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
基本信息
- 批准号:8669705
- 负责人:
- 金额:$ 0.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:4 year oldAddressAdultAgeAge-associated memory impairmentAged, 80 and overAgingAging-Related ProcessAlzheimer&aposs DiseaseAnatomyAnteriorAreaBiologicalBiological PreservationBiological ProcessBrainCognitionCognitiveCognitive agingComplexControl GroupsDegenerative DisorderDementiaElderlyEvaluationFrequenciesGeneticGoalsHistopathologyImpaired cognitionIndividualLifeLinkLiteratureMagnetic Resonance ImagingMeasuresMediatingMemoryMicroscopicNeurobiologyNeurofibrillary TanglesNeuronsPathologicPerformancePersonsPopulationPrimatesProcessPublic HealthResearchResistanceSamplingScanningSenile PlaquesSpecimenStagingTestingThickTrainingUniversitiesage groupagedbasebrain behaviorbrain tissuecingulate cortexcognitive functioncohortdensityexecutive functionexperiencehigh riskinterestmild cognitive impairmentmultidisciplinaryneuroimagingneuromechanismneuropsychologicalnormal agingpeerpsychosocialpublic health relevancesocial cognitiontherapy developmentvirtual
项目摘要
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岁以上美国总人口的比例呈指数增长,从而增加了那些患痴呆症(例如阿尔茨海默氏病)风险最高的人的频率。拟议的研究通过研究似乎避免退行性疾病过程的人群来应对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”,即80岁以上的人,他们在日常生活中表现出了卓越的记忆力和繁荣。西北大学超级研究的目的是确定解释这些长寿人保留认知的解剖学,组织病理学,神经心理学,社会心理和遗传因素。一种可能的机制可能与对“正常”衰老和认知能力下降发生的病理大脑变化的抗性有关。有趣的是,在我们的中心,与对照组相比,超级量的MRI扫描对皮质厚度测量的初步分析发现前扣带回皮层(ACC)的厚度更大。此外,对超大脑的初步验尸定性检查显示出了不起的发现:(1)在ACC中,实际上缺乏阿尔茨海默氏病的斑块和缠结 - 缠结 - 缠结 - 缠结,以及(2)von经济神经元(Vens)的密度增加,这是更高的Primate Acc conse and Complece Complect and Comporte and Comemers and Comemers and Comporty and Comporty和更高级别的独特特征。该提案的目的是研究超级固定中扣带皮质的结构和病理特征,因为该区域被证明可以介导促进记忆的执行功能。 AIM 1将采用一种神经成像方法来对大量超级管理器和控制群中的扣留区域进行详细的利益分析,以识别可能代表超级传播所独有的解剖底物的扣带回区域。鉴于先前的发现,我们假设与对照组相比,超级词与其他扣带回区域的厚度将增加。 AIM 2将采用一种组织病理学方法来定量与衰老有关的后染后扣子的特征,包括斑块和缠结的标记和Vens的标记,在超级超级词和对照组的标本中。基于初步发现,与对照密度相比,超级捕获中的病理特征的频率预计将在超级词中最大。将分析AIM 1中解剖学测量与认知测试的性能之间的关系,以识别AIM 2中组织病理学特征与认知性能之间的关系〜的关系。这项多学科研究的发现将提供有关老年高级认知功能的神经机制的有价值信息。该项目是一个不可或缺的一部分的超级研究,它具有很高的转化,因为发现将有助于揭示神经生物学成分的衰老,最终可以指导痴呆症的治疗方法。神经影像学,组织病理学和认知评估的高级培训对于实现这些目标至关重要。
项目成果
期刊论文数量(0)
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Tamar D Gefen其他文献
Tamar D Gefen的其他文献
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Clinical, Neuroanatomic, and Pathologic Signatures of FTLD-tau in Dementia Phenotypes
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10529891 - 财政年份:2020
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Clinical, Neuroanatomic, and Pathologic Signatures of FTLD-tau in Dementia Phenotypes
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10755406 - 财政年份:2020
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Clinical, Neuroanatomic, and Pathologic Signatures of FTLD-tau in Dementia Phenotypes - Diversity Supplement
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Clinical, Neuroanatomic, and Pathologic Signatures of FTLD-tau in Dementia Phenotypes
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