Genes, Exercise, Neurocognitive and Neurodegeneration: Community-Based Approach

基因、运动、神经认知和神经退行性疾病：基于社区的方法

• 批准号: 8644082
• 负责人: Thomas O Obisesan
• 金额: $ 55.5万
• 依托单位: HOWARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-15 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8644082
• 关键词: Adverse effects; Aerobic; Aerobic Exercise; Affect; African American; Aging; Alzheimer' s Disease; Amyloid; Apolipoprotein E; Attenuated; Biological Markers; Biological Preservation; Boxing; Brain; Cardiovascular Diseases; Cardiovascular system; Cerebrospinal Fluid; Cerebrum; Cholinesterase Inhibitors; Clinical; Clinical dementia rating scale; Cognition; Cognitive; Collection; Communities; Consent; Control Groups; Data; Dementia; Deterioration; Development; Disease Progression; District of Columbia; Dose; Economic Burden; Economically Deprived Population; Elderly; Emotional; Enrollment; Etiology; Exercise; Exercise Physiology; Funding; Gene Expression; Genes; Geriatrics; Goals; Health; Health Care Costs; Hypoxia Inducible Factor; Impaired cognition; Inflammatory; Informed Consent; Intervention; Intervention Studies; Laboratories; Lead; Life; Life Style; Lipids; Magnetic Resonance Imaging; Measurement; Measures; Mediation; Memory; Methods; Morbidity - disease rate; Nerve Degeneration; Neurobehavioral Manifestations; Neurocognitive; Neurology; Outcome Measure; Outcome Study; Oxygen saturation measurement; Participant; Performance; Persons; Pharmacotherapy; Pilot Projects; Population; Prevention strategy; Principal Investigator; Process; Prospective Studies; Public Health; Puncture procedure; Quality of life; Questionnaires; Randomized; Randomized Controlled Trials; Recruitment Activity; Regimen; Research Infrastructure; Research Personnel; Resources; Risk; Risk Factors; Sample Size; Sampling; Sleep; Spinal Tap; Staging; Stretching; Sum; Testing; Time; Training; Universities; Wellness Center; Wireless Technology; Work; base; blood glucose regulation; brain volume; cardiovascular disorder risk; cognitive neuroscience; community setting; cost; cytokine; design; early experience; educationally disadvantaged; evidence base; executive function; experience; fitness; follow-up; functional decline; group intervention; health disparity; improved; interest; intervention effect; mild cognitive impairment; neuroimaging; neuropsychological; prevent; programs; prospective; psychologic; screening; treatment as usual; trend; volunteer; ward

DESCRIPTION (provided by applicant): Although anticholinesterase therapies have greatly improved the symptomatic treatment of Alzheimer's disease (AD), they have not been demonstrated to significantly slow the disease progression; and amyloid- directed therapies have produced disappointing results. A promising evidence-based and relatively side-effect free lifestyle approach is emerging as an alternative or adjunct to drug therapy. In cross-section and prospective studies, and a few randomized controlled trials; aerobic exercise-training has been demonstrated to improve cognition in older subjects. However, the mechanisms of these effects remain poorly understood. Because it is now recognized that cardiovascular disease (CVD) risks can catalyze AD development, it is vital to test whether lifestyle adaptation shown to reduce CVD risks can favorably modify cognitive trajectories and markers of neurodegeneration. Such interventions may benefit those at an early and clinically discernible prodromal stage of AD such as mild cognitive impairment (MCI). Notably, such data are currently lacking in African Americans (AA)s who harbor higher rate of CVD risks and AD. For ~10 years, the Principal Investigator has conducted studies on the effects of fitness adaptation on cardiovascular (CV) health. Recently, he received 2 years of funding to examine the effects of 3-times/week 6-month aerobic exercise-training on cognition in the laboratory setting. This ongoing study has allowed the Principal Investigator to demonstrate the ability to recruit, enroll, test, collect and manage related neuroimaging pilot data in a predominantly AA sample. While such a laboratory