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

阿尔茨海默病临床前和临床阶段的感觉和运动流

基本信息

批准号：
10667484
负责人：
Jorge Sepulcre
金额：
$ 33.6万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10667484
关键词：
Address Affect Afferent Neurons Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer&apos s disease patient Amyloid Amyloid beta-Protein Auditory Brain Brain Diseases Cerebrum Clinical Cognitive Cohort Studies Data Dementia Deposition Development Disease Early Diagnosis Elderly Evaluation Future Gait General Hospitals Genotype Hearing Hippocampus Human Image Impaired cognition Impairment Individual Investigation Link Longitudinal Studies Magnetic Resonance Imaging Maps Massachusetts Measures Medicine Methods Modality Modeling Motor Motor Neurons Nature Nerve Degeneration Neurobehavioral Manifestations Neurodegenerative Disorders Neurology Neurons Neuropsychology Neurosciences Pathology Pathway Analysis Population Positron-Emission Tomography Predictive Value Process Proteins Research Role Sampling Sensory Smell Perception Stream Structure System Time Tissues Tracer Variant Visual abeta accumulation aging brain association cortex clinical biomarkers clinically relevant cohort entorhinal cortex experience extracellular follow-up graph theory insight multidisciplinary multimodality neuroimaging neuron loss neuronal circuitry novel novel strategies pre-clinical sensorimotor system sensory system smell test tau Proteins tau aggregation visual motor

项目摘要

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).

项目概要（摘要）阿尔茨海默病 (AD) 会导致感觉系统发生变化，例如嗅觉或听觉，并且正如纵向研究所示，运动领域有时先于认知症状。感觉和运动障碍在 AD 神经变性中的具体作用仍然很大程度上未知过程及其预测未来痴呆症的临床应用在本提案中，我们重点关注网络。我们假设 AD 神经变性是横向的。影响跨神经系统的连接流，涉及网络集成的多个领域，从因此，我们将研究功能流。将感觉和运动区域与关联皮层连接起来，以理清感觉运动的作用疾病的破坏及其与脑回路水平上的 tau 蛋白和淀粉样蛋白积累的关系。特别是，我们将使用功能连接 MRI、多模态 PET 神经影像（tau 和淀粉样蛋白示踪剂）、和图论指标来可靠地量化大脑组织中的感觉和运动回路变化来自马萨诸塞州综合医院当地哈佛大脑老化研究的临床前和临床 AD 样本我们的初步数据表明，网络分析可以提供高度准确的信息。老年人群中感觉运动系统连接性的地图，为以下方面提供了定量的坚实基础评估 AD 相关的大脑功能变化。在这项多学科研究中，我们将 1) 量化。衰老和 AD 中的感觉和运动功能流（目标 2）研究感觉和运动功能流的关联；具有 tau 蛋白和淀粉样蛋白沉积物的运动功能流（目标 2）；以及 3）研究感觉和运动后续连接发生变化（目标 3）。