Augmenting Cognitive Training in Older Adults - The ACT Grant

摘要： 这项随机临床试验将测试额叶皮质的经颅直流电刺激(Tdcs)是否增强。 与年龄相关的老年人接受认知训练后获得的神经认知和功能结果 认知能力下降。经过充分验证的神经认知功能和日常能力测量的变化将起到 结果衡量标准。神经可塑性和学习的功能和结构神经成像生物标记物(fMRI、GABA 夫人等)将测量受认知老化影响的特定大脑区域与干预相关的变化。Tdcs 是一种促进神经可塑性和学习的非侵入性脑刺激方法。因此，当用作 辅助性干预，可增强认知训练效果。这项研究将利用现有的多点临床 麦克奈特大脑研究所的试验基础设施位于老年人人数最多的两个州 在美国：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 代表着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 对公共卫生的关注。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，有效期长达10年。然而，效果通常仅限于训练的任务，几乎没有 转移到其他认知能力或日常技能上。阿尔茨海默氏症患者的影响也可能会降低 疾病风险因素。一项两阶段多点随机临床试验将检查个体和联合影响 认知训练与经颅直流电刺激(Tdcs)在与年龄相关的老年人中的配对 认知功能减退(n=360；每个站点120个)。参加者将由65-90岁的老年男性和女性组成 与年龄相关的认知能力下降的证据，但不是轻度认知障碍或阿尔茨海默病(≥25)。我们将比较变化 在认知和脑功能方面，CT和CT结合TDC使用全面的神经认知， 对大脑结构、功能和代谢状态的临床和多模式神经成像评估。功能性 磁共振成像(FMRI)将被用来评估大脑在工作记忆、注意力和 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记物。我们假设：1)tdcs 将增强神经认知功能、脑功能和CT的功能结果；2)tDCs对CT将 在训练后维持12个月，以及3)脑代谢、神经功能的神经成像生物标记物 静息与主动认知任务的可塑性(GABA浓度)和脑功能反应(FMRI)将 使用某些阿尔茨海默氏症危险因素(例如，APOE4基因，家族病史)预测个体对tDCs的反应 阿尔茨海默病)预示较差的认知和功能结果。到目前为止，还没有研究表明 综合研究CT和TDCS联合干预在老年人群中的应用。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结合认知训练对抗认知衰退的价值。

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.