ISOLATED EXECUTIVE IMPAIRMENT AND COGNITIVE DECLINE

孤立的执行力障碍和认知能力下降

• 批准号: 7234365
• 负责人: JULENE K JOHNSON
• 金额: $ 24.62万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7234365
• 关键词: Activities of Daily Living; Alzheimer' s Disease; Atrophic; Awareness; Brain; Clinical; Cognition; Cognitive; Cognitive aging; Cognitive deficits; Data; Dementia; Development; Differential Diagnosis; Elderly; Frontotemporal Dementia; Future; Goals; Impaired cognition; Impairment; Individual; Magnetic Resonance Imaging; Measurement; Measures; Memory; Performance; Prefrontal Cortex; Primary Prevention; Rate; Research Personnel; Risk; Score; Staging; Structure; Testing; Vascular Dementia; cerebral atrophy; entorhinal cortex; executive function; follow-up; frontal lobe; functional decline; functional disability; gray matter; mild neurocognitive impairment; neuroimaging; pre-clinical; programs; tool; treatment trial

DESCRIPTION (provided by applicant): The majority of studies of cognitive aging focus on memory decline and Alzheimer's disease (AD). However, the preclinical stage of AD and other dementias may also begin with impairment in non-memory cognitive domains. We have preliminary clinical and neuropathological data suggesting that isolated executive impairment, a non-memory cognitive deficit, may be a risk for the development of functional decline and/or dementia. The overall goal of this project is to test the hypothesis that an isolated impairment of frontalexecutive function in non-demented elderly will predict future cognitive decline / dementia, functional impairment, and brain atrophy. To test this hypothesis, we will obtain longitudinal cognitive, functional, and neuroimaging measurements of 48 elderly subjects with isolated executive impairment and compare with 48 subjects with amnestic mild cognitive impairment (MCI) and matched controls. Specifically, we predict that lower baseline performance on tests of executive function will be associated with 1) lower performance on functional measures (i.e., activities of daily living) at two- and four-year follow-up intervals and 2) a decline in cognitive performance at two- and four-year follow-up intervals when compared with matched controls. We also hypothesize that subjects with isolated executive impairment will have a greater degree of prefrontal cortex atrophy on MRI at baseline and show a faster rate of prefrontal cortex atrophy at the two-year follow-up interval. Across all subjects, we predict that there will a relationship between scores on tests of executive function and the degree of frontal cortex atrophy. This project will increase awareness of non-memory cognitive impairment as a significant risk for functional and cognitive decline and/or dementia, 2) provide clinical and neuroimaging tools for the identification of individuals with non-memory cognitive impairment for possible inclusion in future primary prevention and treatment trials, and 3) expand differential diagnosis with individuals who present with isolated executive impairment to include AD in addition to frontotemporal dementia, vascular dementia, etc.

描述（由申请人提供）：大多数认知老化的研究集中在记忆衰退和阿尔茨海默病（AD）。然而，AD和其他痴呆的临床前阶段也可能开始于非记忆认知领域的损伤。我们有初步的临床和神经病理学数据表明，孤立的执行功能障碍，非记忆认知缺陷，可能是发展功能下降和/或痴呆症的风险。该项目的总体目标是检验一个假设，即非痴呆老年人的额叶执行功能的孤立损伤将预测未来的认知衰退/痴呆，功能障碍和脑萎缩。为了验证这一假设，我们将获得48例孤立性执行功能障碍的老年受试者的纵向认知、功能和神经影像学测量结果，并与48例遗忘型轻度认知功能障碍（MCI）受试者和匹配的对照组进行比较。具体来说，我们预测执行功能测试的基线表现较低将与1）功能测量的表现较低（即，日常生活活动）和2）与匹配的对照组相比，在2年和4年的随访间隔认知能力下降。我们还假设，单独的执行功能障碍的受试者将有一个更大程度的前额叶皮层萎缩的MRI在基线和显示更快的速度，前额叶皮层萎缩在两年的随访间隔。在所有的受试者中，我们预测执行功能测试的分数和额叶皮层萎缩的程度之间会有关系。该项目将提高对非记忆性认知障碍作为功能和认知下降和/或痴呆症的重大风险的认识，2）提供临床和神经影像学工具，用于识别非记忆性认知障碍个体，以便可能纳入未来的初级预防和治疗试验，以及3）将存在孤立性执行障碍的个体的鉴别诊断扩展到除了额颞叶痴呆、血管性痴呆等之外还包括AD。