Mechanisms of Spatial Cognitive Impairment in Neurodegenerative Disease

神经退行性疾病空间认知障碍的机制

• 批准号: 8493963
• 负责人: Katherine Laurel Possin
• 金额: $ 13.93万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8493963
• 关键词: Adult; Age; Aging; Alzheimer' s Disease; Amyloid; Anatomy; Animal Model; Animals; Antipsychotic Agents; Area; Automobile Driving; Basic Science; Behavioral; Biological Neural Networks; California; Clinic; Clinical; Clinical Research; Clinical Trials; Cognition; Cognitive; Cognitive deficits; Collaborations; Corpus striatum structure; Data; Data Set; Dementia; Development; Diagnostic Specificity; Differential Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Dissociation; Distress; Dorsal; Early Diagnosis; Enrollment; Environment; Evaluation; Frontotemporal Dementia; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Gold; Image Analysis; Impaired cognition; Impairment; International; K-Series Research Career Programs; Lateral; Lesion; Life; Link; Lobe; Magnetic Resonance Imaging; Medial; Memory; Mentored Patient-Oriented Research Career Development Award; Mentors; Methods; Metric; Monitor; Neurodegenerative Disorders; Neurologic; Neurologist; Neurology; Neuropsychological Tests; Parietal; Parkinson Disease; Pathologic; Patients; Performance; Play; Prefrontal Cortex; Process; Program Research Project Grants; Relative (related person); Research; Research Infrastructure; Research Personnel; Rest; Rodent; Role; San Francisco; Short-Term Memory; Side; Specificity; Staging; Structure; Symptoms; Syndrome; Techniques; Temporal Lobe; Testing; Universities; Variant; amyloid imaging; base; career; cognitive neuroscience; flexibility; frontal lobe; gray matter; improved; in vivo; innovation; interest; meetings; morris water maze; neuroimaging; novel; parent project; patient oriented; performance tests; public health relevance; relating to nervous system; research study; skills; virtual reality; white matter

DESCRIPTION (provided by applicant): This is an application for a K23 award for Dr. Katherine Possin, a neuropsychologist at the University of California, San Francisco Memory and Aging Center (MAC). Dr. Possin is establishing herself as a young investigator in patient-oriented clinical research of spatial cognition in neurodegenerative disease. This K23 award will provide Dr. Possin with the support necessary to accomplish the following goals: (1) to become an expert in the behavioral neurology of neurodegenerative disease; (2) to conduct clinical investigations of spatial cognition in neurodegenerative disease by adapting innovative methods from cognitive neuroscience; (3) to develop proficiency in advanced multimodal neuroimaging analyses; and (4) to develop an independent clinical research career. To achieve these goals, Dr. Possin has assembled a mentoring team comprised of a primary mentor, Dr. Bruce Miller, Director of the MAC, who conducts clinical investigations in neurodegenerative disease as the PI on a Program Project Grant (PPG) on Frontotemporal Dementia and an Alzheimer's Disease Research Center (ADRC); and three co-mentors: Dr. Joel Kramer, a neuropsychologist who is an international leader in the development of neuropsychological tests; Dr. Maria Luisa Gorno Tempini, a neurologist with expertise in structural MRI including diffusion tensor imaging; and Dr. William Seeley, a neurologist with expertise in resting state functional connectivity MRI. Spatial cognitive deficits are often among the earliest symptoms of neurodegenerative disease, yet spatial function tests used in current dementia evaluations lack the anatomic specificity to differentiate between pathologic causes of dementia including Alzheimer's disease (AD), Parkinson's disease (PD) with cognitive impairment, and behavioral variant Frontotemporal dementia (bvFTD). Early diagnosis is more than merely of academic interest due to the contraindication of neuroleptic drugs in PD and the promise of molecule-specific treatments on the horizon. Dr. Possin's research will dissect the specific components of spatial function targeted by each disease using rigorous assessment methods developed and validated within a cognitive neuroscience framework, including virtual reality navigation tests (Aim 1), and her research will elucidate the neural correlates of spatial performance using structural and diffusion tensor imaging analyses (Aim 2). In addition, her research will identify the functional neural networks related to important aspects of spatial processing that are disrupted in these diseases (Aim 3). The proposed research will use the existing infrastructure of the PPG and the ADRC to enroll 31 patients with early AD, 31 patients with PD, 31 patients with bvFTD, and 31 neurologically healthy controls. Via the parent projects, a rich dataset will be made available to Dr. Possin for analysis with the spatial cognitive data that includes multimodal neuroimaging, general neuropsychological testing, neurological exam, and functional evaluation data.

描述(由申请人提供)：这是为加州大学旧金山记忆和衰老中心(MAC)的神经心理学家Katherine Possin博士申请K23奖项。在面向患者的神经退行性疾病空间认知临床研究中，波辛博士确立了自己作为年轻研究员的地位。这一K23奖项将为Possin博士提供必要的支持，以实现以下目标：(1)成为神经退行性疾病的行为神经学专家；(2)通过采用认知神经科学的创新方法，对神经退行性疾病的空间认知进行临床调查；(3)熟练掌握先进的多模式神经成像分析；以及(4)发展独立的临床研究事业。为了实现这些目标，Possin博士组建了一个指导团队，成员包括：首席导师Bruce Miller博士，MAC主任，负责神经退行性疾病的临床研究；PI on a Program Project Grant(额颞叶痴呆项目拨款)和阿尔茨海默病研究中心(ADRC)；以及三位共同导师：神经心理学家Joel Kramer博士，神经心理测试开发的国际领先者；Maria Luisa Gorno Tempini博士，在结构磁共振成像(包括扩散张量成像)方面的专业知识；以及William Seeley博士，神经病学家在静息状态功能连接MRI方面的专业知识。空间认知障碍通常是神经退行性疾病的最早症状之一，然而目前痴呆评估中使用的空间功能测试缺乏区分阿尔茨海默病(AD)、帕金森病(PD)伴认知障碍和行为变异额颞叶痴呆(BvFTD)等痴呆的病理原因的解剖学特异性。早期诊断不仅仅是学术上的兴趣，因为帕金森病的神经抗精神病药物是禁忌症，而且有望在地平线上进行分子特异性治疗。波辛博士的研究将使用在认知神经科学框架内开发和验证的严格评估方法，包括虚拟现实导航测试(目标1)，剖析每种疾病所针对的空间功能的特定组成部分，她的研究将利用结构和扩散张量成像分析阐明空间表现的神经相关性(目标2)。此外，她的研究将确定与空间处理的重要方面相关的功能神经网络，这些方面在这些疾病中受到干扰(目标3)。这项拟议的研究将利用PPG和ADRC的现有基础设施，招募31名早期AD患者、31名PD患者、31名bvFTD患者和31名神经学健康对照。通过母项目，Possin博士将获得丰富的数据集，用于分析空间认知数据，其中包括多模式神经成像、一般神经心理测试、神经学检查和功能评估数据。