Efficacy and target engagement of a digital intervention to improve the depression-executive dysfunction syndrome after stroke

数字干预改善中风后抑郁-执行功能障碍综合征的功效和目标参与度

• 批准号: 10525426
• 负责人: Abhishek Jaywant
• 金额: $ 19.55万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10525426
• 关键词: Address; Aftercare; Anterior; Antidepressive Agents; Attention; Awareness; Base of the Brain; Brain; Brain Injuries; Chronic; Clinical; Clinical Trials; Clinical Trials Design; Cognitive; Collaborations; Control Groups; Data; Data Analytics; Depressed mood; Digit structure; Educational workshop; Executive Dysfunction; Functional Magnetic Resonance Imaging; Goals; Grant; Impaired cognition; Individual; International; Intervention; Investigational Therapies; K-Series Research Career Programs; Knowledge; Left; Manuscripts; Measures; Mental Depression; Mentors; Mentorship; Modality; Modeling; Montgomery and Asberg depression rating scale; Mood Disorders; Neurosciences; Participant; Patient Self-Report; Patients; Performance; Preparation; Psychological Transfer; Randomized; Research; Research Personnel; Research Proposals; Rest; Role; Self Perception; Short-Term Memory; Side; Social Functioning; Standardization; Stroke; Syndrome; Testing; Time; Training; Treatment Efficacy; Writing; affective disturbance; base; career; career development; cognitive rehabilitation; cognitive testing; cognitive training; comorbidity; daily functioning; depressive symptoms; design; digital intervention; digital treatment; disability; efficacious treatment; efficacy evaluation; executive function; experience; functional MRI scan; functional outcomes; group intervention; improved; improved functioning; multitask; neuroimaging; neuropsychiatry; novel; personalized intervention; post intervention; post stroke; post stroke depression; programs; remote delivery; remote intervention; side effect; skills; stroke patient; stroke rehabilitation; stroke survivor; symposium; targeted treatment; therapeutic target; therapy design; treatment optimization; virtual

Project Summary/Abstract The goal of the proposed K23 Career Development Award is to provide the PI with the mentorship, knowledge, and skillset to develop into an independent investigator studying neuroscience-inspired, targeted therapeutics for comorbid mood and cognitive dysfunction after stroke. The PI's mentoring team will provide him with training in the brain-based mechanisms of mood disorders, use of functional MRI to examine target engagement, and clinical trial design and data analytic approaches. The training will incorporate individualized tutorials, formal coursework, national and international workshops and conferences, research collaboration, manuscript preparation, and grant writing. The training is integrated in a research proposal that evaluates the efficacy and target engagement of a digital intervention for the depression-executive dysfunction syndrome (DED) after stroke. Stroke is a leading cause of disability worldwide. Post-stroke DED is associated with more persistent depressive symptoms and executive dysfunction, worse social functioning, and greater loss of independence than post-stroke depression or executive dysfunction alone. Existing interventions have limited evidence of efficacy, side effects, and can be difficult for stroke patients to access. Novel and scalable approaches that target the mechanisms underlying post-stroke DED may yield more efficacious treatment. To address these barriers, the PI proposes to study a remote intervention for post-stroke DED that combines an iPad-based digital therapy called AKL-T01 that intensively trains rapid multitasking skills, together with virtual metacognitive coaching. AKL-T01 is designed to target a common mechanism underlying post-stroke depressive symptoms and executive dysfunction, which is reduced intrinsic functional connectivity in the executive control network (ECN). Virtual metacognitive coaching is included to address patient unawareness of deficits to enhance transfer of training gains to daily functioning. In this pilot clinical trial, N=70 patients with a first-time stroke and DED will be randomized to receive the intervention, or to a control condition with general and non-targeted cognitive stimulation together with metacognitive coaching. Participants will complete measures of executive dysfunction, depressive symptoms, and disability at baseline, week 3 (mid treatment), and week 6 (end treatment). Participants will complete resting state fMRI scans at baseline and week 6. Linear mixed-effects models will test the hypotheses that the intervention will be associated with greater improvements in executive function, depressive symptoms, and disability relative to the control group. Also tested is the hypothesis that the intervention group will have greater change in intrinsic functional connectivity in the ECN from baseline to week 6, relative to the control group. This project has the potential to address, in a scalable manner, a highly debilitating consequence of stroke. It will generate data that can be used to optimize treatment efficacy, further refine and personalize the intervention, and further validate a target for treatment.

Project Summary/Abstract The goal of the proposed K23 Career Development Award is to provide the PI with the mentorship, knowledge, and skillset to develop into an independent investigator studying neuroscience-inspired, targeted therapeutics for comorbid mood and cognitive dysfunction after stroke. The PI's mentoring team will provide him with training in the brain-based mechanisms of mood disorders, use of functional MRI to examine target engagement, and clinical trial design and data analytic approaches. The training will incorporate individualized tutorials, formal coursework, national and international workshops and conferences, research collaboration, manuscript preparation, and grant writing. The training is integrated in a research proposal that evaluates the efficacy and target engagement of a digital intervention for the depression-executive dysfunction syndrome (DED) after stroke. Stroke is a leading cause of disability worldwide. Post-stroke DED is associated with more persistent depressive symptoms and executive dysfunction, worse social functioning, and greater loss of independence than post-stroke depression or executive dysfunction alone. Existing interventions have limited evidence of efficacy, side effects, and can be difficult for stroke patients to access. Novel and scalable approaches that target the mechanisms underlying post-stroke DED may yield more efficacious treatment. To address these barriers, the PI proposes to study a remote intervention for post-stroke DED that combines an iPad-based digital therapy called AKL-T01 that intensively trains rapid multitasking skills, together with virtual metacognitive coaching. AKL-T01 is designed to target a common mechanism underlying post-stroke depressive symptoms and executive dysfunction, which is reduced intrinsic functional connectivity in the executive control network (ECN). Virtual metacognitive coaching is included to address patient unawareness of deficits to enhance transfer of training gains to daily functioning. In this pilot clinical trial, N=70 patients with a first-time stroke and DED will be randomized to receive the intervention, or to a control condition with general and non-targeted cognitive stimulation together with metacognitive coaching. Participants will complete measures of executive dysfunction, depressive symptoms, and disability at baseline, week 3 (mid treatment), and week 6 (end treatment). Participants will complete resting state fMRI scans at baseline and week 6. Linear mixed-effects models will test the hypotheses that the intervention will be associated with greater improvements in executive function, depressive symptoms, and disability relative to the control group. Also tested is the hypothesis that the intervention group will have greater change in intrinsic functional connectivity in the ECN from baseline to week 6, relative to the control group. This project has the potential to address, in a scalable manner, a highly debilitating consequence of stroke. It will generate data that can be used to optimize treatment efficacy, further refine and personalize the intervention, and further validate a target for treatment.