Longitudinal Investigation of Cardiorespiratory Fitness and AD Biomarkers in an At-Risk Cohort

高危人群心肺健康和 AD 生物标志物的纵向调查

基本信息

批准号：
10064984
负责人：
OZIOMA C OKONKWO
金额：
$ 93.14万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-01-15 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10064984
关键词：
Abate Accelerometer Address Adult Aerobic Exercise Aging Alzheimer disease prevention Alzheimer&apos s Disease Alzheimer&apos s disease model Alzheimer&apos s disease risk Alzheimer&apos s disease therapy Alzheimer’s disease biomarker Amyloid beta-Protein Attention Attenuated Biological Markers Blood Vessels Cerebrovascular Circulation Clinical Clinical Trials Cognition Cognitive Cohort Studies Conflict (Psychology)Data Dementia Dependence Disease Elderly Enrollment Epidemic Etiology Evaluation Exercise Test Failure Family Financial compensation Functional disorder Future Gap Junctions Genetic Risk Goals Hippocampus (Brain)Human Individual Investigation Knowledge Link Magnetic Resonance Imaging Measures Mediating Nerve Degeneration Participant Pathogenicity Patient Self-Report Peripheral Persons Pharmacotherapy Phenotype Physical activity Physiological Play Positioning Attribute Positron-Emission Tomography Public Health Recording of previous events Registries Research Resources Risk Role Seminal Spinal Puncture Sum Symptoms Target Populations Testing Therapeutic Transducers Wisconsin Work abeta deposition active lifestyle age related animal data arterial stiffness baby boomer brain volume cardiorespiratory fitness cohort effective therapy epidemiology study glucose metabolism hippocampal atrophy insight insulin sensitivity longitudinal design middle age mild cognitive impairment multimodality neuroprotection novel prevent prospective resilience sex tau Proteins tau phosphorylation β-amyloid burden

项目摘要

PROJECT SUMMARY/ABSTRACT Currently-available drug treatments for Alzheimer's disease (AD) are not curative. Furthermore, findings from clinical trials testing novel disease-modifying therapeutics have been disappointing. Accordingly, the urgency of alternative approaches for halting the global crisis posed by AD cannot be overstated. Although data from cohort and epidemiological studies have long suggested a strong link between physical activity and dementia due to AD, the question of whether physical activity modulates the underlying pathophysiology of AD has only recently begun receiving attention. While the emerging evidence appears overall supportive of such a role for physical activity, several critical knowledge gaps persist. First, past studies have been largely cross-sectional. This leaves unresolved the possibility that observed effects simply reflect reverse causation. Second, “physical activity” has been assessed via a variety of approaches including self-report, activity trackers, and maximal graded exercise testing, leading to conflicting findings. Third, because past research has primarily been done in elderly persons, little is known about the potential influence of physical activity on AD risk in midlife, when most AD-related changes begin. Lastly, there is need for a better understanding of the mechanisms by which physical activity exerts its salutary effects. To address these gaps in knowledge (1) we focus this project on cardiorespiratory fitness (CRF), which constitutes the physiological nexus for *habitual* physical activity, (2) we employ a longitudinal design, which would allow us rigorously exclude the possibility of reverse causation, (3) we study a cohort of late-middle-aged adults who are, in principle, potentially only at the inceptive stages of AD, and (4) we investigate vascular and glucoregulatory function as viable transducers of the link between CRF and AD pathophysiology. Importantly, because the participants targeted for this study are being followed longitudinally through the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center, we will be uniquely positioned in the long term to elucidate the impact of midlife CRF on clinical endpoints of mild cognitive impairment and dementia. In sum, the multimodal and integrative study proposed here stands to provide critical insights into CRF as a potentially viable therapeutic for altering disease trajectory in the early stages of AD, prior to pervasive neurodegeneration, thereby delaying the emergence of clinical symptoms.

项目摘要/摘要目前可用于阿尔茨海默氏病（AD）的药物治疗不现代。此外，发现的结果测试新型疾病改良疗法的临床试验令人失望。根据停止由广告定位的全球危机的替代方法不能被夸大。虽然来自数据队列和流行病学研究长期以来一直表明体育活动与痴呆之间有着密切的联系由于AD，身体活动是否调节AD的基本病理生理学的问题仅具有最近开始受到关注。虽然新兴证据似乎总体上支持了这种作用体育活动，几个关键知识差距持续存在。首先，过去的研究在很大程度上是横断面的。这使观察到的效应仅反映了相反的原因的可能性。第二，“身体活动已通过多种方法进行评估，包括自我报告，活动跟踪器和最大分级运动测试，导致发现相互矛盾。第三，因为过去的研究已经完成在老年人中，当体育锻炼对中年的AD风险的潜在影响，当大多数与广告相关的更改开始。最后，需要更好地了解其机制体育活动发挥其有益的影响。为了解决知识中的这些差距（1），我们将这个项目集中在心肺健身（CRF），构成 *习惯 *体育活动的物理联系，（2）我们采用了纵向设计，这将使我们严格排除逆向原因的可能性，（3）我们研究了一个中间年龄的成年人的队列，原则上可能仅处于 AD，（4）我们研究了血管和葡萄糖调节功能，作为在 CRF和AD病理生理学。重要的是，因为遵循了针对这项研究的参与者通过威斯康星州的阿尔茨海默氏症和威斯康星州阿尔茨海默氏症的纵向登记登记处疾病研究中心，我们将在长期内独特地定位，以阐明中年的影响 CRF关于轻度认知障碍和痴呆症的临床终点。总之，多模式和集成这里提出的研究旨在为CRF提供关键的见解，以此作为改变的潜在可行疗法疾病轨迹在AD的早期阶段，在普遍神经变性之前，从而延迟了临床症状的出现。