Cognitive Remediation of Cognitive Control in Late-Life Depression

曼宁博士是一名有执照的临床神经心理学家，专门研究老年人的认知评估。 他的临床实践和临床研究的重点是老年人的认知障碍和抑郁症。这 K23奖是他作为一名独立调查员的职业生涯迈出的关键一步，他专注于理解和 改善老年抑郁症(LLD)的病理生理过程。LLD是日后患痴呆症的危险状态。它是 认为额叶边缘大脑的变化会导致抑郁和认知缺陷，两者相互作用 增加LLD患痴呆症的可能性。执行功能(EF)的轻度损害尤其明显 与LLD相关。EF的缺陷在LLD中很常见，并预示着治疗耐药和更晚的 痴呆症诊断。这个过程似乎是动态的，从这个意义上说，EF的减少促进了 抑郁症状和抑郁程度的增加会导致EF的更大损害。干预的一种方式 因此，这将是为了解决抑郁症状，例如，使用抗抑郁药物和/或心理治疗。然而， 抗抑郁药在LLD中的疗效相当有限，临床反应延迟。此外， 抗抑郁药物和心理治疗并不能持续改善治疗后的EF。另一种手段是 那么，干预将是针对EF的。我们建议使用计算机化的认知补救来改变EF， 抑郁和执行控制连接性，并探索这种变化是否与 LLD的边缘连通性与长期认知功能衰退。 随着该奖项申请的重新提交，曼宁博士提出了一项培训和研究计划， 为研究治疗反应和认知功能减退的相关机制提供了基础。 LLD。他有四个培训目标：1)扩大他对影响治疗反应的机制的了解 LLD的认知功能减退。2)发展结构和功能磁共振成像的获取和分析方面的专业知识。 3)接受认知补救干预使用和评估方面的培训；4)学习临床 LLD治疗变化机制的试验设计与分析。对评论家的回答是 经过深思熟虑的批评，培训计划现在强调临床神经科学、核磁共振分析和 随机试验，以及临床前痴呆症识别研讨会。曼宁博士密切关注 使用结构和功能磁共振成像、敏感的认知评估和纵向随访作为 识别有认知衰退风险的LLD患者的方法。除了提供出色的培训，这项研究 该方法对于揭示LLD的病理生理机制具有很大的潜力。

Dr. Manning is a licensed clinical neuropsychologist who specializes in the cognitive evaluation of older adults. The focus of his clinical practice and clinical-research is cognitive disorders and depression in the elderly. This K23 Award is a critical step toward his career as an independent investigator focused on understanding and modifying pathophysiologic processes of late-life depression (LLD). LLD is a risk state for later dementia. It is thought that frontolimbic brain changes result in both depression and cognitive weaknesses that interact to increase the likelihood of dementia in LLD. Mild impairments in executive functions (EF) appear especially relevant to LLD. Weaknesses in EF are common in LLD and predictive of treatment resistance and a later dementia diagnosis. The process appears to be dynamic, in the sense that decrements in EF promote depressive symptoms, and increases in depression lead to greater impairment in EF. One way to intervene would thus be to address depressive symptoms, e.g., with antidepressants and / or psychotherapy. However, antidepressants have rather limited efficacy and a delayed clinical response in LLD. Furthermore, antidepressants and psychotherapy do not consistently improve EF post-treatment. The other means to intervene, then, would be to target EF. We propose to use computerized cognitive remediation to change EF, depression, and executive control connectivity and explore whether this change is associated with changes in limbic connectivity and long-term cognitive decline in LLD. With the resubmission of this Award application, Dr. Manning proposes a training and research plan that provides a foundation from which to study mechanisms related to treatment response and cognitive decline in LLD. He has four training goals: 1) Expand his knowledge of mechanisms affecting treatment response and cognitive decline in LLD. 2) Develop expertise in the acquisition and analysis of structural and functional MRI. 3) Obtain training in the utilization and evaluation of cognitive remediation interventions, and 4) Learn clinical trial design and analysis of mechanisms of therapeutic change in LLD. In response to the Reviewers' thoughtful critiques, the training plan now emphasizes coursework in clinical neuroscience, MRI analysis, and randomized trials, as well as workshops in preclinical dementia identification. Dr. Manning pays close attention to the use of structural and functional MRI, sensitive cognitive assessment, and longitudinal follow-up as a means to identify LLD patients at risk for cognitive decline. Beyond providing excellent training, this research approach has the strong potential to shed light on the pathophysiology of LLD.