EXECUTIVE DEFICITS AND FUNCTIONAL DECLINE IN MCI

早期阿尔茨海默病患者在认知监测和控制方面存在障碍 处理(即执行功能障碍[ED])。最近的证据表明，轻度认知障碍(MCI)老年人出现ED可能是痴呆的前兆。然而，执行功能包括几个不同的、可分离的认知过程，特定的执行缺陷与功能衰退的相关性尚未确定。此外，MCI已经有了不同的定义，确切地说，哪些患者是导致痴呆的功能衰退的高危患者尚不清楚。因此，这项研究的主要目标是：1)确定遗忘型和非遗忘型MCI患者特定的执行领域受损；2)确定特定的执行障碍对这些组的日常功能的不同影响程度；3)确定MCI亚型中的ED是否可以预测随后的功能下降，通过临床痴呆量表(CDR-SB)的方框总和来衡量；以及4)测试正常老年人和MCI患者的执行功能的因素分析模型。遗忘性MCI患者、非遗忘性MCI患者和正常对照组将被纳入研究对象。他们将通过18项认知任务进行研究，这些任务被用来评估执行功能的六个概念上不同的领域：1)优先反应的抑制；2)决策和判断；3)计划和排序；4)概念/规则学习和集合转移；5)自发的灵活性和生成性；6)工作记忆和资源共享。验证性因素分析将被用来检验和验证这一认知模型，如有必要，该模型将进行修改。评估受试者日常功能的问卷将由消息灵通的线人填写，以评估ED在日常生活中的影响。两个MCI组和正常对照组的执行因素得分将与多变量结果的回归模型进行比较。他们也将被检验为执行困难问卷和ADCS/MCI-ADL量表得分回归模型中的预测因子。所有参与者都将进行年度临床重新评估，并记录痴呆症事件。两年后，所有可用的受试者将通过执行功能任务和问卷进行重新审查。重测数据将使我们能够确定特定执行障碍的进展及其作为遗忘型和非遗忘型MCI痴呆前功能衰退标志物(CDR-SB评分)的预测有效性。

Patients with early AD exhibit impairments in the monitoring and control of cognitive processing (i.e., executive dysfunction [ED]). Recent evidence suggests that the appearance of ED in elderly persons with mild cognitive impairment (MCI) may be a precursor of dementia. However, executive function encompasses several different, dissociable, cognitive processes, and the relevance of particular executive deficits to functional decline has not yet been established. In addition, MCI has been variably defined, and precisely which patients are at high risk for functional decline leading to dementia is not yet clear. Therefore, the primary goals of this study are: 1) to determine the specific executive domains that are impaired in patients with amnestic and nonamnestic forms of MCI; 2) to determine the extent to which particular executive impairments affect everyday functioning differentially in these groups; 3) to determine whether ED among subtypes of MCI is predictive of subsequent functional decline, measured by the sum of boxes from the Clinical Dementia Rating scale (CDR-SB); and 4) to test a factor analytic model of executive functioning in normal elderly and those with MCI. Patients with amnestic MCI, nonamnestic MCI and normal control participants will be recruited. They will be studied with 18 cognitive tasks that are proposed to assess six conceptually distinct domains of executive function: 1) inhibition of prepotent responses; 2) decision-making and judgment; 3) planning and sequencing; 4) concept/rule learning and set shifting; 5) spontaneous flexibility and generativity; and 6) working memory and resource-sharing. Confirmatory factor analysis will be used to test and validate this cognitive model, which will be modified if necessary. Questionnaires assessing subjects' everyday functioning will be completed by knowledgeable informants to assess the impact of ED in daily life. The executive factor scores of the two MCI groups and the normal control group will be compared with regression models for multivariate outcomes. They will also be examined as predictors in regression models of scores on the Dysexecutive Questionnaire and the ADCS/MCI-ADL scale. All participants will have annual clinical re-evaluations, and incident cases of dementia will be recorded. Two years later, all available subjects will be re-examined with the executive function tasks and questionnaires. The re-test data will allow us to determine the progression of particular executive impairments and their predictive validity as pre-dementia markers of functional decline (CDR-SB score) in amnestic and nonamnestic MCI.