Cognitive and Neural Moderators of Longitudinal Decline in Frontotemporal Degeneration

额颞叶退化纵向下降的认知和神经调节因素

• 批准号: 9769210
• 负责人: Lauren M Massimo
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9769210
• 关键词: Affect; Aging; Award; Behavioral Research; Biological; Biological Factors; Biological Neural Networks; Brain; C9ORF72; Cerebrovascular Circulation; Clinical; Clinical Trials; Cognition; Cognitive; Collaborations; DNA Sequence Alteration; Data; Data Set; Delirium; Dementia; Deterioration; Development; Diffusion Magnetic Resonance Imaging; Discipline of Nursing; Disease; Education; Environment; Epidemiology; Fellowship; Financial compensation; Funding; Future; Genetic; Goals; Impaired cognition; Individual; Intervention; Intervention Studies; Knowledge; Laboratories; Laboratory Research; Learning; Leisure Activities; Leisures; Life Expectancy; Life Style; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mediating; Mentors; Mentorship; Methods; Modality; Mutation; National Research Service Awards; Nerve Degeneration; Neuroanatomy; Neurodegenerative Disorders; Neurons; Neuropsychological Tests; Neuropsychology; Neurosciences; Nurse Practitioners; Nurses; Nursing Research; Occupational; Occupations; PGRN gene; Pathology; Patients; Pennsylvania; Performance; Persons; Phase; Play; Positioning Attribute; Postdoctoral Fellow; Progressive Disease; Recommendation; Research; Research Methodology; Research Personnel; Research Priority; Research Support; Resources; Role; Schedule; Scientist; Spin Labels; Statistical Methods; Symptoms; Testing; Training; Universities; Work; base; behavioral variant frontotemporal dementia; burden of illness; career; clinically relevant; cognitive enhancement; cognitive function; cognitive neuroscience; cognitive performance; cognitive reserve; cognitive testing; cohort; college; density; design; executive function; experience; frontal lobe; frontotemporal degeneration; gray matter; improved; innovation; insight; interest; lifestyle factors; longitudinal dataset; longitudinal design; meetings; neurobiological mechanism; neuroimaging; pre-doctoral; prion-like; programs; rate of change; relating to nervous system; skills; symposium; symptom science; tau mutation; theories; therapy design; tool; white matter

Project Summary This K99/R00 award will support my development as an independent investigator with a research program designing individualized interventions to slow cognitive decline in persons with neurodegenerative disease that are based on underlying neurobiological mechanisms. Candidate: My clinical experience as a nurse practitioner and research experience in cognitive neuroscience ideally position me to achieve my career goal of becoming an independent investigator with expertise in the cognitive and biologic basis of neurodegenerative conditions such as Frontotemporal Degeneration (FTD). I had strong neuroscience training at the University of Pennsylvania, where I was supported by an NRSA Predoctoral Award to investigate the neural basis of apathy in behavioral variant Frontotemporal Degeneration (bvFTD). I was subsequently awarded an Individual NRSA Postdoctoral Fellowship to investigate how lifestyle factors contribute to longitudinal worsening in apathy. In this research, I have gained experience with longitudinal design and learned about additional MRI measures such as diffusion tensor imaging of white matter tracts. I have become increasingly interested in longitudinal cognitive decline and how lifestyle and biologic factors contribute to the variable rate of decline in bvFTD. In this proposal, I plan to gain the necessary expertise in the biological basis for symptom progression in neurodegenerative disease in order to design interventions for bvFTD. I will pursue training in intervention design and methods to prepare for a subsequent R01 where I will use the knowledge gained from this K99/R00 to design and test cognitive interventions that boost neural compensation to slow decline in bvFTD. Environment: This award will be conducted at The Pennsylvania State University (PSU), College of Nursing and the University of Pennsylvania, Frontotemporal Degeneration Center (UPenn FTDC). PSU and UPenn are leading centers for the study of neurodegenerative disease and I have strong institutional support from both universities. PSU is an exceptional environment that has expert centers for aging research and methodology including, non-pharmacological intervention research for individuals with neurodegenerative disease. My mentor, Dr. Donna Fick, is a nurse researcher with expertise in cognitive decline and she has a productive research program developing tailored interventions for persons with delirium and dementia based on cognitive reserve theory. Given my future goal of developing cognitive interventions, PSU is the ideal environment to pursue training in intervention methods. The UPenn FTDC is a leading center for biologic research in neurodegenerative disease including expert centers for genetic and neuroimaging research and relevant clinical research laboratories. The UPenn FTDC maintains one of the largest neurodegenerative disease datasets that includes a diverse range of modalities such as MRI, diffusion tensor imaging, arterial spin labeling, genetics, cerebrospinal and neuropsychological testing. My co-mentor, Dr. Murray Grossman, is the Director of the UPenn FTDC and thus will facilitate my development as an independent investigator by providing access to this unique dataset as well as laboratory resources and collaborations with other neuroimaging and genetic experts at UPenn. Training: I will develop my expertise in the cognitive and neural basis of longitudinal decline in neurodegenerative disease with the support of my mentor, Dr. Donna Fick, and my co-mentor, Dr. Murray Grossman. Specifically, I will engage in training related to longitudinal statistical methods, genetics, advanced neuroimaging skills and intervention design and methods. Each of these training modalities will be supported by complementary formal coursework, participation in seminars, attendance of conferences, and regularly scheduled meetings with my mentorship team. Research: bvFTD is a common cause of young-onset neurodegenerative disease and life expectancy is approximately 7 years, but this is highly variable. Recent studies have demonstrated the moderating effects of lifestyle and genetic factors on the clinical course of bvFTD. Neuroanatomic factors may also play a role in neural implementation of compensatory function, such as supporting alternate brain networks for optimal performance. The overall research aim of this proposal is to better understand the moderating effects of lifestyle and biologic factors on longitudinal decline in young-onset dementia, and an account of the mechanisms by which this occurs. This knowledge is crucial for the design of cognitive interventions that take advantage of compensatory mechanisms to enhance cognitive function and slow decline in neurodegenerative disease.

