The Anterior Cingulate Cortex and Cognitive Aging

描述(由申请人提供)： 与年龄相关的认知衰退(AACD)在其他方面健康的老年退伍军人已经成为他们生活质量和经济生存能力的主要障碍。在过去的十年里，85岁及以上的退伍军人人数增加了两倍。AACD通常预示着痴呆症，这是住院的主要原因，既不受欢迎，也代价高昂。到目前为止，只有非特异性干预措施存在于AACD。这项研究计划的长期目标是了解认知老化的生物学，以便预防或治疗它。这个项目的基本假设是，前扣带回(ACC)通过其代谢功能障碍和/或其与相关神经网络的功能连接在认知衰老过程中发挥早期和关键的作用。推论包括以下假设：1)老年人即使在个体水平上也会表现出静息性ACC低代谢的证据，这为AACD提供了一个潜在的生物标志物。2)ACC代谢率随着年龄和APOE4基因的增加而下降，并可进一步预测向MCI的转化。3)ACC新陈代谢与执行功能测试的相关性最好，而不是与记忆功能测试相关。为了实现这些目标，该项目有以下具体目标：1)采用横断面设计，在经过仔细描述的健康年轻和相关年长受试者(即儿童/父母配对)的配对群体中，表现出静息的ACC低代谢和功能连接性。2)使用现有的标准化ADNI数据进行纵向设计，将ACC代谢作为年龄、载脂蛋白E基因、教育程度等因素的函数进行建模，并确定ACC低代谢是否预测转换为MCI的人。3)描述增龄性ACC代谢低下的认知后遗症。这项工作的方法包括静息FDG PET、3T静息FMRI、神经心理测试和神经信息学的创新融合。这项工作有望确定ACC功能障碍，发生在其他健康的老龄化期间，与执行功能受损有关，是AACD的主要神经底物。在实现这些目标后，这项研究可以垂直聚焦于ACC功能障碍，寻找更简单化和机械化的方法，真正导致基础的、根本性的进步。最终潜在的医疗影响是AACD的预防和/或治疗。

DESCRIPTION (provided by applicant): Age-associated cognitive decline (AACD) in otherwise healthy, elder veterans has surfaced as a major impediment to their quality of life and economic viability. In the last decade, the number of veterans aged 85 years and older has tripled. AACD often heralds dementia, the principal cause of institutionalization, both undesirable and costly. To date, only non-specific interventions exist for AACD. The long term goal of this research program is to understand the biology of cognitive aging so as to prevent or treat it. The fundamental hypothesis for this project posits the anterior cingulate cortex (ACC) plays an early and pivotal role in cognitive aging through dysfunction of its metabolism and/or of its functional connectivity to related neural networks. Corollary hypotheses include the following: 1) Elders will show evidence of resting ACC hypometabolism even at the level of the individual, providing a potential biomarker for AACD. 2) ACC metabolism will decline with aging and APOE4 genotype and will further anticipate conversion to MCI. 3) ACC metabolism will correlate best with tests of executive rather than mnemonic functions. To accomplish these goals, the project has the following specific aims: 1) Characterize in a cross-sectional design resting ACC hypometabolism and functional connectivity in matched groups of carefully characterized healthy young and related elder subjects (i.e., child/parent pairs). 2) Model in a longitudinal design using existing normative ADNI data resting ACC metabolism as a function of age, APOE genotype, education, etc. and determine whether ACC hypometabolism predicts those who convert to MCI. 3) Characterize the cognitive sequelae of aging-related ACC hypometabolism. The approach for this work consists of an innovative blending of resting FDG PET, resting BOLD fMRI at 3T, neuropsychological testing, and neuroinformatics. This work is expected to establish ACC dysfunction, occurring during otherwise healthy aging, is associated with impaired executive function and is the primary neurological substrate for AACD. Upon achieving these goals, this research can focus the field vertically upon ACC dysfunction for more reductionist and mechanistic approaches that can truly lead to basic, fundamental advances. The ultimate potential medical impact is the prevention and/or treatment of AACD.