Computerized Cognitive Remediation in Geriatric Depression

老年抑郁症的计算机认知治疗

• 批准号: 8367382
• 负责人: Sarah Shizuko Morimoto
• 金额: $ 14.97万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-02 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8367382
• 关键词: Academic Medical Centers; Aftercare; Antidepressive Agents; Area; Brain; California; Clinical; Clinical Trials; Cognitive remediation; Data; Depressed mood; Development; Disease; Doctor of Medicine; Elderly; Equilibrium; Functional disorder; Funding; Future; Generations; Goals; Grant; Health Services Research; Impairment; Intervention; Knowledge; Learning; Major Depressive Disorder; Manuscripts; Memory; Mental Depression; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methodology; Methods; Montgomery and Asberg depression rating scale; Neurobiology; Neurocognitive Deficit; Neuronal Plasticity; Outcome; Participant; Patients; Performance; Pilot Projects; Preparation; Procedures; Process; Randomized; Research; Research Personnel; Research Project Grants; Research Training; Resistance; Role; Semantics; Severity of illness; System; Testing; Therapeutic; Training; Training Programs; Universities; Verbal Learning; Work; career; career development; clinically relevant; cognitive function; computer generated; computerized; depressive symptoms; design; disability; dosage; efficacy evaluation; executive function; experience; follow-up; geriatric depression; improved; improved functioning; indexing; medical schools; method development; normal aging; novel; older patient; programs; relating to nervous system; response; skills; tool; treatment response

DESCRIPTION (provided by applicant): The goal of this K23 Mentored Patient-Oriented Research Career Development Award is to gain the mentorship, training, and research experiences necessary to establish myself as an independent investigator focused on developing neurobiologically informed cognitive remediation interventions for geriatric depression. I am currently a research fellow at the Weill-Cornell Advanced Center for Interventions and Services Research (ACISR) for Late-Life Depression. My short-term goals are to refine the computerized cognitive remediation (CCR) intervention I developed with my mentors and to conduct a preliminary study to test its efficacy. Beyond serving as a training tool, the improved CCR methods will be critical for the next step in my career, an RCT of a streamlined version of my intervention supported by an R01 grant. These goals will be completed under the mentorship of George Alexopoulos, M.D. of the Weill-Cornell ACISR, Bruce Wexler, M.D., of Yale University School of Medicine, and a team of consultants at Weill-Cornell Medical College, Yale University School of Medicine, and Columbia University Medical Center. In geriatric depression, deficits in executive functions are common and disabling. We and others have documented that some executive dysfunctions and their underlying brain network abnormalities are associated with poor response to antidepressants. My own work suggests that a specific determinant of resistance to antidepressants is semantic strategy impairment. This impairment is evident on both verbal fluency and verbal memory tests. The identification of this specific and clinically relevant neurocognitive deficit was an essential ste in designing the proposed computerized cognitive remediation (CCR) intervention. The proposed training plan consists of formal coursework, seminars, targeted tutorials, collaborative studies, and manuscript preparation, all of which are planned with the goal of imparting knowledge and skills in the neurobiology and neural plasticity in normal aging, CCR method development, and clinical trials methodology. The process and content of the training experiences are designed in a way that it will provide the opportunity for me to benefit maximally from interaction with mentors, collaborators, and consultants, and prepare me to submit a future R01 application. In addition to the above training, I plan to conduct a research project that will function as the training ground for accomplishing my educational objectives. In my Research Plan, I propose to investigate whether computerized cognitive remediation for geriatric depression (CCR-GD) can improve the efficacy of antidepressant treatment in geriatric depression by targeting specific executive deficits and (by inference) their underlying neurobiologic abnormalities. The first aim of the project is to pre-pilot and revise CCR-GD to achieve an optimal balance of challenge, performance, and acceptability to participants. The resultant version of CCR-GD will be piloted in my Research Plan. I hypothesize that older adults with major depression who have received therapeutic dosages of antidepressants for at least 8 weeks who receive CCR-GD will show greater reduction in depressive symptoms (MADRS), and greater increases in semantic strategy than participants on antidepressants plus a control condition over 4 weeks. Additional exploratory analyses will examine whether benefits of CCR-GD will transfer to executive functions other than those targeted by the intervention, whether verbal semantic strategy impairment at baseline moderates the advantage of CCR-GD in reducing depressive symptoms, and whether change in semantic strategy is associated with change in depression scores. Finally, the ACISR follow-up research program may offer the opportunity to examine whether benefits of CCR-GD (over the control condition) in depressive symptoms and in semantic strategy are retained 12-weeks after treatment completion. PUBLIC HEALTH RELEVANCE: Late-life depression is a devastating disorder often accompanied by neurocognitive deficits. In addition to increasing the severity of the illness, and disability, specific deficits in executive functions have been found to predict poor treatment response to antidepressants. We propose a training program that will prepare the applicant for a research career focused on developing cognitive remediation interventions for geriatric depression targeting network abnormalities associated with executive dysfunction and poor clinical outcomes. If successful, this line of research may enrich existing treatments with interventions relying on novel mechanisms likely to help depressed older patients who have failed first line treatments.

