MENTAL ILLNESS IN THE ELDERLY--DIAGNOSTIC TESTING

描述(改编自申请人的摘要)：在第二次修订中 关于我们的竞争性续签申请，我们建议继续我们的工作 以提高老年精神疾病的诊断准确率。在……里面 此外，我们提出了新的倡议来确定生理指标 对痴呆症和抑郁症的预后进行预测，并发展生理学 抗抑郁药物治疗反应的预测指标。这些假设是 旨在解决临床上重要的问题，并基于 重要的试点数据。为了回应委员会的批评，我们已经 对此应用程序进行了重大修改。我们已经：1)制作了我们的 关于诊断和治疗的更具体的假设 抑郁症；2)增加抑郁组受试者的数量 从180人中的100人；3)取消了ECT作为可能的治疗方法；4)修订 我们的数据分析程序以控制可能的混淆 变量，包括功能的基线水平；5)添加了更多细节 关于我们的假设背后的机制；以及6)包括新的 支持我们假设的先导数据，以及临床应用 我们的技术。 这项建议的目的是：第一，完成qEEG作为一种 痴呆症和抑郁症的鉴别诊断；第二，使用qEEG 方法确定痴呆和抑郁症的预后指标； 第三，开发抗抑郁药物治疗的神经生理学预测指标 回应；第四，考察白色的功能意义-- 结合MRI/qEEG检查病变实质，并评价病变的作用 在精神疾病的发展中。我们将检验四个假设：1)QEEG 协调一致是敏感和具体的措施，以 多发梗死型阿尔茨海默型痴呆的诊断 痴呆(MID)、混合性DAT/MID痴呆(MIX)和抑郁症(DEP)； 基线的低连贯性将与精神疾病的增加相关 慢性阻塞性肺疾病患者随访时的症状和功能状态下降 痴呆症或副反应性痴呆；3)痴呆过程中的行为变化 抗抑郁药物治疗将预测药物反应；以及，4)A 结合相干性和MRI病变体积将确定 复发风险增加的患者和正常对照组(CON) 抑郁症，以及认知和/或功能衰退。我们将完成 这些目标通过一个四步计划实现。首先，我们会继续跟进。 我们现有的DAT、MID和CON主题队列，重点放在 功能性残疾的演变与行为症状的关系 到qEEG变量，并在尸检确认临床和qEEG- 基于诊断。第二，我们将招收新的温和的科目 痴呆或DEP，以前瞻性地检查敏感度和 定量脑电对这些疾病诊断的特异性及鉴别诊断 QEEG是治疗结果和远期预后的预测指标。第三, 我们将在治疗过程中深入检查副驾驶受试者。 以确定抗抑郁药物反应的预测因素。第四，我们将 在DEP中执行系列qEEG/MRI研究的三维分析 让受试者识别白质的类型和/或位置 与大脑功能改变有关的疾病。系列研究将 确定对长期有不利影响的损害的特征 预后，以及qEEG在监测预后方面的作用 白质疾病的进化。

DESCRIPTION (Adapted from applicant's abstract): In this second revision of our competitive renewal application, we propose to continue our work to enhance diagnostic accuracy in late-life mental illness. In addition, we propose new initiatives to identify physiologic indicators of prognosis in dementia and depression, and to develop physiologic predictors of antidepressant treatment response. The hypotheses are designed to address problems of clinical importance, and are based upon significant pilot data. In response to the Committee's critique, we have made significant revisions to this application. We have: 1) made our hypotheses more specific regarding the diagnosis and treatment of depression; 2) increased the number of subjects in the depressed group from 100 of 180; 3) eliminated ECT as a possible treatment; 4) revised our data analysis procedures to control for possible confounding variables, including baseline levels of function; 5) added more detail regarding mechanisms underlying our hypotheses; and 6) included new pilot data that support our hypotheses, and the clinical applications of our techniques. This proposal aims to: first, complete validation of QEEG as a method for the differential diagnosis of dementia and depression; second, use QEEG methods to identify indicators of prognosis in dementia and depression; third, develop neurophysiologic predictors of antidepressant treatment response; and, fourth, examine the functional significance of white- matter lesions with integrated MRI/QEEG, and assess the role of lesions in development of mental illness. We will test four hypotheses: 1) QEEG cordance and coherence are sensitive and specific measures for the diagnosis of dementia of the Alzheimer's type (DAT), multi-infarct dementia (MID), mixed DAT/MID dementia (MIX), and depression (DEP); 2) Low coherence at baseline will be associated with increased psychiatric symptoms and decreased functional status at follow-up in patients with dementia or DEP; 3) Changes in cordance during the course of antidepressant treatment will predict response to medication; and, 4) A combination of coherence and MRI lesion volume will identify those patients and normal controls (CON) at increased risk for recurrent depression, and cognitive and/or functional decline. We will accomplish these aims through a four-step plan. First, we will continue follow-up of our existing cohort of DAT, MID, and CON subjects, focusing on the evolution of functional disability and behavioral symptoms in relation to QEEG variables, and upon autopsy validation of clinical and QEEG- based diagnoses. Second, we will recruit new subjects with mild dementia or DEP, to prospectively examine the sensitivity and specificity of QEEG for diagnosis of these illnesses, and to identify QEEG predictors of treatment outcome and long-term prognosis. Third, we will intensively examine DEP subjects during the course of treatment to identify predictors of antidepressant response. Fourth, we will perform three-dimensional analysis of serial QEEG/MRI studies in DEP and CON subjects to identify the type and/or location of white-matter disease associated with altered brain function. Serial study will determine characteristics of lesions that adversely affect long-term prognosis, as well as the usefulness of QEEG for monitoring the evolution of white-matter disease.