Exploring real-time alterations in cerebral perfusion, BOLD signal, and cognition during physical activity

探索体力活动期间脑灌注、BOLD 信号和认知的实时变化

• 批准号: 9600777
• 负责人: SCOTT M HAYES
• 金额: $ 20.23万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2018-09-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9600777
• 关键词: Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Anterior; Attenuated; Beds; Biological Markers; Blood Flow Velocity; Blood Vessels; Brain; Brain imaging; Brain region; Cardiac; Cardiopulmonary; Cardiovascular system; Cerebrovascular Circulation; Cerebrovascular system; Cerebrum; Clinical; Cognition; Cognitive; Cognitive aging; Data; Dementia; Deterioration; Development; Devices; Doppler Ultrasound; Elderly; Episodic memory; Equipment; Event; Exercise; Exercise stress test; Exhibits; Foundations; Functional Imaging; Functional Magnetic Resonance Imaging; Future; Goals; Heart Abnormalities; Heart Rate; Hippocampus (Brain); Hypertension; Image; Impaired cognition; Impairment; Individual; Lateral; Link; MRI Scans; Magnetic Resonance Imaging; Measures; Memory; Methods; Participant; Patients; Performance; Perfusion; Physical activity; Physiological; Prefrontal Cortex; Procedures; Public Health; Research; Resolution; Respiration; Respiratory physiology; Rest; Risk; Running; Signal Transduction; Specificity; Spin Labels; Stimulus; Structure; System; Taxes; Thallium Myocardial Perfusion Imaging Stress Test; Thinking; Time; Variant; Vascular Diseases; Walking; Work; Workload; age related; blood oxygen level dependent; blood oxygenation level dependent response; cardiorespiratory fitness; cerebral hemodynamics; cerebrovascular; cingulate cortex; cognitive function; cognitive performance; cognitive testing; critical period; design; executive function; heart function; high resolution imaging; imaging approach; imaging modality; imaging study; innovation; insight; middle cerebral artery; neuroimaging; neurophysiology; neurovascular; novel; novel marker; physical inactivity; relating to nervous system; respiratory; response; sedentary; treadmill; young adult

ABSTRACT Aging is associated with pervasive neural and cognitive decline, which is further accelerated by poor cardiorespiratory (CR) function. This intersection of cardiac and respiratory function with brain and cognitive aging is further highlighted by research demonstrating that vascular dysfunction is a major component of age- associated cognitive decline, likely underpinned by alterations in cerebrovascular reactivity. Importantly, cardiac, vascular, and respiratory functions change dynamically in response to physiological demands – changes that are not captured by the standard brain imaging approach, when subjects typically undergo Magnetic Resonance Imaging (MRI) while lying still. A more sensitive approach, therefore, is to use neuroimaging during physical activity, when cardiac, vascular, and respiratory functions are taxed. Extant studies using physical activity to elicit a CR challenge implement imaging methods that lack the spatial resolution to examine regional changes or acquire imaging data after the CR challenge, by which time heart rate and respiration have returned to baseline, thereby failing to probe a critical period that may be most sensitive to age-related changes in cerebral hemodynamics. Here we propose to elucidate neurovascular mechanisms of age-associated decline through the implementation of a novel, naturalistic, CR challenge during simultaneous functional MRI (fMRI). We do so using a unique “cardiostepper” device, a Stairmaster-like piece of equipment that attaches to the MRI table. By manipulating the intensity of physical activity during fMRI, we are able to observe real-time changes in neurophysiology as a function of CR workload. This innovation allows for the assessment of cerebral hemodynamics during physical activity in a similar way that a ‘cardiac stress test’ (asking patients to walk/run on a treadmill at increasing intensity) is used clinically to identify cardiac abnormalities that are not present at rest and only identifiable when the patient is under cardiopulmonary duress. In this proposal, 25 young and 25 older adults will undergo cognitive testing, maximal cardiopulmonary exercise testing (CPET), and MRI during exercise challenge. Specific Aim 1 is focused on the elucidation of age-related changes in (blood oxygenation level dependent) BOLD response during physical activity. During fMRI, a block-design CR challenge will be implemented. To explore downstream cerebral benefits of exercise, we will also acquire arterial spin labeling (ASL) MRI data pre- and post-CR challenge to examine whether cerebral blood flow is augmented subsequent to an exercise stimulus. Specific Aim 2 will examine whether the BOLD response during CR challenge is correlated with cognitive performance among young and older adults. The development of a paradigm to examine regionally-specific alterations in cerebral hemodynamics during physical activity, which places the CR system under duress, has the potential to serve as a biomarker for those at risk for neural and cognitive decline.

摘要 衰老与普遍的神经和认知能力下降有关，而贫困会进一步加速这种下降。 心肺（CR）功能。心脏和呼吸功能与大脑和认知功能的交叉 研究表明血管功能障碍是年龄的一个主要组成部分，这进一步凸显了衰老的重要性- 相关的认知能力下降，可能由脑血管反应性的改变所支持。重要的是， 心脏、血管和呼吸功能会根据生理需求动态变化， 当受试者通常经历标准脑成像方法无法捕获的变化时， 磁共振成像（MRI），而躺下。因此，一种更敏感的方法是使用 在体力活动期间，当心脏、血管和呼吸功能负荷时，进行神经成像。现存 使用体力活动引发CR挑战的研究采用了缺乏空间分辨率的成像方法， CR激发后检查区域变化或采集成像数据的分辨率，此时心脏 心率和呼吸已经恢复到基线，从而未能探测可能是最重要的关键时期。 对年龄相关的脑血流动力学变化敏感。在这里，我们建议阐明神经血管 通过实施一种新颖的、自然的CR挑战， 同步功能性磁共振成像（fMRI）。我们使用一种独特的“心脏起搏器”设备， 连接到MRI台的设备。通过控制身体活动的强度， 通过fMRI，我们能够观察到神经生理学的实时变化作为CR工作负荷的函数。这 创新允许以类似的方式评估身体活动期间的脑血流动力学， “心脏负荷试验”（要求患者在跑步机上以增加的强度行走/跑步）在临床上用于 识别静息时不存在且仅在患者处于低血糖状态时可识别的心脏异常。 心肺胁迫在这项提议中，25名年轻人和25名老年人将接受认知测试，最多 心肺运动试验（CPET）和运动挑战期间的MRI。具体目标1侧重于 说明在物理治疗期间BOLD反应的年龄相关变化（血氧水平依赖性） 活动在fMRI期间，将实施块设计CR挑战。探索下游大脑 运动的益处，我们还将在CR激发前后采集动脉自旋标记（ASL）MRI数据， 检查运动刺激后脑血流量是否增加。具体目标2将 检查CR激发期间的BOLD反应是否与认知表现相关， 年轻人和老年人。建立一个研究脑组织局部特异性改变的范例 身体活动期间的血液动力学使CR系统受到胁迫，有可能发挥作用 作为神经和认知能力下降风险的生物标志物。