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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).

项目摘要（摘要）