Contributions of modifiable physical attributes to cognitive and brain aging

摘要 随着人口老龄化的迅速加速和多次未能找到治疗糖尿病的药物 阿尔茨海默病(AD)，最重要的是确定最易改变的身体特征 可能会减轻老年人的认知和神经衰退。个别研究表明， 活动能力、心肺功能和肌肉力量/力量与老年人的认知能力有关 成年人。然而，由于这些物理属性已被孤立地研究，因此仍不清楚哪种属性 这些属性对于成功的认知老化和大脑维护(保留大脑)是最关键的 年轻)。我们的长期目标是开发一种认知衰老的精确医学模型；也就是，识别 哪些身体属性与特定的认知功能相关联，并实现个性化的定制 锻炼计划，以优化老年人的认知能力。我们当前的总目标是 建议是直接检查活动能力、心肺功能和肌肉的不同贡献。 衡量当前认知能力、大脑健康和纵向认知衰退的力量/力量指标。我们的中央 假设这些物理属性解释了认知上的独特差异，但它们的相对 预测能力在特定的认知域和神经网络中会有所不同。使用金本位 评估活动能力、心肺功能、肌肉力量/力量、认知和大脑结构以及 功能(磁共振成像；MRI)在年轻人、中年人和老年人中，我们将追求 目标如下：1)确定身体属性对认知的贡献，并特别强调 老年人的情景记忆和执行功能。2)确定物理因素的贡献 归因于皮质厚度(T1加权MRI)、脑白质微观结构(弥散加权MRI)和 老年人的脑功能(功能核磁共振)。3)确定哪些身体属性可以预测认知 老年人在2.5年期间的下降以及AD的多基因风险评分是否适中 身体特征与认知能力下降之间的联系。我们将检查哪些可修改的物理 属性，包括运动系统的功能方面，可以预测老年人的认知能力下降。 这项提案的结果数据将影响生活方式干预措施的发展，以优化 老年人的认知表现，因为这项研究将提供关键知识来优化未来 旨在缓解与年龄和阿尔茨海默病相关的认知和神经的运动干预研究 拒绝。此外，我们将研究身体属性-大脑-认知关联是否与年龄有关。 目前的提案非常适合国家老龄研究所的使命，正如我们提议的那样 检查可修改的身体属性，以最大限度地提高生活质量和独立功能 (通过维持认知和大脑健康)在死亡之前。

ABSTRACT With the rapid acceleration of the aging population and repeated failures to find a pharmacological cure for Alzheimer’s disease (AD), it is of paramount importance to identify modifiable physical attributes that are most likely to attenuate cognitive and neural decline in older adults. Individual studies have demonstrated that mobility, cardiorespiratory fitness, and muscle strength/power are associated with cognition among older adults. However, because these physical attributes have been studied in isolation, it remains unknown which of these attributes are most critical for successful cognitive aging and brain maintenance (keeping the brain young). Our long-term goal is to develop a precision medicine model of cognitive aging; that is, to identify which physical attributes are associated with specific cognitive functions and implement individually tailored exercise programs to optimize those cognitive abilities among older adults. Our overall objective in the current proposal is to directly examine differential contributions of mobility, cardiorespiratory fitness, and muscle strength/power metrics to current cognitive abilities, brain health, and longitudinal cognitive decline. Our central hypothesis is that these physical attributes account for unique variance in cognition, but that their relative predictive abilities will differ within specific cognitive domains and neural networks. Using gold-standard assessments of mobility, cardiorespiratory fitness, muscle strength/power, cognition, and brain structure and function (magnetic resonance imaging; MRI) in young, middle-aged, and older adults, we will pursue the following aims: 1) Determine the contribution of physical attributes to cognition, with a specific emphasis on episodic memory and executive function, among older adults. 2) Determine the contribution of physical attributes to cortical thickness (T1-weighted MRI), white matter microstructure (diffusion-weighted MRI) and brain function (functional MRI) among older adults. 3) Identify which physical attributes predict cognitive decline over a 2.5-year period in older adults and whether polygenic risk scores for AD moderate the association between physical attributes and cognitive decline. We will examine which modifiable physical attributes, including functional aspects of the motor system, predict cognitive decline among older adults. Outcome data from this proposal will impact the development of lifestyle interventions for optimization of cognitive performance among older adults, as the study will provide critical knowledge to optimize future exercise intervention studies aimed at mitigating age- and Alzheimer’s disease-related cognitive and neural decline. Moreover, we will examine whether physical attribute-brain-cognition associations are age dependent. The current proposal is well-suited for the mission of the National Institutes of Aging, as we propose to examine modifiable physical attributes that will maximize high quality-of-life years and independent functioning (via maintenance of cognitive and brain health) prior to mortality.