A Brain-based Approach to Enhancing Executive Control Functions in Healthy Aging

描述（由申请人提供）：目标方向不明确，或在分散注意力的环境中失去集中注意力和“专注于任务”的能力，是老年人的常见抱怨。这种主观报告与认知衰老研究文献中出现的共识一致，即维持目标方向所必需的执行控制过程特别容易随着年龄的增长而下降。不幸的是，尽管执行控制缺陷对日常生活功能和晚年功能独立性的维持有重大影响，但文献中报道的有效治疗方法很少。在这里，我们认为，由于我们对大脑中执行控制处理的神经机制的理解不足，这些治疗的效果受到了阻碍。该提案的第一个目标是开发执行控制过程的强大生物标志物，以补充治疗效果的神经认知和功能结果测量。这些生物标志物将用于识别对治疗反应最灵敏的神经过程，并预测神经认知和功能增益，从而为设计更有针对性和更有效的基于大脑的治疗提供信息。本研究的第二个目的是利用基于策略和有针对性的过程训练方案来明确测试这种基于大脑的方法，以增强健康老年人的执行控制处理。通过这种综合治疗方法，我们打算通过在治疗师指导的、基于策略的目标管理计划中加强和情境化目标培训来利用从目标培训中获得的收益。这个程序是标准化的过程的兴趣（执行控制），但指导策略应用到个人突出的，自我产生的目标和个人相关的现实生活中的情况。结果将在神经、神经认知和功能结果水平上进行评估。这种从大脑到行为再到持久功能改变的脚手架式方法，确保认知补救工作直接惠及老年人，更广泛地惠及社会，因为它推迟了对家庭护理、养老院或医院服务的需求，同时保持了老年人的功能独立性和尊严。

DESCRIPTION (provided by applicant): Poor goal direction, or loss of ability to concentrate and 'stay on task' in a distracting environment, is a common complaint in advanced age. Such subjective reports are consistent with an emerging consensus in the cognitive aging research literature suggesting that the executive control processes necessary for maintaining goal direction are particularly susceptible to decline with advancing age. Unfortunately, there have been few efficacious treatments for executive control deficits reported in the literature despite their significant impact on daily life functions and the maintenance of functional independence into later life. Here we argue that the efficacy of such treatments is hindered by our poor understanding of the neural mechanisms subserving executive control processing in the brain. The first aim of the proposal is to develop robust biomarkers of executive control processes to complement neurocognitive and functional outcome measures of treatment efficacy. These biomarkers will serve to identify neural processes that are most responsive to treatment and predictive of neurocognitive and functional gain, thus informing the design of more targeted and efficacious brain-based treatments. A second aim of the proposal is to test this brain-based approach explicitly using an integrated strategy-based and targeted process training protocol to enhance executive control processing in healthy aging. Through this combined treatment approach we intend to leverage gains realized from targeted training by reinforcing and contextualizing them in a therapist-guided, strategy-based goal management program. This program is standardized for the process of interest (executive control), but guides strategy application to individually-salient, self-generated goals and personally-relevant real-life situations. Outcomes will be assessed at the neural, neurocognitive and functional outcome levels. Such a scaffolded approach, building from the level of brain to behavior to lasting functional change, ensures that cognitive remediation efforts benefit older adults directly, and society more generally, by delaying the need for home care, nursing home or hospital services while preserving the functional independence and dignity of an aging population. PUBLIC HEALTH RELEVANCE: Cognitive decline associated with normal aging can have a broad impact on an individual's productivity, physical health and general sense of well-being. Especially with the expected increase in the aging population in the next few decades, age-related cognitive decline is a major public health issue. The aim of this project is to investigate the neural mechanisms underlying age-related cognitive decline and to develop interventions and biomarkers to evaluate the efficacy of these interventions.