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

描述（由申请人提供）：确定老年人步态和跌倒的因果关系和可改变的机制对于风险评估和早期干预至关重要。在此，我们提出了一种结合临床神经心理学、认知神经科学和遗传学的三层次理论驱动方法来探索70岁及以上居住在社区的非痴呆受试者的步态和跌倒机制。我们发现临床神经心理学测量的注意力和执行功能在横截面上与步态和跌倒密切相关。在此，我们建议前瞻性地研究捕获注意力、执行功能、言语智商和记忆领域的特定临床神经心理学测试如何预测居住在社区的大量老年人的步态表现（目标1假设a）和跌倒（目标2假设a）。我们进一步提出了一种补充神经科学方法，使用注意网络测试（ANT）来检验经验定义的注意组成部分（警觉、定向、执行注意）如何与步态（目标1假设b）和跌倒（目标2假设b）相关。这些注意力的子组成部分与单独的大脑网络有关，因此可以推进研究，以确定与步态和跌倒相关的机制。在多巴胺能基因中，儿茶酚o -甲基转移酶（COMT）与注意力和执行功能的关系最为一致。鉴于COMT与执行控制之间的联系，这与步态受损和跌倒有关，可能会发现衰老过程中人类运动认知控制的一种新的遗传联系。在此，我们将研究COMT多态性是否与步态（目标1假设c）和跌倒（目标2假设c）直接或通过认知控制相关。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方案，以应对老年人步态和跌倒的下降。意义：确定步态障碍和跌倒的原因和可改变的因素是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为风险评估提供有价值的见解，以及为有步态和跌倒风险的个体提供康复和药理学干预。

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.