Neurobiological Substrates of SuperAging and the Preservation of Cingulate Cortex

超级衰老的神经生物学底物和扣带皮层的保护

• 批准号: 8669705
• 负责人: Tamar D Gefen
• 金额: $ 0.4万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8669705
• 关键词: 4 year old; Address; Adult; Age; Age-associated memory impairment; Aged, 80 and over; Aging; Aging-Related Process; Alzheimer' s Disease; Anatomy; Anterior; Area; Biological; Biological Preservation; Biological Process; Brain; Cognition; Cognitive; Cognitive aging; Complex; Control Groups; Degenerative Disorder; Dementia; Elderly; Evaluation; Frequencies; Genetic; Goals; Histopathology; Impaired cognition; Individual; Life; Link; Literature; Magnetic Resonance Imaging; Measures; Mediating; Memory; Microscopic; Neurobiology; Neurofibrillary Tangles; Neurons; Pathologic; Performance; Persons; Population; Primates; Process; Public Health; Research; Resistance; Sampling; Scanning; Senile Plaques; Specimen; Staging; Testing; Thick; Training; Universities; age group; aged; base; brain behavior; brain tissue; cingulate cortex; cognitive function; cohort; density; executive function; experience; high risk; interest; mild cognitive impairment; multidisciplinary; neuroimaging; neuromechanism; neuropsychological; normal aging; peer; psychosocial; public health relevance; social cognition; therapy development; virtual

DESCRIPTION (provided by applicant): The proportion of the total US population over age 80 is rising exponentially, thus increasing the frequency of those who are at highest risk for developing dementias such as Alzheimer's disease. The proposed research addresses this major public health challenge by studying a population of individuals who seem to avoid degenerative disease processes. Our center identified a unique group of "SuperAgers", individuals over age 80 who demonstrate superior memory functioning and thrive in daily life. The goal of the SuperAging Study at Northwestern University is to identify the anatomic, histopathologic, neuropsychological, psychosocial, and genetic factors that explain preserved cognition in these long-lived persons. One possible mechanism may be linked with resistance to pathologic brain changes that occur with "normal" aging and cognitive decline. Interestingly, at our Center, preliminary analysis of cortical thickness measures from MRI scans of SuperAgers compared to control groups found greater thickness of the anterior cingulate cortex (ACC). Additionally, preliminary post-mortem qualitative examination of SuperAging brains revealed remarkable findings: (1) virtual absence of plaques and tangles-hallmarks of Alzheimer's disease- in the ACC and (2) increased density of von Economo neurons (VENS), a unique feature of the higher primate ACC implicated in complex reasoning and higher-order cognition. The goal of this proposal is to investigate structural and pathologic features of the cingulate cortex in SuperAgers, as this region is shown to mediate executive functions that facilitate memory. Aim 1 will employ a neuroimaging approach to conduct a detailed region-of-interest analysis of the cingulate in large groups of SuperAgers and controls to identify cingulate areas that may represent anatomic substrates unique to SuperAging. Given prior findings, we hypothesize that SuperAgers will have increased thickness in ACC vs. other cingulate regions compared to controls. Aim 2 will employ a histopathologic approach to quantitate features of post-mortem cingulate as they pertain to aging, including markers of plaques and tangles and counts of VENs, in specimens from SuperAgers and controls. Based on preliminary findings, the frequency of pathologic features in the cingulate is expected to be lower in SuperAgers compared to controls~ VEN density, however, is expected to be greatest in SuperAgers. Relationships between anatomic measures in Aim 1 and performance on cognitive tests will be analyzed to identify brain-behavior relationships~ relationships between histopathologic features in Aim 2 and cognitive performance will also be analyzed. Findings from this multidisciplinary study will provide valuable information on neural mechanisms underlying preservation of superior cognitive functioning in old age. The SuperAging Study, of which this project is an integral part, is highly translational as findings will help reveal the neurobiologic constituents f aging that can ultimately guide treatments for dementias. Advanced training in neuroimaging, histopathology, and cognitive assessment are critical for attainment of these goals.

描述（由申请人提供）：80 岁以上的美国总人口比例呈指数级上升，从而增加了患阿尔茨海默病等痴呆症的最高风险人群的频率。拟议的研究通过研究似乎避免退行性疾病过程的人群来解决这一重大公共卫生挑战。我们的中心确定了一群独特的“超级老年人”，他们年龄超过 80 岁，表现出卓越的记忆功能，并且在日常生活中表现出色。西北大学超级衰老研究的目标是确定解剖学、组织病理学、神经心理学、心理社会和遗传因素，以解释这些长寿者认知能力的保留。一种可能的机制可能与对“正常”衰老和认知能力下降时发生的病理性大脑变化的抵抗力有关。有趣的是，在我们的中心，与对照组相比，对超级老年人 MRI 扫描的皮质厚度测量值进行初步分析发现，前扣带皮层 (ACC) 的厚度更大。此外，对超级衰老大脑的初步尸检定性检查揭示了显着的发现：(1) ACC 中几乎不存在斑块和缠结（阿尔茨海默病的标志）；(2) 冯·伊科诺莫神经元 (VENS) 密度增加，这是一种独特的特征高等灵长类动物 ACC 与复杂推理和高阶认知有关。该提案的目标是研究超级老年人扣带皮层的结构和病理特征，因为该区域被证明可以调节促进记忆的执行功能。目标 1 将采用神经影像学方法对大组超级老化者和对照组的扣带回进行详细的感兴趣区域分析，以识别可能代表超级老化独特的解剖基质的扣带皮区域。鉴于之前的研究结果，我们假设与对照组相比，超级老年人的 ACC 区域厚度会比其他扣带回区域增加。目标 2 将采用组织病理学方法来定量死后扣带回与衰老相关的特征，包括超级老年人和对照样本中的斑块和缠结标记以及 VEN 计数。根据初步发现，与对照组相比，超级老年人扣带回病理特征的频率预计较低，但超级老年人的 VEN 密度预计最高。将分析目标 1 中的解剖测量与认知测试表现之间的关系，以确定大脑行为关系 ~ 目标 2 中的组织病理学特征与认知表现之间的关系也将被分析。这项多学科研究的结果将为老年人维持高级认知功能的神经机制提供有价值的信息。该项目是超级衰老研究的一个组成部分，该研究具有高度转化性，因为研究结果将有助于揭示衰老的神经生物学成分，从而最终指导痴呆症的治疗。神经影像学、组织病理学和认知评估方面的高级培训对于实现这些目标至关重要。