approach to exercise intervention study is required to prove causation, such a design may not lend itself to real-life application, and is demanding for many economically and educationally disadvantaged older AAs experiencing early symptoms of cognitive deterioration. To logically extend this ongoing work, he seeks to initiate an 18-month study, testing real-life applicability o the effects of exercise adaptation on memory in a more ideal community setting. Collection of outcome measures at baseline, 3- month, 6-month, 9-month, 12-month and 18-month will provide pilot data to inform dose and duration effects of exercise on outcome measures. In addition to augmenting enrollments, the proposed approach will bolster retention. The objectives of this pilot study, therefore, are to examine the feasibility of a community-based 18-month study (6-month active intervention and 12-month passive follow-up) aerobic exercise-training on neurodegeneration in AAs MCI subjects. We will test our hypotheses by randomizing subjects into one of 2 groups: 1.) aerobic-exercise; and 2.) stretch-exercise (control). We proposed that the aerobic-exercise group will perform better than control group on cognitive measures. Secondarily, we will determine whether training- induced changes in cognition relate to increases in brain volume. Explanatorily, we will also investigate intervention effects on cerebrospinal fluid (CSF) biomarkers, selected CVD risk factors and biomarkers, cerebral oxygenation and Hypoxia-Inducible Factors (HIF-1α) gene expression, and Apolipoprotein E gene (APOE), to assess their mediation of training-induced changes in cognition. A team of experienced investigators in neuroimaging, neurology, cognitive neuroscience, and exercise physiology has been assembled to conduct this study. Working collaboratively with the District of Columbia Office on Aging (DCOA), the Directors of the Ward 6 Senior Wellness Center operated by DCOA, and the lead agencies on aging (community grassroots organizations supported by DCOA), we will recruit, enroll, randomize, and train participants at the wellness center. After obtaining informed consent and completing an initial assessment, participants will undergo initial exercise screening to determine their ability to exercise safely. Following randomization of 80 volunteers into aerobic-exercise (40) and control (40); baseline neuropsychological, neuroimaging and biomarker measurements will be obtained. Both groups will undergo 3 times/week supervised group-specific intervention at the wellness center for 6 months. After the initial 6 months of active intervention, the aerobic-exercise group will follow a prescribed but free living 40 minutes, 3 time/week exercise regimen, while the control group returns to usual care. Baseline tests will be repeated at 3 month, after 6 months (active intervention period); and at 9, 12 and 18 months (passive follow-up period). Treadmill, lumber puncture (LP) and brain magnetic resonance imaging (MRI) tests will occur only at baseline and 6 months. Between groups changes in cognitive performance, biomarkers, and neuroimaging measurements will be compared using appropriate multivariate methods. While we remain cognizant of other planned or ongoing fitness and memory trial, the proposed study is unique in the sense that: it is a logical extension of our ongoing work; tests the proposed hypotheses in predominantly AA sample in whom paucity of data remains, and therefore, will advance reduction in health disparity; will obtain data at multiple time-points (baseline, 3, 6, 9, 12 and 8 months) and therefore allow for the assessments of the effects of duration and dose of intervention on outcome measures; test the real-life applicability of the proposed intervention in a community setting; and generate pilot data on the mechanisms by which these interventions affects memory. Importantly, outcomes from this study may lead to practical and effective strategy to delay cognitive decline in populations at most risk, and can prevent or attenuate the physical, psychological and the economic burden associated with dementia in AAs.

