Longitudinal Assessment of Physical Activity, Cerebral Glucose Metabolism, and Cognitive Function in an At-risk Cohort

项目摘要/摘要 目前，有超过570万美国人患有阿尔茨海默病(AD)。它的流行和 鉴于该国人口老龄化，预计未来几十年相关成本将增加两倍。因为 这一迫在眉睫的流行病，推迟了AD症状的出现，并遏制了潜在的 疾病进程已成为国家公共卫生的当务之急。将症状出现的时间推迟5分钟 多年可以将阿尔茨海默病的患病率降低一半。不幸的是，目前可用的治疗AD的药物是 不能治愈。制止反倾销带来的危机的替代办法的紧迫性怎么强调都不为过。 人们越来越认识到体力活动(PA)和预防阿尔茨海默病之间的联系。元分析 前瞻性研究的数据显示，那些在中年进行体育锻炼的人的比例为35% 认知衰退的风险降低，45%的人在晚年患AD的风险降低。鉴于以下方面的有益影响 PA对AD发病风险已有较好的研究，PA对AD病理生物标志物影响的研究 才刚刚开始。从我们发表的工作和其他小组的工作中出现的证据表明，PA是 与大脑健康的许多指标呈正相关，包括大脑的葡萄糖代谢。即便如此，在那里 仍然是我们知识中的严重差距。首先，大多数研究依赖于PA的自我报告测量 容易出现报道偏差的情况。第二，现有的研究在性质上是横截面的，因此， 我们目前还不知道PA基线水平如何影响AD生物标记物的发展轨迹。 同样重要的是，我们不知道PA随时间的变化在多大程度上符合AD的变化 生物标志物。因此，这项建议的目标是确定PA之间的纵向关系， 50例阿尔茨海默病高危人群的脑葡萄糖代谢和认知功能。我们最初研究的是这些 他在2013年对这些人进行了调查，现在建议将他们带回来进行为期5年的跟踪调查。我们的中心假设是 大脑葡萄糖代谢和认知的纵向轨迹将随着中等强度的变化而变化 爸。我们将用两个具体的目标来检验我们的假设：目标1：调查纵向关系 PA与脑葡萄糖代谢之间的关系及目标2：研究纵向关系 PA和认知功能之间的关系。我们预测：1)中等强度PA的参与度表现为 基线(5年前)对大脑纵向葡萄糖代谢和认知功能有积极预测作用 五年后的轨迹，以及ii)中等强度PA的变化将伴随着变化 在五年的时间里，在大脑的葡萄糖代谢和认知方面。这项研究可能具有重要的意义 通过揭示PA通过抑制基础病理生理学的机制来影响翻译 AD，结果，延迟了症状的出现。该项目得到了世界银行的广泛资源支持 威斯康星州阿尔茨海默病研究中心。

PROJECT SUMMARY / ABSTRACT Currently, there are over 5.7 million Americans living with Alzheimer’s disease (AD). Its prevalence and associated costs are projected to triple in coming decades given the aging of the nation’s population. Because of this looming epidemic, delaying the onset of AD symptoms and curbing the progression of the underlying disease process has become a national public health imperative. Delaying symptom onset by as little as five years could reduce the prevalence of AD by half. Unfortunately, currently-available drug treatments for AD are not curative. The urgency of alternative approaches for halting the crisis posed by AD cannot be overstated. There is increasing recognition for the link between physical activity (PA) and prevention of AD. Meta-analytic data of prospective studies have demonstrated that those who are physically active during midlife are at a 35% decreased risk for cognitive decline, and 45% reduced risk for AD in later life. Whereas the beneficial effects of PA on risk for AD have been well studied, investigations of the influence of PA on biomarkers of AD pathology are just beginning. The emerging evidence from our published work and that of other groups suggests that PA is positively associated with many indices of brain health, including cerebral glucose metabolism. Even so, there remain critical gaps in our knowledge. First, the majority of studies have relied of self-report measures of PA which are prone to reporting biases. Second, extant studies have been cross-sectional in nature, and therefore, we currently do not know how baseline levels of PA influence the trajectory of AD biomarkers prospectively. Equally important, we do not know the extent to which changes in PA over time track with changes in AD biomarkers. Therefore, the objective of this proposal is to determine the longitudinal relationship between PA, cerebral glucose metabolism and cognitive function in 50 adults at-risk for AD. We originally studied these individuals in 2013 and now propose to bring them back for a 5-year follow up. Our Central Hypothesis is that longitudinal trajectories of cerebral glucose metabolism and cognition will vary as a function of moderate-intensity PA. We will test our hypothesis with two specific aims: Aim 1: Investigate the longitudinal relationship between PA and cerebral glucose metabolism and Aim 2: Investigate the longitudinal relationship between PA and cognitive function. We predict i) that engagement in moderate-intensity PA performed at baseline (5 years prior) will positively predict longitudinal cerebral glucose metabolism and cognitive trajectories five years later, and ii) changes in moderate-intensity PA will concomitantly associate with changes in cerebral glucose metabolism and cognition over a five year period. This research could have significant translational impact by uncovering a mechanism through which PA curbs the underlining pathophysiology of AD and as a result, delays symptom onset. The project is supported by the extensive resources of the Wisconsin Alzheimer’s Disease Research Center.