Older Breast Cancer Patients: Risk For Cognitive Decline

老年乳腺癌患者：认知能力下降的风险

• 批准号: 9238667
• 负责人: Tim Alan Ahles
• 金额: $ 75.74万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9238667
• 关键词: Admission activity; Affect; Age; Aging; Apolipoprotein E; Biological Markers; Breast Cancer Patient; Breast Cancer survivor; C-reactive protein; Cancer Survivorship; Caring; Catechol O-Methyltransferase; Characteristics; Clinical Treatment; Cognition; Cognitive; Cognitive aging; Consent; Control Groups; DNA; DNA Library; Data; Data Collection; Decision Making; Detection; Enrollment; Exposure to; Future; Genes; Genetic Polymorphism; Genotype; Health; Health Care Costs; Hormonal; Hospitals; Image; Impaired cognition; Inflammation; Inflammatory; Institute of Medicine (U.S.); Interleukin-6; Intervention Trial; Knowledge; Late Effects; Lead; Life; Life Style; Longitudinal Studies; Malignant Neoplasms; Measurement; Mediating; Monitor; Neuropsychological Tests; Outcome; Paper; Patient risk; Patients; Phase; Phenotype; Physical activity; Physicians; Physiological; Population; Prospective Studies; Prospective cohort; Psychosocial Factor; Public Health; Publishing; Reporting; Research; Risk; Risk Factors; Sampling; Specimen; Stress; Survivors; Systemic Therapy; TNFR-Fc fusion protein; Testing; Thinking; Woman; age group; aging brain; apolipoprotein E-4; base; biobehavior; cancer risk; cancer therapy; chemobrain; chemotherapy; cognitive function; cognitive testing; cohort; data integration; design; follow-up; functional decline; improved; inflammatory marker; innovation; insight; meetings; mortality; multidisciplinary; multiple chronic conditions; older women; performance tests; prevent; prospective; protective effect; psychosocial; public health relevance; survivorship; therapy development; treatment planning

 DESCRIPTION (provided by applicant): There are compelling data indicating that cancer and its therapies are associated with cognitive decline ("chemo-brain") in certain survivors. Cognitive decline is an important public health issue facing our aging nation since it is a strong predictor f functional decline, hospital admission, mortality, and healthcare costs. For women 60 and older ("older"), who represent 71% of the three million US breast cancer survivors, cognitive decline is especially salient, since even small declines have negative effects on daily life. While there are multiple studies in younger survivors showing both persistent and late cognitive problems, there are insufficient data on long-term trajectories of and risks for cognitive decline in older survivos since past research has had small samples of older survivors; lacked pre-treatment data; was uncontrolled; and/or did not include follow-up. In recognition of this important evidence gap, the Institute of Medicine issued a recent call for collection of data about factors that influence the course of cancer survivorship in older survivors, stressing cognitive outcomes. In this revised continuation, our multi-disciplinary team will use a bio-behavioral cancer and aging framework to fill this gap by leveraging the Thinking and Living with Cancer (TLC) cohort. TLC is the only prospective cohort of older breast cancer survivors evaluated pre-treatment and 12 months later that includes matched controls. We have made excellent progress, meeting enrollment targets, publishing 19 papers, and presenting two abstracts. We also have provocative preliminary results showing divergent trajectories by treatment and genotype, with APOE 4 positive chemotherapy-exposed survivors demonstrating dramatically steeper 12-month declines in several cognitive domains than other survivors and controls. Additionally, physical activity tended to decrease and multi-morbidity to increase the odds of 12-month decline. To understand longer-term trajectories of and risks for cognitive decline, we propose to conduct new assessments (24, 36, 48 months) of the TLC cohort, use banked DNA for COMT polymorphism testing, and add objective monitoring of physical activity and measurement of inflammatory markers. The aims are to: 1) ascertain trajectories of longitudinal cognitive function and test for differences in treatment exposure-control groups; 2) identify risk factors for cognitie decline in the 48 months post-enrollment and determine how effects are moderated by treatment exposure (chemotherapy>hormonal>control); and 3) assess how inflammatory products (CRP, IL6, and sTNFRII) co-vary with trajectories of cognition; and test if inflammation mediates effects of physical activity and multi-morbidity on cognitive decline. The results will have high impact by suggesting future mechanistic research and intervention trials, and supporting patient-physician discussions about treatment benefits and harms. Knowledge about whether trajectories of decline plateau, accelerate, or occur as late effects could improve survivorship care planning for older breast cancer survivors.

 描述（由申请人提供）：有令人信服的数据表明，癌症及其治疗与某些幸存者的认知能力下降（“化学脑”）有关。认知 衰退是我们老龄化国家面临的一个重要的公共卫生问题，因为它是功能衰退、住院、死亡率和保健费用的强有力的预测因素。对于60岁及以上的女性（占美国300万乳腺癌幸存者的71%）来说，认知能力下降尤其突出，因为即使是很小的下降也会对日常生活产生负面影响。虽然在年轻幸存者中进行的多项研究显示了持续性和晚期认知问题，但由于过去的研究中老年幸存者的样本量较小，缺乏治疗前数据，不受控制和/或不包括随访，因此关于老年幸存者认知下降的长期轨迹和风险的数据不足。认识到这一重要的证据差距，医学研究所最近呼吁收集有关影响老年幸存者癌症生存过程的因素的数据，强调认知结果。 在这个修订后的延续中，我们的多学科团队将使用生物行为癌症和衰老框架，通过利用癌症思考和生活（TLC）队列来填补这一空白。TLC是唯一一个在治疗前和12个月后评估的老年乳腺癌幸存者前瞻性队列，其中包括匹配的对照组。我们取得了很大的进步，达到了招生目标，发表了19篇论文，并提出了两个摘要。我们也有挑衅性的初步结果，显示治疗和基因型的不同轨迹，与APOE β 4阳性化疗暴露的幸存者表现出显着陡峭的12个月下降，在几个认知领域比其他幸存者和对照。此外，体力活动倾向于减少，多发病率增加了12个月下降的几率。 为了了解认知能力下降的长期轨迹和风险，我们建议对TLC队列进行新的评估（24，36，48个月），使用库DNA进行COMT多态性检测，并增加对体力活动的客观监测和炎症标志物的测量。目的是：1）确定纵向认知功能的轨迹 并检验治疗组与对照组的差异; 2）识别入组后48个月内认知功能下降的风险因素，并确定治疗暴露如何调节效应（化疗>激素>控制）;和3）评估炎症产物如何（CRP、IL 6和sTNFRII）与认知轨迹共变;并测试炎症是否介导身体活动和多种疾病对认知能力下降的影响。这些结果将通过建议未来的机制研究和干预试验，并支持患者-医生关于治疗益处和危害的讨论，产生很大的影响。了解下降的轨迹是否达到平台，加速或作为晚期效应发生，可以改善老年乳腺癌幸存者的生存护理计划。