项目摘要 这个K99/R00奖将支持我作为一名独立调查员的发展 计划设计个体化干预措施以减缓患者的认知能力下降 基于潜在的神经生物学机制的神经退行性疾病。 应聘者：我作为护士从业者的临床经验和认知神经科学的研究经验 理想的定位是让我实现我的职业目标，即成为一名拥有 神经退行性疾病的认知和生物学基础，如额颞部退行性变(FTD)。我 我在宾夕法尼亚大学接受了很强的神经科学培训，在那里我得到了一名NRSA的支持 博士前奖研究行为变异型额颞部退行性变冷漠的神经基础 (BvFTD)。随后，我获得了NRSA博士后个人奖学金，研究生活方式 导致冷漠的纵向恶化的因素有很多。在这项研究中，我获得了经验 纵向设计并了解其他MRI措施，如白色扩散张量成像 物质轨迹。我对纵向认知衰退以及生活方式和生活方式越来越感兴趣 生物因素导致bvFTD下降的速度不同。在这项提案中，我计划获得必要的 神经退行性疾病症状进展的生物学基础方面的专业知识，以便设计 BvFTD的干预措施。我将继续接受干预设计和方法方面的培训，为后续的 在R01中，我将使用从K99/R00获得的知识来设计和测试认知干预 加强神经代偿，延缓bvFTD下降。 环境：该奖项将在宾夕法尼亚州立大学(PSU)护理学院举行 和宾夕法尼亚大学额颞部退化中心(UPenn FTDC)。PSU和UPenn是 领先的神经退行性疾病研究中心和我都得到了两家机构的大力支持 大学。PSU是一个特殊的环境，拥有老龄化研究和方法学的专家中心 包括神经退行性疾病患者的非药物干预研究。我的 导师唐娜·菲克博士是一名护士研究员，在认知能力下降方面拥有专业知识，她有一个富有成效的 为精神错乱和痴呆症患者制定基于认知的量身定做干预措施的研究计划 保留理论。考虑到我未来开发认知干预的目标，PSU是实现以下目标的理想环境 进行干预方法方面的培训。宾夕法尼亚大学自由贸易中心是美国领先的生物研究中心。 神经退行性疾病，包括遗传和神经成像研究及相关的专家中心 临床研究实验室。宾夕法尼亚大学FTDC保持着最大的神经退行性疾病之一 包括各种模式的数据集，例如MRI、扩散张量成像、动脉旋转 标记、遗传学、脑脊髓和神经心理测试。我的联合导师默里·格罗斯曼博士是 宾夕法尼亚大学自由贸易发展中心主任，因此将促进我作为独立调查员的发展，通过 提供对此独特数据集的访问以及实验室资源和与其他 宾夕法尼亚大学的神经成像和遗传学专家。 培训：我将在认知和神经基础上发展我的专业知识 神经退行性疾病，在我的导师唐娜·菲克博士和我的共同导师默里博士的支持下 格罗斯曼。具体地说，我将从事与纵向统计方法、遗传学、高级 神经影像技能及干预设计和方法。这些培训模式中的每一个都将得到支持 通过补充正规课程、参加研讨会、出席会议和定期 安排了与我的指导团队的会议。 研究：bvFTD是年轻发病的神经退行性疾病的常见原因，预期寿命是 大约7年，但这是高度可变的。最近的研究表明， 生活方式和遗传因素对bvFTD临床病程的影响。神经解剖学因素也可能在 神经实现补偿功能，例如支持交替大脑网络以实现最优 性能。这项建议的总体研究目的是为了更好地了解 生活方式和生物因素对青年起病痴呆纵向下降的影响，以及对 发生这种情况的机制。这一知识对认知干预的设计至关重要。 利用补偿机制来增强认知功能并减缓认知能力下降 神经退行性疾病。