) and the University of Minnesota (UMN) sites. We could not enroll the participants in the ACT Trial in 2020. The ACT Trial has re-configured its study timeline to account for the lost recruitment period due to enrollment pause. It also added a 3rd study site at the Arizona State University (ASU) to recruit. It extended its recruitment period to the end of August 31, 2022, with a hard- stop recruitment ending date of September 30, 2022. All data collections will end on Feb-March 2024. However, the parent R01 will end on May 31, 2022, and will not have sufficient funding left to take advantage of the revised enrollment timeline of the ACT Trial. Hence, we need this administrative supplement to extend the recruitment and data collection period to maximize sample size and accomplish the scope of the parent R01. The second goal of this supplement is to increase the parent R01's impact by investigating blood neuroinflammation biomarkers as surrogate endpoints for treatment responses to 3 interventions in aMCI. Neuroinflammation modulates disease progression of AD. In addition, recent evidence suggests that exercise modulate neuroinflammation through plasma clusterin. Furthermore, blood glial fibrillary acidic protein (GFAP) has emerged as a biomarker for neuroinflammation. This evidence suggests that blood neuroinflammation biomarkers such as plasma GFAP and clusterin could serve as surrogate endpoints for intervention exercise- related treatment responses. This addition is within the scope of the parent R01. The specific aims for the first goal are: (1). Continue enrolling participants following the ACT Trial scheduled to August 31, 2022, or September 30, 2022, if not meeting the enrollment goal by August 31, 2022; (2). Complete all blood collections by March 2024. The specific aims for the second goal are: (3). Determine the effects of interventions on blood neuroinflammation biomarkers in aMCI; (4). Evaluate blood neuroinflammation biomarkers as surrogate endpoints for predicting cognitive responses to interventions in aMCI.