The Anterior Cingulate Cortex and Cognitive Aging

描述（由申请人提供）： 在其他健康的老年退伍军人中，与认知功能下降（AACD）相关的认知功能下降已成为他们生活质量和经济可行性的主要障碍。在过去十年中，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，这是机构化的主要原因，既不受欢迎又昂贵。到目前为止，只有非特异性的干预措施存在的AACD。本研究项目的长期目标是了解认知老化的生物学机制，以预防或治疗认知老化。本项目的基本假设是前扣带皮层（ACC）通过代谢功能障碍和/或其与相关神经网络的功能连接在认知老化中起着早期和关键的作用。推论假设包括以下内容：1）老年人即使在个体水平上也会显示出静息ACC代谢低下的证据，这为AACD提供了潜在的生物标志物。2)ACC代谢将随着年龄和APOE 4基因型而下降，并将进一步预期转化为MCI。3)ACC代谢与执行功能测试的相关性最好，而与记忆功能测试的相关性最差。为了实现这些目标，该项目具有以下具体目标：1）在仔细表征的健康年轻和相关老年受试者的匹配组中，以横截面设计表征静息ACC代谢减退和功能连接（即，子/父对）。2)使用现有的规范性ADNI数据进行纵向设计，将静息ACC代谢作为年龄、APOE基因型、教育等的函数，并确定ACC代谢减退是否预测转化为MCI的患者。3)描述衰老相关ACC代谢减退的认知后遗症。这项工作的方法包括休息FDG PET，休息BOLD功能磁共振成像在3 T，神经心理学测试和神经信息学的创新融合。这项工作预计将建立ACC功能障碍，发生在其他健康的老龄化，与执行功能受损，是主要的神经基板AACD。在实现这些目标后，这项研究可以垂直地将该领域集中在ACC功能障碍上，以获得更多的还原论和机械方法，从而真正导致基本的，根本的进步。最终的潜在医学影响是预防和/或治疗AACD。

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.