Cognition In Older Breast Cancer Survivors: Treatment Exposure, APOE, & Smoking

老年乳腺癌幸存者的认知：治疗暴露、APOE、

• 批准号: 8577351
• 负责人: Tim Alan Ahles
• 金额: $ 73.33万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-25 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8577351
• 关键词: Acute; Adjuvant Chemotherapy; Adult; Affect; Aftercare; Age; Aging; Aging-Related Process; Animals; Apolipoproteins; Attention; Benefits and Risks; Brain; Breast Cancer Treatment; Cancer Control; Cancer Patient; Cancer Survivor; Cognition; Cognitive; Cognitive aging; Comorbidity; Data; Development; Diagnosis; Education; Elderly; Enrollment; Exposure to; Family; Foundations; Fright; Genetic; Genetic Polymorphism; Geriatrics; Goals; Growth; Health Status; Healthcare Systems; Image; Impaired cognition; Individual; Intervention; Knowledge; Life; Life Style; Long-Term Survivors; Longitudinal Studies; Malignant Neoplasms; Measures; Medical; Minor; Modeling; Morbidity - disease rate; Neuropsychological Tests; Neuropsychology; Nicotinic Receptors; Patients; Pattern; Performance; Personal Satisfaction; Phase; Population; Prevalence Study; Quality of life; Race; Research Design; Risk; Sampling; Smoker; Smoking; Smoking History; Structure; Survivors; Techniques; Therapeutic; Time; Treatment Factor; aging population; cancer therapy; chemotherapy; cognitive change; cognitive function; cognitive reserve; cohort; frailty; high risk; hormone therapy; human old age (65+); innovation; lifestyle factors; longitudinal design; malignant breast neoplasm; mortality; non-smoker; normal aging; older patient; older women; oncology; prevent; prospective; public health relevance

DESCRIPTION (provided by applicant): Cognitive decline is one of the most feared consequences of aging among older adults and even minor changes in cognitive function can seriously impact function, ability to live independently, and quality of life. The trajectory of cognitive change with normal aging is influenced by factors including genetics, cognitive reserve, lifestyle, frailty, and comorbid medical conditions. Although there are compelling data suggesting a relationship between cancer, cancer therapy, and cognitive impairment the vast majority of these studies have focused on younger patients (<65 years old) and few studies have focused on 5+ year survivors. However, the majority of cancer survivors are older adults. Furthermore, those who were treated at an older age may be more vulnerable to cognitive decline because factors that influence normal cognitive aging may interact with cancer treatments to increase vulnerability. The objective of this application is to unite the fields of geriatrics, neuropsychology, oncology, and genetics to study the prevalence and trajectory of cognitive impairment in a cohort of older, long-term (5-15 years) survivors of breast cancer and matched healthy controls. Using a prospective, longitudinal study design, we will pursue the following specific aims while controlling for comorbidity and frailty: Aim 1: Examine the association of APOE status, smoking history, and therapeutic exposures on the cognitive performance among older breast cancer survivors compared to controls (age-, race- and education-matched) Aim 2: Utilize Growth Mixture Modeling techniques to determine trajectories of longitudinal change in cognitive function among older breast cancer survivors and controls (age-, race- and education-matched): Aim 3: Explore associations among cognitive reserve, APOE, smoking history and therapeutic exposures on cognitive functioning at study entry and the pattern of longitudinal change. This study is significant because it will fill a major gap in knowledge regarding the factors that increase risk for cognitive decline in older breast cancer survivors. These data are critical in order to weigh the risks and benefits of cancer treatment in the growing aging population. This study is innovative because it will examine the interactions of therapeutic exposures, genetic polymorphisms, and smoking history in predicting differences in cognitive performance between breast cancer survivors and controls controlling for burden of comorbidity and frailty. Furthermore, the longitudinal design will inform whether the trajectory of cognitive change for cancer survivors parallels healthy controls (phase shift hypothesis) or demonstrates a steeper slope (accelerated aging hypothesis). These data will serve as a foundation to identify older breast cancer survivors at risk for cognitive impairment and guide the development of rationale interventions to decrease this risk, with the ultimate goal of preserving the cognitive function and well-being of older survivors of cancer.

描述（由申请人提供）：认知衰退是老年人最担心的衰老后果之一，即使认知功能发生微小变化也会严重影响功能、独立生活的能力和生活质量。正常衰老过程中认知变化的轨迹受到遗传、认知储备、生活方式、虚弱和合并症等因素的影响。尽管有令人信服的数据表明癌症、癌症治疗和认知障碍之间存在关系，但绝大多数研究都集中在年轻患者（<65 岁）上，很少有研究集中在 5 年以上的幸存者身上。然而，大多数癌症幸存者是老年人。此外，那些在较高年龄接受治疗的人可能更容易出现认知能力下降，因为影响正常认知衰老的因素可能与癌症治疗相互作用，从而增加脆弱性。 此应用程序的目的是将老年病学、神经心理学、肿瘤学和遗传学领域联合起来，研究一组老年、长期（5-15 年）乳腺癌幸存者和匹配的健康人中认知障碍的患病率和轨迹。控制。通过前瞻性、纵向研究设计，我们将在控制合并症和虚弱的同时追求以下具体目标： 目标 1：与对照组相比，检查 APOE 状态、吸烟史和治疗暴露与老年乳腺癌幸存者认知表现的关系（年龄、种族和教育程度匹配）目标 2：利用生长混合建模技术来确定老年乳腺癌幸存者和对照组（年龄、种族和教育背景）认知功能纵向变化的轨迹。目标 3：探索认知储备、APOE、吸烟史和治疗暴露与研究开始时认知功能以及纵向变化模式之间的关联。 这项研究意义重大，因为它将填补有关增加老年乳腺癌幸存者认知能力下降风险的因素的重大知识空白。这些数据对于权衡日益增长的老龄化人口中癌症治疗的风险和益处至关重要。这项研究具有创新性，因为它将检查治疗暴露、遗传多态性和吸烟史之间的相互作用，以预测乳腺癌幸存者和控制合并症和虚弱负担的对照组之间认知表现的差异。此外，纵向设计将告知轨迹是否 癌症幸存者的认知变化与健康对照组平行（相移假说）或表现出更陡峭的斜率（加速衰老假说）。这些数据将作为识别有认知障碍风险的老年乳腺癌幸存者的基础，并指导 制定合理的干预措施来降低这种风险，最终目标是保护老年癌症幸存者的认知功能和福祉。