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

血液生物标志物作为遗忘性轻度认知障碍有氧运动和/或认知训练治疗反应的替代终点

基本信息

批准号：
10572816
负责人：
Danni Li
金额：
$ 23.57万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2023-05-31
项目状态：
已结题

项目摘要

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.

项目摘要母体R01的目的是研究血液神经病理学和神经营养生物标志物对患有羊皮的轻度认知的老年人的3种干预措施的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；并结合有氧运动运动和认知训练（ACT）。该补品的第一个目标是提供财务来源，因此家长R01有足够的资金来利用ACT审判的修订的注册时间表保留父母R01在该奖项的原始范围内的总体影响。父r01建立在 ACT试验，一种多站点II期RCT，检查了6个月ACT干预的协同作用认知和MRI生物标志物（n = 128）。该法案审判因联盟而在2020年3月暂停了招生。 19在罗切斯特大学（UR）和明尼苏达大学（UMN）地点的研究关闭。我们无法在2020年将参与者招募参加ACT审判。该法案试验重新配置了其研究时间表由于入学率停顿而导致的招聘期损失。它还在亚利桑那州添加了第三个研究站点州立大学（ASU）招募。它将其招聘期延长到2022年8月31日底停止招聘终止日期的2022年9月30日。所有数据收集将于2024年2月至3月结束。但是，父母R01将于2022年5月31日结束，并且没有足够的资金来利用 ACT审判的修订后的入学时间表。因此，我们需要这种行政补充来扩展招聘和数据收集期，以最大化样本量并完成父母的范围 R01。该补充的第二个目标是通过调查血液来增加父r01的影响神经炎症生物标志物作为对AMCI中3种干预措施的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簇蛋白调节神经炎症。此外，血液神经胶质原纤维酸性蛋白（GFAP）已成为神经炎症的生物标志物。该证据表明血液神经炎症血浆GFAP和簇等生物标志物可以作为干预运动的替代端点 - 相关的治疗反应。此添加在父r01的范围内。第一个的具体目标目标是：（1）。在计划截至2022年8月31日或 2022年9月30日，如果不符合2022年8月31日的入学目标；（2）。完成所有血液收集到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中的神经炎症生物标志物；（4）。评估血液神经炎症生物标志物作为替代物预测对AMCI干预措施的认知反应的终点。