Exceptional Cognitive Aging: Neuropsychologic, Anatomic and Pathologic Correlates

描述（由申请人提供）：记忆投诉在老年人中很普遍，导致人们认为智力的逐渐丧失是老年人不可避免的一部分。 “正常”衰老。然而，最近来自我们80多岁和90多岁的“超级老年人”队列的试点数据表明，对于比他们年轻至少20到30岁的健康人来说，记忆测试分数可能达到或超过平均范围。我们的初步数据表明，超级老年人，目前的应用程序的重点，有更大的皮质体积（特别是在扣带皮层），更少的ApoE4的患病率，更多的von Economo神经元，和更少的阿尔茨海默氏症神经病理学的标志物比他们的认知平均年龄的同龄人。需要对更大的受试者群体进行纵向研究，并进行额外的神经病理学分析，以建立在这些发现的基础上，并在我们确定促进异常成功的认知老化的因素时，从影响中理清原因。该应用程序将研究一组八岁和九岁的人，他们的记忆表现至少达到50多岁和60多岁的平均水平，以便将时间的不可避免的后果与嵌入时间内的随机现象的累积但可预防的影响区分开来。到目前为止，34名超级老年人和10名正常老年人已经完成了首次访问（包括血液样本），>50%的这些受试者有纵向数据，100%的人已经同意或正在考虑捐献大脑，两个人已经去世并捐献了他们的大脑，证明了跟踪这个不寻常的认知老化队列的可行性。这项多学科研究将在一个非常适合本项目的环境中进行，其中包括一个具有认知神经科学和神经影像学，行为神经学，神经病理学和神经科学，神经心理学，生物统计学和MR物理学专业知识的研究人员团队。由NIA资助的西北AD中心将支持招募和收集更多数据。拟议研究的具体目的是：1）通过神经心理学表现以及MR和淀粉样蛋白PET成像建立超级老年人的纵向表型。2)调查老年人年龄相关斑块和缠结的患病率和密度，基底前脑胆碱能系统的状态和神经元数量。3)建立行为和生物学数据资源，以进一步共享资源并对超级老年人进行合作调查。通过识别有助于超级老年人高记忆表现的神经生物学特征，有可能帮助老年人避免疾病和残疾，提高生活质量并缓解迫在眉睫的公共卫生危机。

DESCRIPTION (provided by applicant): Memory complaints are widespread among the elderly, leading to the belief that a gradual loss of intellectual ability is an inevitable part of "normal" aging. However, recent pilot data from our cohort of "SuperAgers" in their 80s and 90s suggest that it is possible to have memory test scores at or above the average range for healthy individuals at least 20 to 30 years their junior. Our preliminary data demonstrate that SuperAgers, the focus of the current application, have larger cortical volumes (especially in the cingulate cortex), less prevalence of ApoE4, more von Economo neurons, and fewer markers of Alzheimer neuropathology than their cognitively average age peers. Longitudinal study of larger subject groups and additional neuropathologic analysis is needed to build on these findings and to disentangle cause from effect as we identify factors that promote unusually successful cognitive aging. This application will study a group of octo- and nona-genarians who have memory performance at least at an average level for individuals in their 50s and 60s in order to differentiate the inevitable consequences of time from the cumulative but preventable impact of stochastic phenomena embedded within time. Thus far, 34 SuperAgers and 10 normal agers have completed initial visits (including blood samples), >50% of these subjects have longitudinal data, 100% have agreed to or are considering brain donation, and two individuals have expired and donated their brains, demonstrating the feasibility of following this unusual cognitive aging cohort. This multidisciplinary study will take place in a setting ideally suited for this project, ith an established team of investigators with expertise in cognitive neuroscience and neuroimaging, behavioral neurology, neuropathology and neuroscience, neuropsychology, biostatistics and MR physics. The Northwestern AD Center, funded by the NIA, will support recruitment and collection of additional data. The Specific Aims of the proposed research will: 1) Establish the longitudinal phenotype of SuperAgers through neuropsychological performance as well as MR and amyloid PET imaging. 2) Investigate the prevalence and density of age-related plaque and tangle accumulation, status of basal forebrain cholinergic system and neuronal number in SuperAgers. 3) Establish a resource of behavioral and biological data for further resource sharing and collaborative investigations of SuperAgers. By identifying neurobiologic features that contribute to high memory performance in SuperAgers, it may be possible to help elderly avoid disease and disability, improve quality of life and alleviate a looming public health crisis.