Neural Effects of Exercise, Cognitive, or Combined Training in AD At-Risk Elders

运动、认知或联合训练对 AD 高危老年人的神经影响

• 批准号: 7816542
• 负责人: STEPHEN MARK RAO
• 金额: $ 49.98万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7816542
• 关键词: Activities of Daily Living; Address; Adverse effects; Aerobic Exercise; Age; Aging-Related Process; Alleles; Alzheimer' s Disease; Alzheimer' s disease risk; Apolipoprotein E; Applications Grants; Area; Attention; Biological Markers; Brain; Clinical; Clinical Trials; Cognitive; Combined Modality Therapy; Control Groups; Data; Diagnosis; Disease; Educational Intervention; Elderly; Epidemiology; Episodic memory; Exercise; Exercise stress test; Exhibits; Family history of; Family member; Financial compensation; Functional Magnetic Resonance Imaging; Future; Goals; Grant; Impaired cognition; Individual; Intervention; Intervention Trial; Knowledge; Literature; Longevity; Mass Media; Mediating; Memory; Neurodegenerative Disorders; Neuropsychological Tests; Nursing Homes; Outcome Measure; Participant; Patient Self-Report; Performance; Persons; Population; Population Intervention; Proliferating; Publishing; Quality of life; Randomized Clinical Trials; Randomized Controlled Clinical Trials; Relative (related person); Research; Risk; Semantic memory; Semantics; Staging; Subgroup; Syndrome; Training; Treatment Efficacy; United States; Upper arm; Work; active control; aging population; base; cognitive change; cognitive function; cognitive training; comparative; comparative effectiveness; comparative efficacy; cost; effective intervention; effectiveness research; experience; fitness; flexibility; functional decline; health care delivery; improved; indexing; mortality; neuroimaging; neuropathology; normal aging; post intervention; pre-clinical; primary outcome; public health relevance; relating to nervous system; response; secondary outcome; sedentary; therapy design

DESCRIPTION (provided by applicant): This ARRA Challenge Grant application addresses Broad Challenge Area (05) - Comparative Effectiveness Research and Specific Challenge Topic 05-AG-105 - Comparative Intervention Trials for Diseases and Syndromes of Aging Including Neurodegenerative Diseases. Cognitive decline in older age is associated with loss of independence, functional decline in activities of daily living, nursing home placement, and mortality. Whether cognitive declines occur universally as part of the normal aging process or are the result of subclinical disease activity in a subgroup of elders at-risk for developing Alzheimer's disease (AD) is a matter of scientific debate. At present, older age, family history (FH) of AD, and the presence of the APOE e4 allele are the best, if imperfect, predictors of future cognitive decline in non-demented individuals. Our preliminary studies indicate that functional MRI (fMRI), using a semantic activation task, differentiates cognitively intact elders at-risk for AD from those not at-risk and can predict future cognitive decline in otherwise healthy older individuals. Published trials have demonstrated positive effects of short-term cognitive training (CT) and aerobic exercise training (ET) interventions on cognitive abilities in healthy elders. Despite these positive results, (1) there exist no published studies directly comparing the efficacy of CT to ET in improving cognitive function, (2) no study examining whether a combined treatment (CT+ET) would be superior to a single intervention (CT or ET alone), (3) neuropsychological testing, the primary outcome measure of intervention trials, does not provide information pertaining to the underlying neural changes that mediate cognitive improvement, and (4) interventions have been aimed at non-specific groups of elders rather than targeting elders at-risk for developing AD. To address these gaps in our knowledge, we propose a single specific aim, namely to conduct a 12-week, four-arm, randomized, controlled, clinical trial to compare the efficacy of CT, ET, and Combined Training (CT+ET) relative to an Active Control (AC), consisting of educational and flexibility training. The primary outcome measure is task-activated fMRI, with secondary outcomes assessed with cognitive, ADL, and fitness assessments. The target intervention population will consist of cognitively intact, but physically inactive, older adults at-risk for developing AD based on a positive FH and APOE e4 status. This project will be the first to (1) compare the relative efficacy of CT, ET, and a combined intervention; (2) use functional neuroimaging to assess intervention efficacy; and (3) intervene in older individuals at risk for developing AD. The long-range goal is to evaluate effective, low-risk, and relatively inexpensive interventions for addressing cognitive decline, with enormous implications for containing costs associated with health-care delivery to the ever increasing aging population of the United States. PUBLIC HEALTH RELEVANCE: Published trials have demonstrated positive effects of short-term cognitive training (CT) and aerobic exercise training (ET) interventions on cognitive abilities in healthy elders. Despite these positive results, we do not know the relative efficacy of CT and ET in improving cognitive function or whether a combined treatment (CT+ET) would be superior to a single intervention. We also do not understand the brain changes that mediate cognitive improvement or whether the treatments would work in healthy elders at-risk for developing Alzheimer's disease (AD). In this 12-week, randomized, clinical trial, we will compare the efficacy of CT, ET, and Combined Training (CT+ET) relative to an Active Control, consisting of educational and flexibility training. The primary outcome measure is task-activated fMRI, with secondary outcomes assessed with cognitive, activities of daily living, and fitness assessments. The target intervention population will consist of cognitively intact, but physically inactive, older adults at-risk for developing AD. The overall goal is to evaluate the efficacy of low-risk and relatively inexpensive interventions for addressing cognitive decline in older age.

描述（由申请人提供）：本ARRA挑战基金申请涉及广泛挑战领域(05)-比较有效性研究和特定挑战主题05- ag -105 -包括神经退行性疾病在内的衰老疾病和综合征的比较干预试验。老年人认知能力下降与独立性丧失、日常生活活动功能下降、养老院安置和死亡率有关。认知能力下降是作为正常衰老过程的一部分普遍发生，还是在有患阿尔茨海默病（AD）风险的老年人亚群中是亚临床疾病活动的结果，这是一个科学争论的问题。目前，年龄、AD家族史（FH）和APOE e4等位基因的存在是预测非痴呆个体未来认知能力下降的最佳指标，如果不完美的话。我们的初步研究表明，功能磁共振成像（fMRI），使用语义激活任务，区分认知完好的老年人阿尔茨海默病风险和非风险，并可以预测其他健康老年人未来的认知衰退。已发表的试验表明，短期认知训练（CT）和有氧运动训练（ET）干预对健康老年人的认知能力有积极影响。尽管有这些积极的结果，(1)没有发表的研究直接比较CT和ET在改善认知功能方面的疗效，(2)没有研究检验联合治疗（CT+ET）是否优于单一干预（CT或ET单独），(3)神经心理学测试，干预试验的主要结果测量，并没有提供有关介导认知改善的潜在神经变化的信息。(4)干预措施针对非特定的老年人群体，而不是针对有患AD风险的老年人。为了解决这些知识上的空白，我们提出了一个单一的具体目标，即进行一项为期12周的四组随机对照临床试验，比较CT、ET和联合训练（CT+ET）相对于主动控制（AC）的疗效，包括教育和灵活性训练。主要结果测量是任务激活的fMRI，次要结果评估是认知、ADL和健康评估。目标干预人群将包括认知完整，但缺乏运动，基于FH和APOE e4阳性状态有患AD风险的老年人。本项目将首次(1)比较CT、ET和联合干预的相对疗效；(2)功能神经影像学评价干预效果；(3)对老年AD高危人群进行干预。长期目标是评估解决认知能力下降的有效、低风险和相对廉价的干预措施，这些干预措施对控制向美国日益增长的老龄化人口提供保健服务的相关成本具有巨大影响。