The effect of physical activity on cognition relative to APOE genotype (PAAD-II)

体力活动对与 APOE 基因型相关的认知的影响 (PAAD-II)

基本信息

批准号：
10169630
负责人：
JENNIFER L ETNIER
金额：
$ 3.67万
依托单位：
UNIVERSITY OF NORTH CAROLINA GREENSBORO
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 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10169630
关键词：
Address Adult Affect Age Alleles Alzheimer&apos s Disease Alzheimer&apos s disease risk Apolipoproteins Biological Biological Markers Blood specimen Cerebrum Cognition Cognitive Data Dose Early Intervention Elderly Family history of Funding Genetic Risk Genotype Incidence Individual Link Literature MRI Scans Magnetic Resonance Imaging Measures Mediation Neurologic Persons Phase Phase III Clinical Trials Physical activity Pre-Post Tests Prevalence Prevention strategy Prospective Studies Public Health Publishing Randomized Randomized Clinical Trials Randomized Controlled Trials Research Resources Rest Risk Role Structure Susceptibility Gene Testing United States United States National Institutes of Health Work apolipoprotein E-4 carrier status cognitive benefits cognitive performance disorder risk experience experimental study improved middle age neuroimaging phase II trial programs protective effect treatment as usual white matter

项目摘要

Project Summary: By 2050, the prevalence of Alzheimer’s disease (AD) in the United States is predicted to reach 13.8 million. Despite worldwide research efforts, a cure for AD has not been identified. Thus, it is critical to identify preventive strategies that can reduce the risk of or delay the onset of AD. Physical activity (PA) has potential in this regard. Meta-analytic reviews and our own experimental studies show that older adults who participate in PA experience larger gains in cognitive performance than do controls. Prospective studies also show that PA is associated with a lower risk of AD and that the relationship between baseline PA and subsequent cognitive performance is moderated by a susceptibility gene for AD (apolipoprotein, APOE). In a Phase I proof-of-concept trial, we showed that individuals with a family history of AD (FH+) achieve cognitive benefits in association with PA and that these benefits were even evident in those with a genetic risk for AD (i.e., APOE e4 carriers, APOE4+). However, no published randomized controlled trial has assessed the effects of PA on cognition in cognitively normal FH+ individuals relative to APOE4 status. In addition, in currently funded trials beginning to address this gap, the focus is on older adults (65+); thus limiting the ability to identify protective effects that may be more evident with earlier interventions. Lastly, current evidence does not elucidate mechanisms to explain how PA benefits cognitive performance. These gaps in the literature have motivated our Phase II trial, in which we extend our past work by proposing a randomized clinical trial to: (a) test the causal link between PA and cognitive performance in middle-aged adults (40-65 years) with a FH+, and (b) determine if the effect is moderated by APOE4 carrier status. We will collect neuroimaging measures of cerebral structure, white matter integrity, and resting state connectivity; assess putative biological markers; and (using moderated mediation analyses) increase understanding of underlying mechanisms and of the extent to which effects are moderated by APOE4 carrier status. To test our hypotheses, we will randomly assign 240 cognitively normal, middle-aged adults to a 1-year PA program or a usual care control. We will assess cognitive performance at pre-, mid-, and post-test, and obtain MRI scans and blood samples at pre- and post- test. We will examine the effects of PA on cognitive performance and on neurological and biological mechanisms and will explore the moderating role of APOE4. A strength of this study is that we incorporate cognitive measures and MRI sequences used in a Phase III clinical trial (1R01AG053952) testing the effects of PA on cognition in older adults (65-80 years), and we are collaborating with the PI of that trial (Erickson). This will allow us to leverage NIH’s resources by compiling data across a broad age range. Importantly, findings from this study may support PA as a means of improving cognitive performance by those with a heightened risk for AD. This could have public health implications, because delaying AD by 1 year could reduce its incidence by 11%.

项目摘要：到 2050 年，预计美国阿尔茨海默病 (AD) 的患病率将尽管全世界都在努力研究，但 AD 的治疗方法尚未找到，因此，治疗 AD 至关重要。确定可以降低 AD 风险或延缓 AD 发作的预防策略。荟萃分析评论和我们自己的实验研究表明，老年人在这方面具有潜力。与对照组相比，参与 PA 的认知表现也有更大的提高。表明 PA 与较低的 AD 风险相关，并且基线 PA 与 AD 之间的关系随后的认知表现受到 AD 易感基因（载脂蛋白，APOE）的调节。第一阶段概念验证试验表明，有 AD 家族史 (FH+) 的个体能够实现认知能力与 PA 相关的益处，这些益处对于那些有 AD 遗传风险的人来说甚至是显而易见的（即 APOE e4 携带者、APOE4+）但是，尚无已发表的随机对照试验评估其效果。 PA 对认知正常 FH+ 个体相对于 APOE4 状态的认知影响。资助的试验开始解决这一差距，重点是老年人（65 岁以上），从而限制了识别能力；最后，目前的证据表明，早期干预措施可能会产生更明显的保护作用。阐明机制来解释 PA 如何有益于认知表现。文献中的这些空白存在。激发了我们的 II 期试验，其中我们通过提出一项随机临床试验来扩展我们过去的工作：(a) 测试 FH+ 中年人（40-65 岁）的 PA 与认知表现之间的因果关系， (b) 确定该影响是否受到 APOE4 携带者状态的调节。我们将收集神经影像学指标。大脑结构、白质完整性和静息状态连接性；以及（使用有调节的中介分析）增加对潜在机制和程度的理解哪些影响受到 APOE4 携带者状态的调节为了检验我们的假设，我们将随机分配 240 名。我们将评估认知正常的中年人是否接受为期 1 年的 PA 计划或常规护理控制。测试前、测试中和测试后的认知表现，并在测试前和测试后获取 MRI 扫描和血液样本我们将检查 PA 对认知表现以及神经和生物学的影响。机制，并将探讨 APOE4 的调节作用。这项研究的优势在于我们将其纳入其中。 III 期临床试验 (1R01AG053952) 中使用的认知测量和 MRI 序列测试了 PA 对老年人（65-80 岁）的认知，我们正在与该试验的 PI (Erickson) 合作。将使我们能够通过编译广泛年龄范围的数据来利用 NIH 的资源。这项研究可能支持 PA 作为改善哮喘患者认知能力的一种手段这可能会对公共健康产生影响，因为将 AD 推迟一年可以降低其风险。发病率降低 11%。