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

描述(申请人提供)：认知功能衰退是老年人最担心的老龄化后果之一，即使是认知功能的微小变化也会严重影响功能、独立生活能力和生活质量。正常衰老时认知变化的轨迹受遗传、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的关系，但这些研究中的绝大多数都集中在较年轻的患者(65岁)，很少有研究集中在5年幸存者身上。然而，大多数癌症幸存者是老年人。此外，那些在较大年龄接受治疗的人可能更容易受到认知能力下降的影响，因为影响正常认知老化的因素可能会与癌症治疗相互作用，增加易感性。这项应用的目的是联合老年病学、神经心理学、肿瘤学和遗传学领域，研究一组老年、长期(5-15岁)乳腺癌幸存者和匹配的健康对照组中认知障碍的患病率和发展轨迹。使用前瞻性的纵向研究设计，我们将在控制共病和脆弱的同时追求以下特定目标：目标1：与对照组(年龄、种族和教育匹配)相比，检查APOE状态、吸烟史和治疗暴露对老年乳腺癌幸存者认知功能的关联。目标2：利用生长混合建模技术确定老年乳腺癌幸存者和对照组(年龄、种族和教育匹配)认知功能纵向变化的轨迹：目标3：探索认知储备、APOE、吸烟史和治疗暴露对研究开始时认知功能的关联以及纵向变化的模式。这项研究意义重大，因为它将填补关于增加老年乳腺癌幸存者认知能力下降风险的因素方面的一个主要知识空白。这些数据对于权衡不断增长的老龄化人口中癌症治疗的风险和好处至关重要。这项研究具有创新性，因为它将检验治疗暴露、基因多态和吸烟史在预测乳腺癌幸存者和控制共病和虚弱负担的对照组之间认知表现差异方面的相互作用。此外，纵向设计将通知是否弹道 癌症幸存者的认知变化与健康对照组(相变假说)相似，或者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以降低这一风险，最终目标是保护老年癌症幸存者的认知功能和福祉。

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.