MENTAL ILLNESS IN THE ELDERLY--DIAGNOSTIC TESTING

描述（改编自申请人摘要）：在第二次修订中 我们的竞争性更新申请，我们建议继续我们的工作， 以提高晚年精神疾病的诊断准确性。在 此外，我们提出了新的倡议，以确定生理指标， 痴呆症和抑郁症的预后，并发展生理 抗抑郁治疗反应的预测因子。的假设是 旨在解决临床重要性问题，并基于 重要的试点数据。针对委员会的批评，我们 对这个应用程序进行了重大修改。我们：1）使我们的 关于诊断和治疗的更具体的假设 抑郁症; 2）增加抑郁症组的受试者人数 从180例中的100例; 3）取消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 关于我们假设的机制; 6）包括新的 支持我们假设的试点数据，以及 我们的技术 该提案旨在：首先，完成QEEG作为一种方法的验证， 痴呆和抑郁症的鉴别诊断;二是使用QEEG 确定痴呆和抑郁症预后指标的方法; 第三，开发抗抑郁治疗的神经生理学预测因子 第四，检查白色的功能意义- 与综合MRI/QEEG的物质病变，并评估病变的作用 精神疾病的发展。我们将测试四个假设：1）QEEG 和谐和一致性是敏感和具体的措施， 诊断阿尔茨海默型痴呆（DAT），多发性梗死 痴呆（MID）、混合型DAT/MID痴呆（MIX）和抑郁症（DEP）; 2） 基线时的低一致性将与精神疾病的增加相关。 患者随访时的症状和功能状态下降 痴呆或DEP; 3）在病程中的一致性变化 抗抑郁治疗将预测对药物的反应;以及，4）A 相干性和MRI病变体积的组合将识别那些 复发风险增加的患者和正常对照（CON） 抑郁和认知和/或功能下降。要全面完成 通过四步计划实现这些目标。首先，我们将继续跟进 我们现有的DAT、MID和CON受试者队列，重点关注 功能残疾和行为症状的演变与 QEEG变量，并根据临床和QEEG的尸检验证- 基于诊断。第二，我们会招募轻微 痴呆或DEP，前瞻性地检查敏感性， QEEG诊断这些疾病的特异性，并确定 QEEG是治疗结果和长期预后的预测因素。第三、 我们会在治疗过程中仔细检查DEP受试者 以确定抗抑郁药反应的预测因子。四是 对DEP中的系列QEEG/MRI研究进行三维分析， CON受试者识别白质的类型和/或位置 与脑功能改变有关的疾病。系列研究将 确定损害的特征， 预后，以及QEEG监测的有用性 白质疾病的演变

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.