Vascular Effects on Normal Neural and Cognitive Aging

项目总结摘要 为Karen M.Rodrigue博士颁发的这一独立之路奖的目标是深化 应聘者在认知神经科学领域的专业知识，使她能够研究新问题 关于血管风险在大脑和认知老化中的作用。这个项目的中心目标是研究一个 衰老的血管假说，研究一般血管危险因素的作用，如高血压， 以及特定的脑血管机制，如低灌注率，在塑造神经和 正常衰老模型中的认知老化。拟议的K99阶段研究的重点是通过 验证与年龄相关的局部脑血流灌注改变预测认知能力下降的假设 健康的中老年人的表现。指导阶段还检查修改 在功能磁共振成像范式中，高血压对神经活动的影响，检验了以下假设 血管健康可以解释与年龄相关的脑功能去分化。有不同见解的人 在K99阶段，将使用寿命样本的差异法来检验假设。R00阶段 通过检查血管来扩展血管健康对神经和认知功能衰退的影响的研究 正常衰老中淀粉样蛋白沉积的预测因子。这项研究计划的目标与 国家老龄问题研究所的使命。了解血管健康对成功的贡献， 以及病理性衰老是非常重要的，因为在老年人中血管风险的盛行 人口及其预防和治疗的适宜性。研究人员获得的研究技能和知识 申请者在完成此项目(例如，功能磁共振成像、灌注和PET成像方面的培训)期间，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 成功地过渡到认知神经科学家的独立职位。

PROJECT SUMMARY ABSTRACT 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.