Depression in Alzheimer's Disease-II

描述(申请人提供)：阿尔茨海默病(AD)背景下的抑郁症是一个严重的公共卫生问题，对患者及其照顾者造成严重的不利后果。关于与AD相关的抑郁症的病程或治疗方面的研究很少。这在一定程度上是由于缺乏有效的操作标准来定义AD的抑郁。最近，NIMH召集了一个专家共识小组，制定阿尔茨海默病抑郁症(DAD)的标准草案，并确定这一领域的研究重点。这些标准旨在促进对AD抑郁的病程和治疗的进一步研究。这项拟议的多中心研究的第一个目标是在一项为期12周的随机、对照、双盲试验中，确定患有DAD的患者是否对使用舍曲林的抗抑郁药物治疗有反应。第二个目标是确定AD患者早期治疗抑郁症是否会在24周内影响关键的非情绪结果，如认知、生活质量、日常生活能力和照顾者变量。第三个目标是通过评估其病程和治疗反应来验证DAD综合征，并将其与AD中其他抑郁症的诊断概念进行比较，历时六个月。这些目标与NIMH专家共识小组阐明的优先事项是一致的。符合DAD标准的130名患者和他们的照顾者将在五个临床中心被招募到这项研究中：约翰·霍普金斯大学、南加州大学、罗切斯特大学、宾夕法尼亚大学和南卡罗来纳医科大学。这项研究将由约翰·霍普金斯临床试验中心协调进行。在详细的基线特征之后，参与者将被随机接受舍曲林或安慰剂治疗至少12周，并跟踪观察长达24周。所有患者和照顾者都将接受针对阿尔茨海默氏症和抑郁症的心理社会干预。患者的结果将包括：抑郁障碍的全球改善、抑郁量表的评级、生活质量、认知功能、日常生活能力、行为障碍和不良事件。照顾者的结果将包括：抑郁、生活质量和护理负担。关于第一个研究目标，分析将比较两个治疗组在前12周的患者情绪结果。关于第二个研究目标，分析将比较两个治疗组在24周内患者关键AD患者结果(认知、功能、生活质量、行为)和照顾者结果的轨迹。关于第三个目标，分析将在阿尔茨海默氏症的背景下使用三种不同的综合征定义来研究抑郁症状和抑郁综合征的纵向过程：DAD、DSM-IV和根据经验得出的“阿尔茨海默氏症相关情感障碍”。使用症状量表或这些症状中的每一种来定义AD中抑郁的预测有效性将根据不同的研究结果和抗抑郁治疗的疗效进行纵向评估。

DESCRIPTION (provided by applicant): Depression in the context of Alzheimer's disease (AD) is a significant public health problem with serious adverse consequences for patients and their caregivers. There has been little research into the course or treatment of depression associated with AD. This is in part due to the absence of validated operational criteria for defining depression in AD. Recently, NIMH convened an expert consensus panel to develop draft criteria for depression of Alzheimer's disease (dAD) and to establish research priorities in this area. These criteria are intended to facilitate further studies of the course and treatment of depression in AD. The first aim of the proposed multicenter study is to determine whether individuals with dAD respond to antidepressant treatment using the medication sertraline in a 12-week randomized, controlled, double blind trial. The second aim is to establish whether earlier treatment of depression in AD affects critical non-mood outcomes such as cognition, quality of life, activities of daily living and caregiver variables, over 24 weeks. The third aim is to validate the dAD syndrome by evaluating its course and response to treatment in comparison to other diagnostic conceptualizations of depression in AD, over six months. These aims are consistent with priorities articulated by the NIMH expert consensus panel. 130 patients meeting criteria for dAD, and their caregivers, will be recruited into the study at five clinical centers: Johns Hopkins, University of Southern California, University of Rochester, University of Pennsylvania, and Medical University of South Carolina. The study will be coordinated by the Johns Hopkins Center for Clinical Trials. After detailed baseline characterization participants will be randomized to treatment with sertraline or placebo for at least twelve weeks and followed for up to 24 weeks. All patients and caregivers will receive psychosocial interventions for Alzheimer's and depression. Patient outcomes will include: global improvement of the depressive disturbance, ratings on a depression scale, quality of life, cognitive functioning, activities of daily living, behavioral disturbance, and adverse events. Caregiver outcomes will include: depression, quality of life, and care giving burden. Regarding the first study aim, analyses will compare the two treatment groups on patient mood outcomes in the first twelve weeks. Regarding the second study aim, analyses will compare the two treatment groups on the trajectories of patient critical AD patient outcomes (cognition, functioning, quality of life, behavior) and of caregiver outcomes over 24 weeks. Regarding the third aim, analyses will examine the longitudinal course of depressive symptoms and of depressive syndromes in the context of Alzheimer's using three different syndromic definitions: dAD, DSM-IV, and "Alzheimer's Associated Affective disorder" derived empirically. The predictive validity of defining depression in AD using a symptom scale or each of these syndromes will be assessed longitudinally against the various study outcomes, and against efficacy of response to antidepressant treatment.