Midlife Brain Plasticity: Exercise and Vascular Function

项目总结 越来越多的证据表明，中年血管危险因素的存在(例如高血压和 糖尿病)会加速大脑老化，增加晚年患痴呆症的风险。相反，中年身体 活动与晚年患痴呆症的风险降低有关。有规律的有氧运动的潜在好处 运动对老年人神经认知功能的影响已被证实；然而，没有干预性研究 已经调查了这种对中年人的影响。因此，该项目的总体目标是 确定定期有氧运动对神经认知功能(主要结果)的影响以及 中年人脑神经可塑性和脑血管功能(继发结局) 亚临床心血管危险因素(即高血压前期和糖尿病前期)。我们将解决以下问题 目标。目的1：确定规律有氧运动对神经认知功能的影响。假设： 有规律的有氧运动可以改善体液认知能力。目标2：确定规则的效果 有氧运动对大脑可塑性的影响。假设：有规律的有氧运动增加前额叶和 海马体体积、胼胝体前部白质纤维完整性和大脑皮质功能连接性 默认模式网络。目标3：确定有规律的有氧运动对脑血流灌注的影响 以及它与神经认知功能和大脑可塑性的关系。假设：1)有规律的有氧运动 增加大脑皮层局部脑血流灌注，同时减弱脑血流(CBF)搏动性 2)与运动相关的脑血流灌注和脑血流搏动性的变化介导了脑血流动力学的改变 神经认知功能和大脑可塑性。为了达到我们的目标，我们将进行一项横断面研究 将耐力训练的成年人与久坐不动的受试者与亚临床心血管风险因素进行比较 2)对久坐不动的受试者进行为期一年的有氧运动的干预研究 训练或伸展。认知功能将使用NIH工具箱认知电池进行评估 辅以对注意力执行功能、间歇性和工作的敏感神经心理测试 内存和处理速度。脑结构和功能的神经成像生物标志物将通过以下方式获得 核磁共振检查。脑血流灌注和脑血流搏动性将通过动脉自旋标记、2D时间分辨相位- 增强磁共振成像和经颅多普勒检查。该项目的成功完成将提供迫切的 有规律的有氧运动是否改善中年人的神经认知功能 在晚年发展为认知衰退和痴呆症的高风险个体。

PROJECT SUMMARY Converging evidence indicates that the presence of midlife vascular risk factors (e.g. hypertension and diabetes) accelerates brain aging and increases the risk of dementia in late life. Conversely, midlife physical activity is associated with the reduced risk of dementia in late life. The potential benefits of regular aerobic exercise on neurocognitive function have been demonstrated in older adults; however, no interventional study has investigated such effects in middle-aged adults. Therefore, the overarching goal of this project is to determine the effects of regular aerobic exercise on neurocognitive function (primary outcome) as well as brain neuronal plasticity and cerebrovascular function (secondary outcomes) in middle-aged adults with subclinical cardiovascular risk factors (i.e. prehypertension and prediabetes). We will address the following aims. Aim 1: Determine the effect of regular aerobic exercise on neurocognitive function. Hypothesis: Regular aerobic exercise improves fluid cognitive performance. Aim 2: Determine the effect of regular aerobic exercise on brain plasticity. Hypothesis: Regular aerobic exercise increases prefrontal and hippocampal volumes, white matter fiber integrity in the anterior corpus callosum, and functional connectivity of the default-mode-network. Aim 3: Determine the impact of regular aerobic exercise on brain perfusion and its relation to neurocognitive function and brain plasticity. Hypotheses: 1) Regular aerobic exercise increases regional brain perfusion while attenuating cerebral blood flow (CBF) pulsatility in the large cerebral arteries; 2) The exercise-related changes in brain perfusion and CBF pulsatility mediate changes in neurocognitive function and brain plasticity. To address our aims, we will conduct 1) a cross-sectional study which compares endurance-trained adults with sedentary subjects with subclinical cardiovascular risk factors and 2) an interventional study in which those sedentary subjects undergo a 1-year program of aerobic exercise training or stretching. Cognitive function will be assessed using the NIH Toolbox Cognitive Battery complemented with sensitive neuropsychological testing on attention-executive function, episodic and working memory, and processing speed. Neuroimaging biomarkers of brain structure and function will be acquired by MRI. Brain perfusion and CBF pulsatility will be measured by arterial spin labeling, 2D time-resolved phase- contrast MRI, and transcranial Doppler. Successful accomplishment of this project will provide the urgently needed knowledge whether regular aerobic exercise improves neurocognitive function in middle-aged individuals who have high risks of developing cognitive decline and dementia in late life.