Sensory and Motor Streams in Preclinical and Clinical Stages of Alzheimer's Disease

项目摘要(摘要) 阿尔茨海默氏症(AD)会导致感觉系统的变化，如嗅觉或听力，以及 运动领域有时先于认知症状，如纵向研究所示。然而，它 感觉和运动障碍在AD神经退行性变中的具体作用在很大程度上仍不清楚 预测未来痴呆发病的过程及其临床应用。在本提案中，我们将重点放在网络 衰老大脑中感觉和运动的性质变化。我们假设阿尔茨海默病的神经变性是横向的 影响涉及网络集成的多个域的神经系统之间的连接流，来自 感觉-运动到高级认知大脑中心。因此，我们将研究功能流 用联合皮质连接感觉和运动区以解开感觉-运动的作用 疾病的中断及其与tau和淀粉样蛋白在大脑回路水平堆积的关系。 特别是，我们将使用功能连接MRI、多模式PET神经成像(tau和淀粉样蛋白示踪剂)、 和图论测量方法，以可靠地量化大脑组织中感觉和运动回路的变化 临床前和临床AD样本来自我们在马萨诸塞州综合医院进行的当地哈佛衰老大脑研究 医院。我们的初步数据表明，网络分析可以提供高度准确的 老龄化人群感觉-运动系统连接性的量化图谱，为 评估阿尔茨海默病相关脑功能改变。在这项多学科的调查中，我们将1)量化 衰老和阿尔茨海默病的感觉和运动功能流(目标1)；2)调查感觉和运动功能之间的联系 运动功能流与tau和淀粉样蛋白沉积(目标2)；以及3)研究感觉和运动 后续行动中的连通性变化(目标3)。

Project Summary (Abstract) Alzheimer's disease (AD) causes alterations in sensory systems –such as olfaction or hearing-, and motor domains that sometimes precede cognitive symptoms, as shown in longitudinal studies. However, it remains largely unknown the specific role of sensory and motor disruptions within the AD neurodegeneration process and its clinical use for predicting future dementia onset. In this proposal, we focus on the network nature of sensory and motor changes in the aging brain. We postulate that AD neurodegeneration transversally affects connectivity streams across neuronal systems involving multiple domains of network integration, from sensory-motor to high-order cognitive brain centers. Thus, we will investigate the functional streams connecting sensory and motor regions with associative cortex to disentangle the role of sensory-motor disruption in the disease and its relationship with tau and amyloid accumulation at the brain circuit level. Particularly, we will use functional connectivity MRI, multimodal PET neuroimaging (tau and amyloid tracers), and graph theory metrics to reliably quantify the sensory and motor circuit changes in the cerebral tissue of preclinical and clinical AD samples from our local Harvard Aging Brain Study at Massachusetts General Hospital. Our preliminary data has demonstrated that network analysis can provide a highly accurate quantitative map of the sensory-motor systems connectivity in aging populations, offering a firm basis for assessment of AD related changes in brain function. In this multi-disciplinary investigation we will 1) quantify sensory and motor functional streams in aging and AD (Aim 1); 2) investigate the association of sensory and motor functional streams with tau and amyloid deposits (Aim 2); and 3) investigate the sensory and motor connectivity changes in the follow-up (Aim 3).