Cognitive Remediation of Cognitive Control in Late-Life Depression

Manning博士是一位有执照的临床神经心理学家，专门从事老年人的认知评估。 他的临床实践和临床研究的重点是老年认知障碍和抑郁症。这 K23奖是他作为一名独立调查员职业生涯的关键一步， 改变晚年抑郁症（LLD）的病理生理过程。LLD是晚期痴呆症的风险状态。是 认为额叶边缘脑的变化会导致抑郁和认知缺陷， 增加LLD中痴呆的可能性。执行功能（EF）的轻度损害尤其出现在 与LLD有关。EF减弱在LLD中很常见，可预测治疗抵抗， 痴呆诊断这个过程似乎是动态的，在这个意义上，EF的减少促进了 抑郁症状和抑郁的增加导致EF的更大损害。干预的一种方式 将因此解决抑郁症状，例如，使用抗抑郁药和/或心理治疗。然而，在这方面， 抗抑郁药在LLD中具有相当有限的疗效和延迟的临床应答。此外，委员会认为， 抗抑郁药和心理治疗不能持续改善治疗后的EF。另一种方法是 因此，干预将是针对EF。我们建议使用计算机认知补救来改变EF， 抑郁症和执行控制连接，并探讨这种变化是否与 边缘系统连接和LLD的长期认知下降。 随着本奖项申请的重新提交，曼宁博士提出了一个培训和研究计划， 为研究与治疗反应和认知能力下降相关的机制提供了基础。 LLD.他有四个培训目标：1）扩大他对影响治疗反应的机制的知识， LLD的认知能力下降2)发展结构和功能MRI的采集和分析方面的专业知识。 3)获得认知补救干预措施的利用和评估方面的培训，以及4）学习临床 LLD治疗变化机制的试验设计和分析。为了回应评论者的 经过深思熟虑的批评，培训计划现在强调临床神经科学，MRI分析， 随机试验，以及临床前痴呆症识别研讨会。曼宁医生密切关注 使用结构和功能磁共振成像，敏感的认知评估，和纵向随访作为一个 意味着识别有认知能力下降风险的LLD患者。除了提供优秀的培训，这项研究 这种方法具有很强的潜力，阐明LLD的病理生理学。

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.