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

项目总结/摘要 在K23职业发展奖中，Kaitlin Casaletto博士将在生物靶向领域开展培训， 预防与年龄相关的认知能力下降的生活方式策略。Casaletto博士是一名博士后研究员， 临床神经心理学，他将在加州大学旧金山弗朗西斯科任教 记忆与衰老中心（MAC）她的长期目标是成为一名领先的临床衰老研究人员 开发基于行为的干预措施，以促进大脑健康并改善患者随年龄增长的结果。 通过K23的支持和丰富的跨学科培训环境和资源， Casaletto旨在实现以下培训目标：1）获得神经生物学方面的专业知识， 衰老，重点是环境可改变的途径; 2）发展血浆和 用于临床研究的脑脊液（CSF）生物标志物分析平台; 3）扩展随机试验的技能 设计; 4）将K23培训和研究结果转化为R 01，制定行为干预措施，以预防 与年龄有关的神经退化为了实现这些目标，Casaletto博士组建了一个示范性的 导师团队，包括她的主要导师，乔尔克雷默博士，一个神经心理学家与几十年的研究 致力于测量行为和认知在老龄化;共同导师，博士克里斯汀Yaffe，教授 神经病学，精神病学和流行病学，他是确定生活方式预防因素的领导者， AD;合作者，LennartMucke博士，神经生物学家，调查并指导UCSF附属研究所 表征神经退行性疾病的机制;合作者，Henrik Zetterberg博士，a 神经化学家谁开发的CSF生物标志物提出在这个K23;合作者，亚当Gazzaley博士，一个 神经科学家，指导研究中心开发优化大脑功能的技术; 合作者John Neuhaus博士是一位生物统计学家，擅长生物医学数据的高级建模。 这项研究的总体目标是描述生活方式与 认知和身体行为以及衰老和AD中神经健康的蛋白质组学标志物。中央 基本原理是，神经可塑性发生在整个成年期，在AD中失调，并且可以被诱导， 行为。尽管据估计，可改变的生活方式因素导致全球超过900万例AD病例， 行为预防策略没有神经生物学靶向，限制了它们的效力。一是 确定日常认知和身体行为与神经元蛋白质标记物之间的关系， 在有AD风险和患有AD的成人中，这些模式将在一个 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性影响。该翻译项目将 确定可用于改善衰老中神经健康的日常活动，并最终用于 制定基于行为的干预措施来预防AD。

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.