Augmenting Cognitive Training in Older Adults - The ACT Grant

摘要： 这项随机临床试验将测试经颅直流电刺激（tDCS）额叶皮质是否能增强 认知训练对经历年龄相关疾病的老年人的神经认知和功能结果 认知能力下降神经认知功能和日常能力的有效指标的变化将作为 结果测量。神经可塑性和学习的功能和结构神经影像学生物标志物（fMRI，GABA MRS等）将测量受认知老化影响的特定大脑区域的干预相关变化。tDCS 是一种非侵入性的脑刺激方法，促进神经可塑性和学习。因此，当用作 tDCS的持续干预可增强认知训练的效果。本研究将利用现有的多中心临床 McKnight Brain Institutes的试验基础设施位于老年人最多的两个州 美国：佛罗里达大学、迈阿密大学和亚利桑那大学。65岁以上的成年人 是美国人口中增长最快的群体。因此，与年龄相关的认知能力下降是一个主要的 关注公众健康。最近的研究表明，老年人的认知训练可以改善认知能力， 性能，效果持续长达10年。然而，效果通常仅限于训练的任务， 转移到其他认知能力或日常技能上。在阿尔茨海默氏症患者中， 疾病风险因素。一项两阶段的多中心随机临床试验将检查个体和联合影响 将认知训练与经颅直流电刺激（tDCS）相结合， 认知能力下降（n = 360;每个研究中心120例）。参加者将包括65-90岁的老年男女， 年龄相关的认知能力下降，但不是MCI或阿尔茨海默病（莫卡≥25）。我们将比较变化 在认知和脑功能导致的CT和CT结合tDCS使用一个全面的神经认知， 临床和多模式神经影像学评估脑结构、功能和代谢状态。功能 磁共振成像（fMRI）将被用来评估大脑在工作记忆，注意力， 记忆编码; CT训练的主动认知能力。质子磁共振波谱（MRS）将 评估神经可塑性、GABA浓度和大脑代谢的标志物。我们假设：1）tDCS 将增强神经认知功能、脑功能和CT的功能结局; 2）tDCS对CT的影响将 在训练后维持长达12个月，以及3）脑代谢、神经系统代谢和神经系统代谢的神经成像生物标志物。 可塑性（GABA浓度）和功能性脑反应（fMRI）在休息与主动认知任务将 预测个体对tDCS的反应，具有某些阿尔茨海默病风险因素（例如，APOE 4基因型，家族史 阿尔茨海默病）预测较差的认知和功能结果。到目前为止，没有任何研究 综合检查老年人的CT和tDCS联合干预。这项研究将提供明确的见解 在快速老龄化的美国人口中使用tDCS与认知训练对抗认知下降的价值。

ABSTRACT: This randomized clinical trial will test whether transcranial direct current stimulation (tDCS) of frontal cortices enhances neurocognitive and functional outcomes achieved from cognitive training in older adults experiencing age-related cognitive decline. Change in well-validated measures of neurocognitive function and everyday abilities will serve as outcome measures. Functional and structural neuroimaging biomarkers of neural plasticity and learning (fMRI, GABA MRS, etc.) will measure intervention-associated alterations in specific brain regions impacted by cognitive aging. tDCS is a noninvasive brain stimulation method that facilitates neural plasticity and learning. Accordingly, when used as an adjunctive intervention, tDCS may augment cognitive training effects. This study will leverage existing multisite clinical trial infrastructure at McKnight Brain Institutes located in two of the states with the largest representation of older adults in the United States: University of Florida, University of Miami, and University of Arizona. Adults over the age of 65 represent the fastest growing group in the US population. As such, age-related cognitive decline represents a major concern for public health. Recent research suggests that cognitive training in older adults can improve cognitive performance, with effects lasting up to 10 years. However, effects are typically limited to the tasks trained, with little transfer to other cognitive abilities or everyday skills. Effects may also be reduced in people with Alzheimer's disease risk factors. A two-phase multisite randomized clinical trial will examine the individual and combined impact of pairing cognitive training with transcranial direct current stimulation (tDCS) in older adults experiencing age-related cognitive decline (n = 360; 120 per site). Participants will consist of elderly men and women 65-90 years of age with evidence of age-related cognitive decline, but not MCI or Alzheimer's disease (MoCA≥25). We will compare changes in cognitive and brain function resulting from CT and CT combined with tDCS using a comprehensive neurocognitive, clinical, and multimodal neuroimaging assessment of brain structure, function, and metabolic state. Functional magnetic resonance imaging (fMRI) will be used to assess brain response during working memory, attention, and memory encoding; the active cognitive abilities trained by CT. Proton magnetic resonance spectroscopy (MRS) will assess markers of neural plasticity, GABA concentrations, and cerebral metabolism. We hypothesize that: 1) tDCS will enhance neurocognitive function, brain function, and functional outcomes from CT; 2) Effects of tDCS on CT will be maintained up to 12 months following training, and 3) Neuroimaging biomarkers of cerebral metabolism, neural plasticity (GABA concentrations) and functional brain response (fMRI) during resting vs. active cognitive tasks will predict individual response to tDCS, with certain Alzheimer's risk factors (e.g., APOE4 genotype, family history of Alzheimer's disease) predicting poorer cognitive and functional outcome. To date, no studies have comprehensively examined combined CT and tDCS intervention in the elderly. This study will provide definitive insight into the value of combating cognitive decline in a rapidly aging US population using tDCS with cognitive training.