Aging trajectories and outcomes of older adults with acute myeloid leukemia

患有急性髓性白血病的老年人的衰老轨迹和结果

• 批准号: 10735257
• 负责人: Vijaya Raj Bhatt
• 金额: $ 61.07万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-12 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10735257
• 关键词: Activities of Daily Living; Acute Myelocytic Leukemia; Adult; Aftercare; Age; Aging; Attention; Auditory; BCL-2 Protein; Brain; Cognition; Cognitive; Cognitive aging; Data; Decision Making; Diagnosis; Disease; Disease remission; Dorsal; Education; Elderly; Electroencephalography; Enrollment; European Organization for Research and Treatment of Cancer; Event; Exercise; Goals; Hematologic Neoplasms; Impaired cognition; Impairment; Interdisciplinary Study; Knowledge; Longitudinal cohort study; Measures; Methods; Neuropsychological Tests; Neurosciences; Newly Diagnosed; Oncologist; Outcome; Participant; Patients; Physical Function; Quality of life; Questionnaires; Recommendation; Research; Risk; Risk Factors; Scientist; Short-Term Memory; Time; Visual; attentional control; cancer therapy; chemotherapy; cognitive function; cognitive process; cognitive reserve; comorbidity; comparison control; distraction; executive function; frailty; functional decline; functional improvement; functional independence; health related quality of life; improved; insight; instrumental activity of daily living; leukemia; leukemia treatment; multiple chronic conditions; neuroprotection; novel; novel strategies; novel therapeutic intervention; sex; shared decision making; success

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.

项目概要 在美国，超过三分之一的 60 岁以上患有急性髓系白血病 (AML) 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的丧失（如果他们选择化疗） 接受强化化疗。维奈托克和低强度化疗的组合提供了一种 然而，对于这种新方法，Venetoclax 存在一些知识空白。 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 其使用后的功能独立性以及增加此类风险的因素仍不清楚。 初步数据表明，许多患有 AML 的老年人的认知和身体状况稳定或有所改善 从诊断时到三岁时的功能、功能独立性和健康相关生活质量 (HRQOL) 新疗法几个月后，这些新发现凸显了新疗法在改善方面的成功。 尽管如此，仍发现了虚弱和多重疾病。 我们还利用了 NCI 推荐的神经科学方法和 在我们的研究中，成年人进行了脑电图（EEG）/事件相关脑电位（ERP）研究。 与健康成年人相比，血液癌症患者的背侧注意力和中枢神经活动活跃 治疗前确认这些发现将确定执行脑网络下降的风险。 注意力和执行功能、功能独立性和 HRQOL，并将提供新颖的机制 在拟议的纵向队列研究中，我们深入了解患有 AML 的老年人的大脑网络活动。 将招募新诊断为 AML 的老年人，他们将接受基于 Venetoclax 的治疗，并且年龄、 我们将比较两组的以下结果： 注意力和执行功能（追踪和其他神经心理学测试）、功能独立性、 HRQOL 和 EEG/ERP 测量（在听觉视觉分心任务期间进行 ERP 研究，以测量大脑活动） 入组时和 12 个月以上的研究目标是： 目标 1. 确定纵向注意力和执行力。 与年龄、性别和年龄相比，患有 AML 的老年人在以维奈托克为基础的治疗前后的功能 目标 2. 确定功能独立性和功能独立性的纵向变化。 患有 AML 的老年人与对照组的 HRQOL，并检查它们与纵向变化的关系 目标 3. 测量老年人大脑网络活动的纵向变化。 患有 AML 的成人在以维奈托克为基础的治疗之前和之后与对照组进行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 AML 患者的衰老研究。了解与稳定/改善功能轨迹相关的因素。 遵循新的治疗方法可以改变治疗范式，并且对于为关键决策提供信息至关重要 患有 AML 的老年人考虑对这种致命疾病进行化疗，这些目标与 NCI/NIA 的优先事项一致。

项目成果

Determining treatment tolerance and fitness for intensive chemotherapy in older adults with AML: a call to action.

确定患有 AML 的老年人对强化化疗的治疗耐受性和适应性：行动呼吁。

• 发表时间: 2024-02-08
• 影响因子: 20.3
• 作者: Bhatt, Vijaya Raj;Uy, Geoffrey L;Klepin, Heidi D
• 通讯作者: Klepin, Heidi D

Diet and Nutritional Supplementation in Patients With Cancer: Is More Necessarily Better?

癌症患者的饮食和营养补充：越多越好吗？

• 发表时间: 2024-03
• 影响因子: 4
• 作者: Dhakal, Prajwal;Bhatt, Vijaya Raj
• 通讯作者: Bhatt, Vijaya Raj