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: 10368146
• 负责人: Kaitlin B Casaletto
• 金额: $ 19.76万
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10368146
• 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 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; 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; modifiable 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.

项目概要/摘要 在这个 K23 职业发展奖中，Kaitlin Casaletto 博士将开展生物靶向培训 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，即将转任加州大学旧金山分校教师 记忆与衰老中心（MAC）。她的长期目标是成为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。 通过本次K23的支持以及学院丰富的跨学科培训环境和资源 MAC，Casaletto 博士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 关注环境可改变途径的老龄化； 2) 培养血浆方面的专业能力 用于临床研究的脑脊液（CSF）生物标志物分析平台； 3）拓展随机试验技能 设计; 4) 将 K23 培训和研究结果转化为 R01，制定行为干预措施以预防 与年龄相关的神经退行性疾病。为了实现这些目标，卡萨莱托博士收集了一个堪称典范的 导师团队，包括她的主要导师 Joel Kramer 博士，一位拥有数十年研究经验的神经心理学家 致力于测量衰老过程中的行为和认知；共同导师 Kristine Yaffe 博士，教授 神经病学、精神病学和流行病学领域的专家，在识别生活方式预防因素方面处于领先地位 广告;合作者 Lennart Mucke 博士是一名神经生物学家，负责调查并领导加州大学旧金山分校附属研究所 表征神经退行性疾病的机制；合作者，Henrik Zetterberg 博士 开发本 K23 中提出的脑脊液生物标志物的神经化学家；合作者 Adam Gazzaley 博士 神经科学家，领导一个研究中心开发优化大脑功能的技术；和 合作者 John Neuhaus 博士是一位生物统计学家，拥有生物医学数据高级建模方面的专业知识。 拟议研究的总体目标是描述生活方式与生活方式之间的关系 衰老和 AD 中的认知和身体行为以及神经健康的蛋白质组标记。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，并且可以通过 行为。尽管可改变的生活方式因素估计导致全球超过 900 万 AD 病例， 行为预防策略并未以神经生物学为目标，限制了其效力。首先，我们将 确定日常认知和身体行为与神经蛋白质标记物之间的关系 患有 AD 风险的成年人的血浆和脑脊液中的功能。这些模型将被复制到 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定向影响。该翻译项目将 确定可用于改善衰老神经健康的日常活动，并最终用于 制定基于行为的干预措施来预防 AD。

项目成果

Wearable Use in an Observational Study Among Older Adults: Adherence, Feasibility, and Effects of Clinicodemographic Factors.

老年人观察性研究中可穿戴设备的使用：依从性、可行性和临床人口统计学因素的影响。

• 发表时间: 2022
• 作者: Paolillo, Emily W;Lee, Shannon Y;VandeBunte, Anna;Djukic, Nina;Fonseca, Corrina;Kramer, Joel H;Casaletto, Kaitlin B
• 通讯作者: Casaletto, Kaitlin B

Baseline neuropsychological profiles in prion disease predict survival time.

朊病毒病的基线神经心理学特征可预测生存时间。

• 发表时间: 2020-09
• 作者: Sundaram, Saranya E;Staffaroni, Adam M;Walker, Nicole C;Casaletto, Kaitlin B;Casey, Megan;Golubjatnikov, Aili;Metcalf, Stacy;O'Leary, Kelly;Wong, Katherine;Benisano, Kendra;Forner, Sven;Gonzalez Catalan, Marta;Allen, Isabel E;Rosen, Howard J
• 通讯作者: Rosen, Howard J

Association of Physical Activity With Neurofilament Light Chain Trajectories in Autosomal Dominant Frontotemporal Lobar Degeneration Variant Carriers.

常染色体显性额颞叶变性变异携带者体力活动与神经丝轻链轨迹的关联。

• 发表时间: 2023-01-01
• 影响因子: 29
• 作者: Casaletto, Kaitlin B;Kornack, John;Paolillo, Emily W;Rojas, Julio C;VandeBunte, Anna;Staffaroni, Adam S;Lee, Shannon;Heuer, Hilary;Forsberg, Leah;Ramos, Eliana M;Miller, Bruce L;Kramer, Joel H;Yaffe, Kristine;Petrucelli, Leonard;Boxer, Adam
• 通讯作者: Boxer, Adam