Can Behavior Shape Neural Health? Identifying Modifiable Factors to Prevent Cognitive Decline in Age

行为可以塑造神经健康吗？

• 批准号: 9924492
• 负责人: Kaitlin B Casaletto
• 金额: $ 19.9万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9924492
• 关键词: Accounting; Adult; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease risk; Animals; Antibodies; Axon; Behavior; Behavior Therapy; Behavioral; Biological; Biological Markers; Brain; Brain-Derived Neurotrophic Factor; California; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Clinical; Clinical Research; Cognition; Cognitive; Cognitive aging; Cohort Studies; Collaborations; Complex; Data; Data Collection; Dementia; Development; Diagnostic; Economics; Environment; Epidemiology; Exposure to; Faculty; Foundational Skills; Future; Goals; Health; Impaired cognition; Individual; Infrastructure; Injury; Institutes; Intervention; K-Series Research Career Programs; Knowledge; Leadership; Life; Life Style; Light; Measurement; Memory; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Modeling; Nerve Degeneration; Neural Pathways; Neurobiology; Neurodegenerative Disorders; Neurofibrillary Tangles; Neurology; Neuronal Dysfunction; Neuronal Plasticity; Neurons; Neurophysiology - biologic function; Neuropsychology; Pathway interactions; Patient-Focused Outcomes; Physical activity; Plasma; Play; Postdoctoral Fellow; Prevention; Prevention strategy; Prospective Studies; Proteins; Proteomics; Psychiatry; Public Health; Randomized; Reaction; Reporting; Research; Research Personnel; Research Project Grants; Resources; Risk; Role; S-nitro-N-acetylpenicillamine; Sampling; San Francisco; Self Stimulation; Severities; Shapes; Statistical Models; Structure; Synapses; Syndrome; Technology; Time; Training; Training Activity; Translating; Universities; Validation; Wisconsin; Work; active control; age related neurodegeneration; base; behavior measurement; brain behavior; brain cell; brain health; career; cognitive training; cohort; cost estimate; dementia care; environmental enrichment for laboratory animals; epidemiology study; experience; experimental study; improved; lifestyle factors; neurobehavior; neurobiological mechanism; neurofilament; neurogranin; neurological rehabilitation; patient oriented; postsynaptic; presynaptic; prevent; professor; protein biomarkers; randomized trial; relating to nervous system; response; skills; synaptotagmin I; training project; trial design; wearable device

PROJECT SUMMARY/ABSTRACT In this K23 career development award, Dr. Kaitlin Casaletto will develop training in biologically-targeted lifestyle strategies for the prevention of age-related cognitive decline. Dr. Casaletto is a postdoctoral fellow in clinical neuropsychology who will be transitioning to faculty at the University of California, San Francisco Memory and Aging Center (MAC). Her longer term goal is to become a leading clinical aging researcher developing behaviorally-based interventions to promote brain health and improve patient outcomes with age. Through the support of this K23 and the enriched transdisciplinary training environment and resources at the MAC, Dr. Casaletto aims to accomplish the following training goals: 1) gain expertise in the neurobiology of aging with a focus on environmentally modifiable pathways; 2) develop specialized proficiency in plasma and cerebrospinal fluid (CSF) biomarker analytic platforms for clinical research; 3) expand skills in randomized trial design; 4) translate the K23 training and findings into an R01 developing a behavioral intervention to prevent age-related neurodegeneration. To achieve these goals, Dr. Casaletto has assembled an exemplary mentorship team, including her primary mentor, Dr. Joel Kramer, a neuropsychologist with decades of research dedicated to the measurement of behavior and cognition in aging; co-mentor, Dr. Kristine Yaffe, a professor of neurology, psychiatry, and epidemiology who is a leader in the identification of lifestyle prevention factors in AD; collaborator, Dr. Lennart Mucke, a neurobiologist who investigates and directs a UCSF-affiliated institute characterizing the mechanisms of neurodegenerative diseases; collaborator, Dr. Henrik Zetterberg, a neurochemist who developed the CSF biomarkers proposed in this K23; collaborator, Dr. Adam Gazzaley, a neuroscientist who directs a research center developing technologies to optimize brain function; and collaborator, Dr. John Neuhaus, a biostatistician with expertise in advanced modeling of biomedical data. The overarching goal of the proposed study is to characterize the relationship between lifestyle cognitive and physical behaviors and proteomic markers of neural health in aging and AD. The central rationale is that neural plasticity occurs throughout adulthood, is dysregulated in AD, and can be induced with behaviors. Though modifiable lifestyle factors are estimated to account for >9 million AD cases worldwide, behavioral prevention strategies have not been neurobiologically-targeted, limiting their potency. First, we will determine the relationship between daily cognitive and physical behaviors and protein markers of neural function in plasma and CSF in adults at-risk for and with AD. These models will be replicated in an independent sample. Second, we will manipulate cognitive and physical behaviors using a randomized training experiment and determine the directional impact on neural protein concentrations. This translational project will identify daily activities that can be used to improve neural health in aging and, ultimately, be leveraged to develop behavior-based interventions to prevent AD.

项目摘要/摘要 在这个K23职业发展奖中，凯特琳·卡萨莱托（Kaitlin Casaletto）博士将开发针对生物学的培训 预防与年龄相关的认知能力下降的生活方式策略。 Casaletto博士是博士后研究员 临床神经心理学将过渡到旧金山分校的教师 内存和老化中心（MAC）。她的长期目标是成为领先的临床老龄化研究员 开发基于行为的干预措施，以促进大脑健康并随着年龄的增长而改善患者结局。 通过此K23的支持以及在 Mac，Casaletto博士旨在实现以下培训目标：1）在神经生物学方面获得专业知识 衰老，专注于环保途径； 2）发展血浆和血浆的专业水平 用于临床研究的脑脊液（CSF）生物标志物分析平台； 3）扩大随机试验的技能 设计; 4）将K23培训和发现转化为R01，开发行为干预以防止 与年龄有关的神经退行性。为了实现这些目标，Casaletto博士汇集了一个模范 指导团队，包括她的主要导师，神经心理学家Joel Kramer博士，数十年的研究 致力于测量衰老中的行为和认知；联合官员克里斯汀·亚菲（Kristine Yaffe）博士 神经病学，精神病学和流行病学是识别预防生活方式因素的领导者 广告;合作者，神经生物学家Lennart Mucke博士，调查和指导与UCSF相关研究所 表征神经退行性疾病的机制；合作者Henrik Zetterberg博士， 在此K23中提出的CSF生物标志物的神经化学家；合作者Adam Gazzaley博士， 神经科学家指导研究中心开发技术以优化大脑功能；和 合作者John Neuhaus博士是生物医学数据高级建模方面的专业知识。 拟议的研究的总体目标是表征生活方式之间的关系 衰老和AD中神经健康的认知和身体行为以及蛋白质组学标记。中央 理由是神经可塑性在整个成年期发生，在AD中失调，可以与 行为。尽管估计可修改的生活方式因素在全球范围内占900万个案例，但 行为预防策略尚未在神经生物学上靶向，从而限制了其效力。首先，我们会的 确定每日认知和身体行为与神经的蛋白质标记之间的关系 成人在AD和与AD的成年人的血浆和CSF的功能。这些模型将在 独立样本。其次，我们将使用随机训练来操纵认知和身体行为 实验并确定对神经蛋白浓度的方向影响。这个翻译项目将 确定可用于改善衰老神经健康的日常活动，并最终将 制定基于行为的干预措施以防止AD。