描述（由申请人提供）：这项K23指导的以患者为导向的研究职业发展奖的目标是获得必要的指导，培训和研究经验，以确立自己是一名专注于开发神经生物学知情的认知恢复干预措施的独立研究者。我目前是Weill-Cornell高级干预与服务研究中心（ACISR）的研究员，用于抑郁症。我的短期目标是完善我与导师一起开发的计算机认知补救（CCR）干预措施，并进行初步研究以测试其功效。除了担任培训工具之外， 改进的CCR方法对于我职业生涯的下一步至关重要，这是由R01赠款支持的简化版本的RCT。这些目标将在耶鲁大学医学院的Weill-Cornell ACISR，Bruce Wexler，M.D。的M.D. George Alexopoulos的指导下完成。 在老年抑郁症中，执行功能的缺陷是常见的和残疾的。我们和其他人已经证明，某些执行功能障碍及其潜在的大脑网络异常与对抗抑郁药的反应不佳有关。我自己的工作表明，对抗抑郁药的耐药性的特定决定因素是语义策略障碍。这种障碍在言语流利性和言语记忆测试中都很明显。鉴定这种特定和临床相关的神经认知缺陷是设计拟议的计算机认知补救（CCR）干预措施的必不可少的Ste。 拟议的培训计划包括正式的课程，研讨会，有针对性的教程，协作研究和手稿准备，所有这些都计划在正常衰老，CCR方法开发和临床试验方法中授予神经生物学和神经可塑性的知识和技能的目标。培训经验的过程和内容的设计方式是，它将为我提供与导师，合作者和顾问互动最大程度地使我受益的机会，并为我提交未来的R01应用程序做好准备。 除了上述培训外，我还计划进行一个研究项目，该项目将充当实现我的教育目标的培训理由。在我的研究计划中，我建议研究计算机化的老年抑郁症（CCR-GD）是否可以通过靶向特定的执行缺陷和（通过推断）其潜在的神经生物学异常来提高抗抑郁治疗在老年抑郁症中的疗效。该项目的第一个目的是预先修订和修改CCR-GD，以实现对参与者的挑战，绩效和可接受性的最佳平衡。我的研究计划将驾驶CCR-GD的结果版本。我假设患有严重抑郁症的老年人至少接受了抗抑郁药的治疗剂量至少8周接受CCR-GD的抑郁症状（MADR）和语义策略的降低，而不是参与者在4周内对抗抑郁药加上对照状况的参与者的增加。其他探索性分析将检查CCR-GD的益处是否会转移到干预措施针对的行政功能之外的其他功能，是否在基线处的口头语义策略损害会使CCR-GD在减轻抑郁症状方面的优势，以及语义策略的变化是否与抑郁症分数的变化有关。最后，ACISR随访研究计划可能会提供机会检查CCR-GD（在控制条件上）在抑郁症状中的益处（在控制条件下）是否在治疗完成后仍保留12周。 公共卫生相关性：晚期抑郁症是一种毁灭性疾病，通常伴有神经认知障碍。除了增加疾病的严重程度和残疾之外，还发现了执行功能的特定缺陷，可以预测对抗抑郁药的治疗反应不佳。我们提出了一项培训计划，该计划将使申请人为研究职业做好准备，该研究职业专注于针对老年抑郁症的认知补救干预措施，针对与执行功能障碍和临床不良结果相关的老年抑郁症网络异常。如果成功的话，这项研究可能会通过干预措施来丰富现有的治疗方法，这些干预措施依赖于可能有助于抑郁症的第一线治疗失败的老年患者。