Predictors of Gait and Falls in Aging: Linking Cognitive Control to Genes

描述（由申请人提供）： 确定老年人步态和福尔斯跌倒的因果和可改变机制对于风险评估和早期干预至关重要。在此，我们提出了一个三个层次的理论驱动的方法，结合临床神经心理学，认知神经科学和遗传学，探讨步态和福尔斯在非痴呆的受试者年龄70岁及以上的社区居住的机制。我们发现，临床神经心理学措施的注意力和执行功能密切相关的步态和福尔斯在横截面。在此，我们建议前瞻性地研究如何捕捉领域的注意力执行功能，言语智商和记忆力的具体临床神经心理学测试预测步态表现（目标1假设a）和福尔斯（目标2假设a）在一个大型队列的老年人居住在社区。我们进一步提出了一个补充的神经科学方法，使用注意力网络测试（ANT），以检查经验定义的注意力（警觉，定向，执行注意力）的组成部分是如何与步态（目标1假设B）和福尔斯（目标2假设B）。注意力的这些子成分与单独的大脑网络相关，因此可以推进研究，以识别与步态和福尔斯相关的机制。在多巴胺能基因中，儿茶酚O-甲基转移酶（COMT）一直与注意力和执行功能相关。鉴于COMT和执行控制之间的关联，这与步态受损和福尔斯有关，可以确定衰老中人类运动的认知控制的新遗传联系。在此，我们将研究COMT多态性是否直接或通过认知控制与步态（目标1假设c）和福尔斯（目标2假设c）相关。我们的长期目标是确定特定的认知和遗传机制，以制定更有效的风险评估和干预计划，在老年人的步态和福尔斯下降。重要性：确定步态障碍和福尔斯的因果和可改变因素，作为制定更有效的评估和干预措施的前奏，对公共卫生至关重要。我们相信，这一理论驱动的应用将提供有价值的见解，风险评估，以及康复和药物干预的个人在步态和福尔斯下降的风险。

DESCRIPTION (provided by applicant): Identifying causal and modifiable mechanisms of gait and falls in older adults is crucial for risk assessment and early interventions. Herein, we propose a three-level theory-driven approach integrating Clinical Neuropsychology, Cognitive Neurosciences, and Genetics to explore mechanisms of gait and falls in non- demented subjects age 70 and older residing in the community. We showed that clinical neuropsychological measures of attention and executive function were strongly related to gait and falls at cross-section. Herein, we propose to examine prospectively how specific clinical neuropsychological tests capturing the domains of Attention Executive function, Verbal IQ and Memory predict gait performance (aim 1 hypothesis a) and falls (aim 2 hypothesis a) in a large cohort of older adults residing in the community. We further propose a complementary neuroscience approach using the Attention Networks Test (ANT) to examine how empirically defined components of attention (alerting, orienting, executive attention) are related to gait (aim 1 hypothesis b) and falls (aim 2 hypothesis b). These sub-components of attention have been related to separate brain networks and thus can advance research toward identifying mechanism as opposed to correlates of gait and falls. Among the Dopaminergic genes, Catechol O-methyltransferase (COMT) has been most consistently related to attention and executive functions. In light of the association between COMT and executive control, which has been implicated in impaired gait and falls, a novel genetic link of cognitive control of human locomotion in aging may be identified. Herein, we will examine whether COMT polymorphisms are related directly or via cognitive control to gait (aim 1 hypothesis c) and falls (aim 2 hypothesis c). Our long-term goal is to identify specific cognitive and genetic mechanisms pertinent to developing more efficient risk assessment and intervention programs of decline in gait and falls in older adults. Significance: It is of vital public health importance to identify causal and modifiable factors of gait impairment and falls as a prelude towards formulating more effective assessments and interventions. We believe that this theory driven application will provide valuable insights into risk assessment, as well as rehabilitative and pharmacological interventions for individuals at risk of decline in gait and falls.