描述（由适用提供）：尽管抗胆碱酯酶疗法已大大改善了阿尔茨海默氏病（AD）的症状治疗，但尚未证明它们会显着减慢疾病进展。淀粉样蛋白导向的疗法产生了令人失望的结果。有希望的基于证据和相对副作用的自由生活方式方法正在成为药物治疗的替代方案或辅助手段。在横断面和前瞻性研究中，以及一些随机对照试验；有氧运动训练已被证明可以改善神经退行性的认知轨迹和标记。但是，这些作用的机制仍然很少理解。因为现在已经认识到心血管疾病（CVD）的风险可以催化AD发育，因此测试生活方式适应是否已被证明可以降低CVD风险通常可以改变神经退行性的认知轨迹和标志物。这种干预措施可能会在AD的早期和临床上可见的前驱阶段受益于轻度认知障碍（MCI）。值得注意的是，目前缺乏此类数据的非洲裔美国人（AA），具有更高的CVD风险和AD的数据。大约10年来，首席研究人员一直对适应性适应对心血管（CV）健康的影响进行研究。最近，他获得了2年的资金，以研究3次/周6个月的有氧运动训练对实验室认知的影响。这项正在进行的研究使主要研究者能够证明在主要AA样本中招募，注册，测试，收集和管理相关的神经成像数据。尽管需要采用这种实验室干预研究来证明原因，但这种设计可能不适合现实生活，并且要求许多经济和教育上受到教育的年龄较大的AA，以表现出认知能力的早期症状。从逻辑上讲，他试图启动一项18个月的研究，测试现实生活中的适用性o锻炼适应在更理想的社区环境中对记忆的影响。在基线，3个月，6个月，9个月，12个月和18个月的基线时收集结果度量，将提供试验数据，以告知运动对锻炼对成果指标的剂量和持续时间。除了增加入学率外，拟议的方法还将支持保留。因此，这项试验研究的目标是检查基于社区的18个月研究（6个月的活跃干预和12个月的被动随访）对AAS MCI受试者神经变性的有氧运动训练。我们将通过将受试者随机分为两个组之一来检验我们的假设：1。）有氧运动；和2.）拉伸运动（控制）。我们提出，在认知测量方面，有氧运动组的表现将比对照组更好。次要，我们将确定训练引起的认知变化是否与大脑体积增加有关。解释说，我们还将研究对脑脊液（CSF）生物标志物，选定的CVD危险因素和生物标志物，脑氧合和低氧诱导因子（HIF-1α）基因表达（HIF-1α）基因表达以及载脂蛋白E基因（APOE）的影响。一组经验丰富的研究人员在神经影像学，神经病学，认知神经科学和运动生理学方面进行了组装，以进行这项研究。与DCOA经营的Ward 6高级健康中心董事以及老龄化机构（由DCOA支持的社区基层组织）与哥伦比亚特区的老化办公室（DCOA）合作，我们将在健康中心招募，招募，随机和培训参与者。在获得知情同意并完成初步评估后，参与者将进行初步锻炼筛查，以确定他们的安全运动能力。在将80名志愿者随机化进行有氧运动（40）和对照（40）之后；将获得基线神经心理学，神经影像学和生物标志物测量。两组将在健康中心进行3次/周监督小组特定的干预措施6个月。在有效干预的最初6个月后，有氧运动组将遵循 处方但免费的生活40分钟，3个时间/周的运动方案，而对照组则返回通常的护理。基线测试将在6个月后3个月重复（主动干预期）；并在9、12和18个月（被动随访期）。跑步机，木材穿刺（LP）和脑磁共振成像（MRI）测试仅在基线和6个月时进行。两组之间，将使用适当的多元方法比较认知性能，生物标志物和神经影像学测量的变化。尽管我们仍然意识到其他计划或正在进行的健身和记忆试验，但拟议的研究在某种意义上是独一无二的：这是我们正在进行的工作的逻辑扩展；测试主要是AA样本中的拟议假设，其中数据仍然存在，因此将提高健康差异的降低；将在多个时间点（基线，3、6、9、12和8个月）获得数据，因此可以评估干预持续时间和剂量对结果指标的影响；在社区环境中测试拟议干预措施的现实生活；并生成有关这些干预措施影响记忆的机制的试验数据。重要的是，这项研究的结果可能会导致实用有效的战略，以延迟人口的认知能力下降，并可以预防或衰减AAS中与痴呆症相关的身体，心理和经济伯恩。