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: 9277339
• 负责人: Thomas O Obisesan
• 金额: $ 55.24万
• 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/9277339
• 关键词: Adverse effects; Aerobic Exercise; Affect; African American; Aging; Alzheimer' s Disease; Amyloid; Apolipoprotein E; Attenuated; Biological Markers; Biological Preservation; Brain; Cardiovascular Diseases; Cerebral Hypoxia; 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 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; Neuropsychology; Outcome Measure; Outcome Study; Oxygen saturation measurement; Participant; Performance; Persons; Pharmacotherapy; Pilot Projects; Population; Prevention strategy; Principal Investigator; Prospective Studies; Public Health; Puncture procedure; Quality of life; Questionnaires; Randomized; Randomized Controlled Trials; Recruitment Activity; Research Infrastructure; Research Personnel; Resources; Risk; Risk Factors; Sample Size; Sampling; Sleep; Spinal Tap; Stretching; Sum; Supervision; Testing; Time; Training; Universities; Wellness Center; Wireless Technology; Work; base; blood glucose regulation; brain volume; cardiovascular disorder risk; cardiovascular health; cerebral oxygenation; cognitive neuroscience; cognitive performance; cognitive process; cognitive task; cognitive testing; community setting; cost; cytokine; design; dexterity; early experience; educationally disadvantaged; evidence base; executive function; exercise intervention; exercise program; exercise regimen; exercise training; experience; fitness; follow-up; functional decline; group intervention; health disparity; improved; interest; intervention effect; mild cognitive impairment; neuroimaging; neuroimaging marker; prevent; prospective; psychologic; public health relevance; screening; symptom treatment; treadmill; 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（由申请人提供）：尽管抗胆碱酯酶疗法极大地改善了阿尔茨海默病（AD）的对症治疗，但尚未证明它们能够显着减缓疾病进展；并且淀粉样蛋白导向疗法产生了令人失望的基于证据的结果。在横断面和前瞻性研究中，相对无副作用的生活方式正在成为药物治疗的替代方案或辅助手段，一些随机对照试验已证明有氧运动训练可以改善老年人的认知能力。然而，人们对这些影响的机制仍知之甚少，因为人们现在认识到心血管疾病 (CVD) 风险会促进 AD 的发展，因此测试生活方式调整是否可以降低 CVD 风险可以有利地改变认知轨迹和标志物至关重要。此类干预措施可能有益于处于 AD 早期和临床可识别前驱阶段的患者，例如轻度认知障碍 (MCI)。值得注意的是，目前在心血管疾病风险较高的非裔美国人 (AA) 中缺乏此类数据。 AD. 大约 10 年来，首席研究员一直在研究健身适应对心血管 (CV) 健康的影响，最近，他获得了 2 年的资助，以研究每周 3 次、为期 6 个月的有氧运动的影响。这项正在进行的研究使首席研究员能够展示在主要 AA 样本中招募、注册、测试、收集和管理相关神经影像试点数据的能力，而这种实验室方法的运动干预研究是可行的。需要证明因果关系，这样的设计可能不适合现实生活中的应用，并且对许多经济和教育上处于不利地位的老年 AA 提出了要求，这些老年人经历了认知退化的早期症状。为了从逻辑上扩展这项正在进行的工作，他寻求启动一项为期 18 个月的研究，在更理想的社区环境中测试运动适应对记忆的影响的现实生活适用性，收集基线、3 个月、6 个月、9 个月、12 个月和 18 个月的结果测量将提供试点。因此，这项试点研究的目的是检验一项为期 18 个月的社区研究的可行性。 6 个月的主动干预和 12 个月的被动随访）有氧运动训练对 AA MCI 受试者神经退行性疾病的影响 我们将通过将受试者随机分为 2 组之一来检验我们的假设：1.）有氧运动； 2.）伸展运动（对照）。我们提出，有氧运动组在认知测量方面表现优于对照组。其次，我们将确定训练引起的认知变化是否与脑容量的增加有关。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、脑氧合和缺氧诱导因子（HIF-1α）基因表达的干预效果，以及载脂蛋白 E 基因 (APOE)，旨在评估其对训练引起的认知变化的调节作用，由神经影像学、神经学、认知神经科学和运动生理学领域经验丰富的研究人员组成的团队已与哥伦比亚特区合作开展这项研究。老龄事务办公室（DCOA）、DCOA 运营的第 6 区老年健康中心主任以及老龄事务牵头机构（DCOA 支持的社区基层组织），我们将招募、登记、随机化和培训参与者在获得知情同意并完成初步评估后，参与者将接受初步运动筛查，以确定他们安全运动的能力，然后将 80 名志愿者随机分为有氧运动 (40) 和对照组 (40)；将获得神经影像和生物标志物测量结果。两组将在健康中心接受 3 次/周的有氧运动组干预，为期 6 个月。一个 规定但自由生活 40 分钟、每周 3 次的锻炼方案，而对照组将在 3 个月、6 个月后（积极干预期）以及 9、12 和 18 个月时重复进行基线测试；跑步机、腰椎穿刺 (LP) 和脑磁共振成像 (MRI) 测试仅在基线和 6 个月时进行，比较组间认知表现、生物标志物和神经影像测量的变化。虽然我们仍然认识到其他计划中或正在进行的健身和记忆试验，但拟议的研究是独特的，因为：它是我们正在进行的工作的逻辑延伸；在主要是 AA 的样本中测试了所提出的假设。的数据仍然存在，因此将促进健康差异的缩小；将获得多个时间点（基线、3、6、9、12 和 8 个月）的数据，从而可以评估持续时间和剂量的影响干涉结果测量；测试所提出的干预措施在社区环境中的现实适用性；并生成有关这些干预措施影响记忆的机制的试点数据。风险最大的人群，并且可以预防或减轻与 AA 痴呆症相关的身体、心理和经济负担。