Augmenting Cognitive Training in Older Adults - The ACT Grant

增强老年人的认知训练 - ACT 补助金

• 批准号: 9339496
• 负责人: RONALD A COHEN
• 金额: $ 115.47万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9339496
• 关键词: Adult; Age; Age-Years; Age-associated memory impairment; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Area; Arizona; Arousal; Attention; Blood Vessels; Brain; Brain region; Cerebrum; Characteristics; Choline; Clinical; Clinical Trials; Cognitive; Cognitive aging; Coupled; Demographic Factors; Diabetes Mellitus; Disease; Educational Intervention; Elderly; Elderly man; Elderly woman; Enrollment; Exposure to; Family history of; Florida; Freezing; Functional Magnetic Resonance Imaging; Gender; Genotype; Grant; Growth; Impaired cognition; Individual; Individual Differences; Inferior; Institutes; Intervention; Learning; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Medial; Metabolic; Metabolism; Methods; Motor; Multi-Institutional Clinical Trial; N-acetylaspartate; Nature; Neurocognitive; Neurodegenerative Disorders; Neuronal Plasticity; Outcome; Outcome Measure; Parietal Lobe; Participant; Performance; Phase; Physiological; Placebos; Population; Predictive Value; Prefrontal Cortex; Prevalence; Protons; Public Health; Randomized; Randomized Clinical Trials; Readiness; Recording of previous events; Recruitment Activity; Research; Research Infrastructure; Rest; Risk Factors; Science; Secondary to; Shark; Short-Term Memory; Site; Structure; System; Testing; Time; Training; Training and Education; United States; Universities; active control; age related; association cortex; base; cognitive ability; cognitive enhancement; cognitive function; cognitive performance; cognitive task; cognitive training; combat; effective intervention; experience; follow-up; frontal lobe; functional improvement; functional outcomes; functional status; gamma-Aminobutyric Acid; improved; insight; intervention effect; memory encoding; multi-site trial; multimodality; myoinositol; neuroimaging; neuroimaging marker; power analysis; prevent; processing speed; relating to nervous system; response; skills; white matter

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.

抽象的： 这项随机临床试验将测试额叶皮层增强功能的thrancranial直流电流刺激（TDC） 与年龄相关的老年人认知训练实现的神经认知和功能结果 认知能力下降。改变神经认知功能的验证措施的改变，每天的能力将作为 结果措施。神经塑性和学习的功能性和结构性神经影像学（fMRI，GABA） MRS等）将测量与认知衰老影响的特定大脑区域中与干预相关的变化。 TDCS 是一种无创的脑刺激方法，可促进神经可塑性和学习。彼此说，当用作 辅助干预措施，TDC可能会增加认知训练的效果。这项研究将利用现有的多站点临床 位于两个州的​​McKnight Brain Institutes的试验基础设施，老年人代表最多 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 代表美国人口中增长最快的群体。因此，与年龄相关的认知下降代表了一个主要 关注公共卫生。最近的研究表明，老年人的认知训练可以改善认知 性能，效果长达10年。但是，效果通常仅限于受过训练的任务，很少 转移到其他认知能力或每天技能。阿尔茨海默氏症患者也可能会降低效果 疾病风险因素。两阶段的多站点随机临床试验将检查个体和综合影响 与年龄相关的老年人配对的认知训练与经颅直流刺激（TDC） 认知能力下降（n = 360;每个站点120）。参与者将由65-90岁的男女组成 与年龄相关的认知能力下降的证据，但没有MCI或阿尔茨海默氏病（MOCA≥25）。我们将比较更改 在CT和CT引起的认知和脑功能中，使用全面的神经认知，结合TDC 大脑结构，功能和代谢状态的临床和多模式神经影像学评估。功能 磁共振成像（fMRI）将用于评估工作记忆，注意力和 内存编码；由CT训练的主动认知能力。质子磁共振光谱（MRS）将 评估神经可塑性，GABA浓度和脑代谢的标志。我们假设：1）TDCS 将增强CT的神经认知功能，大脑功能和功能结果； 2）TDC对CT的影响将 训练后长达12个月，以及3）脑代谢的神经影像学生物标志物，神经元 在休息和主动认知任务期间的可塑性（GABA浓度）和功能性脑反应（fMRI）将 预测具有某些阿尔茨海默氏症风险因素的个人反应（例如，APOE4基因型，家族史 阿尔茨海默氏病）预测认知和功能效果较差。迄今为止，没有研究 在较早的情况下，全面检查了CT和TDCS的组合干预。这项研究将提供确定的见解 使用认知训练的TDC在美国迅速老龄化的美国人群中梳理认知能力下降的价值。