Aging trajectories and outcomes of older adults with acute myeloid leukemia

项目总结 在美国，超过三分之一的60岁以上患有急性髓细胞白血病的老年人在没有接受任何治疗的情况下死亡 化疗，主要是由于担心认知能力下降和功能独立性丧失(如果他们选择 接受强化化疗。万乃馨和低强度化疗的组合提供了一种 治疗急性髓系白血病的有效新疗法。然而，关于这一新方法存在几个知识差距。文冠果 靶向神经保护性B细胞淋巴瘤2(Bcl-2)蛋白，但认知能力下降和丧失的实际风险 使用后的功能独立性以及增加此类风险的因素仍不清楚。我们的 初步数据显示，许多患有急性髓细胞白血病的老年人认知和身体状况稳定或有所改善 功能、功能独立性和健康相关生活质量(HRQOL)从确诊到三年 在新的治疗方法之后的几个月。这些新的发现强调了新的治疗方法在改善 认知功能、功能独立性与HRQOL尽管如此，还是发现了虚弱和多发病。 作为功能衰退的危险因素。我们还利用了NCI推荐的神经科学方法 进行脑电(EEG)/事件相关脑电位(ERP)研究。在我们的研究中，患有 与健康成人相比，血液病患者的背侧注意和中枢活动发生了改变。 治疗前的执行大脑网络。这些发现的确认将确定经济增长下降的风险 注意力和执行功能、功能独立性和HRQOL，并将提供新的机制 对急性髓细胞白血病老年患者大脑网络活动的洞察。在拟议的纵向队列研究中，我们 将招募患有新诊断的AML的老年人，他们将接受以静脉为基础的治疗，以及年龄- 性别和教育程度相匹配的非癌症对照组。我们将在以下结果上对两组进行比较： 注意力和执行功能(轨迹形成和其他神经心理测试)，功能独立性， HRQOL和EEG/ERP测量(在听觉-视觉分心任务期间进行的ERP研究，以测量大脑活动) 注册时及12个月以上。本研究的研究目标为：目标1.确定纵向注意和执行力 老年AML患者静脉滴注治疗前后的功能与年龄、性别和 教育程度相匹配的非癌症对照组。目标2.确定功能独立性的纵向变化和 老年急性髓系白血病患者与对照组的HRQOL比较，并检查它们与 注意力和执行功能。目的3.测量老年人大脑网络活动的纵向变化 成人急性髓系白血病患者使用万乃馨治疗前后与对照组的比较。这是第一项研究 应用严格的方法来克服先前研究的关键局限性，并推进当前有限的认知 急性髓系白血病患者的衰老研究。了解与稳定/改善的功能轨迹相关的因素 遵循新的治疗方法可以改变治疗模式，并对制定关键决策至关重要。 患有AML的老年人正在考虑为这种致命的疾病进行化疗。这些目标与NCI/NIA的优先事项保持一致。

PROJECT SUMMARY In the US, over one-third of older adults ≥60 years with acute myeloid leukemia (AML) die without receiving any chemotherapy, primarily due to concerns of cognitive decline and loss of functional independence if they chose to undergo intensive chemotherapy. A combination of venetoclax and low-intensity chemotherapy offers an effective new treatment for AML. However, several knowledge gaps exist about this new approach. Venetoclax targets neuroprotective B-cell lymphoma 2 (Bcl-2) proteins, but the actual risk of cognitive decline and loss of functional independence following its use, and the factors that increase such risks, are still unclear. Our preliminary data demonstrated that many older adults with AML had stable or improved cognitive and physical function, functional independence, and health-related quality of life (HRQOL) from the time of diagnosis to three months following newer treatments. These novel findings highlight the success of newer treatments in improving cognitive function, functional independence, and HRQOL. Despite this, frailty and multimorbidity were identified as risk factors for functional decline. We also utilized the NCI-recommended neuroscience approach and conducted electroencephalography (EEG)/event-related brain potential (ERP) studies. In our study, adults with hematological cancers versus healthy adults demonstrated altered activity in the dorsal attention and central executive brain networks prior to treatment. Confirmation of these findings will identify the risk of a decline in attention and executive function, functional independence, and HRQOL, and will provide novel mechanistic insights into the activity of brain networks in older adults with AML. In the proposed longitudinal cohort study, we will enroll older adults with a new diagnosis of AML who will receive venetoclax-based treatments, and age-, sex-, and education-matched non-cancer controls. We will compare the two groups on the following outcomes: attention and executive function (Trail Making and other neuropsychological tests), functional independence, HRQOL, and EEG/ERP measures (ERP studies during auditory-visual distraction tasks to measure brain activity) at enrollment and over 12 months. The study aims are: Aim 1. Determine the longitudinal attention and executive function of older adults with AML before and after venetoclax-based treatment, as compared to age-, sex-, and education-matched non-cancer controls. Aim 2. Determine longitudinal changes in functional independence and HRQOL in older adults with AML versus controls, and examine their associations with longitudinal changes in attention and executive function. Aim 3. Measure longitudinal changes in the activity of brain networks of older adults with AML before and after venetoclax-based treatment, as compared to controls. This is the first study to apply rigorous methods to overcome key limitations of prior studies and to advance the current limited cognitive aging research in patients with AML. Understanding factors associated with stable/improved functional trajectory following new treatment can change treatment paradigms and is essential to inform critical decision-making of older adults with AML considering chemotherapy for this fatal disease. The goals align with the NCI/NIA priorities.