Vascular Effects on Normal Neural and Cognitive Aging

描述(由申请人提供)：为Karen M.Rodrigue博士颁发的这一独立之路奖的目标是加深候选人在认知神经科学领域的专业知识，使她能够研究关于血管风险在大脑和认知老化中的作用的新问题。这个项目的中心目标是检验衰老的血管假说，该假说调查一般血管风险因素(如高血压)和特定的脑血管机制(如低灌流)在正常衰老模型中塑造神经和认知衰老过程中的作用。拟议的K99阶段的研究集中在这一目标上，通过测试与年龄相关的区域脑血流灌注变化预测健康中老年人认知能力下降的假设。指导阶段还在fMRI范式中检查了高血压对神经活动的调节作用，检验了血管健康差异可以解释与年龄相关的大脑功能去分化的假设。在K99阶段，将使用寿命样本的横截面个体差异方法来检验假设。R00阶段通过检测正常衰老中血管淀粉样蛋白沉积的预测因子，扩展了血管健康对神经和认知能力下降的影响的研究。这项研究提案的目标与国家老龄研究所的使命是一致的。考虑到老年人口中血管风险的普遍存在及其预防和治疗的顺应性，了解血管健康对成功和病理性衰老的贡献是至关重要的。申请者在完成本项目期间获得的研究技能和知识(例如，功能磁共振成像、灌注和PET成像方面的培训)，以及培训计划中概述的拟议课程和专业发展活动，将使她能够成功过渡到认知神经科学家的独立职位。 公共卫生相关性：本提案检验了衰老的血管假说，该假说调查了一般血管风险因素(如高血压)和特定的脑血管机制(如低灌注率)在正常衰老模型中塑造神经和认知衰老过程中的作用。考虑到老年人口中血管风险的普遍存在及其预防和治疗的顺应性，了解血管健康对成功和病理性衰老的贡献是至关重要的。

DESCRIPTION (provided by applicant): The objectives of this Pathway to Independence Award for Karen M. Rodrigue, Ph.D., are to deepen the candidate's expertise in the field of cognitive neuroscience to enable her to investigate novel questions regarding the role of vascular risk in brain and cognitive aging. The central aim of this project is to examine a vascular hypothesis of aging which investigates the role of general vascular risk factors, such as hypertension, and specific cerebrovascular mechanisms such as hypoperfusion, in shaping the course of neural and cognitive aging within a normal aging model. The proposed K99 phase of research focuses on this aim by testing the hypothesis that age-related alteration in regional brain perfusion predicts decline in the cognitive performance of healthy middle-aged and older adults. The mentored phase also examines the modifying effects of hypertension on neural activity in an fMRI paradigm, testing the hypothesis that differences in vascular health can explain age-related dedifferentiation of brain function. A cross-sectional individual differences approach with a lifespan sample will be used to test hypotheses in the K99 phase. The R00 phase extends the study of the impact of vascular health on neural and cognitive decline by examining vascular predictors of ¿-amyloid deposition in normal aging. The objectives of this research proposal are in accord with the mission of the National Institute on Aging. Understanding the contributions of vascular health to successful, as well as pathological aging is fundamentally important given both the prevalence of vascular risk in the aging population, and its amenability to prevention and treatment. The research skills and knowledge gained by the applicant during the completion of this project (e.g., training in fMRI, perfusion and PET imaging) along with the proposed coursework and professional development activities outlined in the training plan, will enable her to successfully transition to an independent position as a cognitive neuroscientist. PUBLIC HEALTH RELEVANCE: The present proposal examines a vascular hypothesis of aging which investigates the role of general vascular risk factors, such as hypertension, and specific cerebrovascular mechanisms such as hypoperfusion, in shaping the course of neural and cognitive aging within a normal aging model. Understanding the contributions of vascular health to successful, as well as pathological aging is fundamentally important given both the prevalence of vascular risk in the aging population, and its amenability to prevention and treatment.