Cognitive Aging, Alzheimers disease, and Cancer-related Cognitive Decline

认知衰老、阿尔茨海默病和癌症相关的认知能力下降

• 批准号: 10617392
• 负责人: Jeanne Mandelblatt
• 金额: $ 59.55万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10617392
• 关键词: Acute; Address; Affect; Aftercare; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease risk; Alzheimer' s disease therapy; Amyloid beta-Protein; Apolipoprotein E; Biological; Biological Markers; Biological Specimen Banks; Brain; Brain imaging; Brain-Derived Neurotrophic Factor; Breast Cancer survivor; Cancer Etiology; Cancer Survivor; Clinical; Cognition; Cognitive; Cognitive aging; Cohort Studies; Collaborations; Consent; Data; Data Analyses; Dementia; Disease; Education; Eligibility Determination; Episodic memory; Exclusion; Family history of; Female; Female Breast Carcinoma; Frequencies; Funding; Future; Genetic; Genotype; Geriatrics; Geroscience; Goals; Health; Heterogeneity; Hippocampus; Hormonal; Hormone use; IL8 gene; Image; Impaired cognition; Impairment; Indiana; Individual; Inflammation; Inflammatory; Interleukin-10; Interleukin-6; Language; Late Onset Alzheimer Disease; Life; Light; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Mediating; Memory; Menopause; Molecular; Morbidity - disease rate; Neuropsychological Tests; Obesity; Older Population; Pathologic; Pathology; Pathway interactions; Pattern; Physical activity; Plasma; Population; Prevention; Process; Prospective cohort; Protocols documentation; Publishing; Quality of life; Race; Reporting; Research; Research Personnel; Risk; Risk Factors; S100 Proteins; Short-Term Memory; Site; Sleep Disorders; Social isolation; Specimen; Survivors; TNF gene; Testing; Thinking; Time; Universities; Visuospatial; Woman; brain volume; cancer-related cognitive impairment; chemotherapy; clinically significant; cognitive change; comorbidity; conditioned fear; data de-identification; demographics; design; executive function; gray matter; hormone therapy; inflammatory marker; innovation; insight; male; malignant breast neoplasm; meetings; mortality; neurofilament; non-genetic; novel; risk sharing; secondary analysis; tau Proteins; tau-1

ABSTRACT As the US population ages, it is increasingly important to understand heterogeneity in cognitive aging including pathologic conditions like Alzheimer’s disease (AD) and cancer-related cognitive decline (CRCD). There is data to suggest that CRCD and AD share important cognitive aging features. The objective of this secondary data analysis project is to test if older breast cancer survivors with CRCD have clinical-pathological features of AD, including AD-pathology biomarker abnormalities, cognitive changes, brain imaging alterations, and similar risk factor profiles. To accomplish this goal, we will use existing de-identified data and banked specimens from the Thinking and Living with Cancer (TLC) study cohort. TLC includes female breast cancer survivors ages 60- 98 years old assessed pre-treatment and annually for up to 60 months and an equal number of contemporaneously assessed non-cancer controls (n=700/group). Consent included future use of data and specimens for new research purposes. Studying older breast cancer survivors is logical since they are already facing cognitive aging, CRCD has been described most often in breast cancer, the survivors are in the age range where non-cancer populations with APOE-4 develop AD, AD rates are higher in females vs. males, and 35% of TLC survivors already have global cognitive decline based on significantly greater change than the non-cancer controls. Longitudinal TLC data include scores on neuropsychological tests of memory, executive functioning, language, and visuospatial abilities; demographics; AD risk factors; and inflammation markers (IL- 6, TNF-a, IL-8, IL-10, IFNg, CRP). We add to these data by using banked specimens to test plasma AD- pathology biomarkers (Aβ1-42, tau, p-tau, and neurofilament light chain [NFL]) and danger-associated molecular patterns (DAMPs: Aβ, S100 proteins, and HMBG1). A sub-set of TLC survivors at Indiana University has baseline and 12-month MRI data using the NIA-funded Indiana Alzheimer’s Disease Center (IADC) protocol. We will complete 24-month imaging of these survivors (n=75) to assess post-acute effects. We will compare TLC survivor results to TLC non-cancer controls and published AD data, including those specific to women. The aims are to test hypotheses about associations between: 1) CRCD and clinical-pathological features of AD, 2) CRCD and established AD-risk factors, and 3) AD-related inflammatory markers and AD clinical- pathological features in CRCD and explore if inflammation mediates CRCD risk. This research is significant because we are looking at biological mechanisms for two important cognitive aging processes- CRCD and AD. We will advance NIA research goals by elucidating the impact of genetics and inflammatory processes on cognitive aging. This research is significant because cognitive aging has clinically important effects on daily life. We are not aware of any studies comparing CRCD and AD, and none that include an established collaboration of cancer, Alzheimer’s, and geriatrics investigators working together across silos. Overall, this study will move the field forward by determining potential bidirectional mechanisms between CRCD and AD.

抽象的 随着美国人口的年龄，了解认知衰老的异质性越来越重要 诸如阿尔茨海默氏病（AD）和与癌症相关的认知下降（CRCD）等病理状况。有 数据表明CRCD和AD具有重要的认知衰老特征。这个次要的目的 数据分析项目是为了测试较老的乳腺癌生存是否具有CRCD的临床病理特征 AD，包括广告病理学生物标志物异常，认知变化，大脑成像改变和类似 风险因素概况。为了实现这一目标，我们将使用现有的去识别数据和来自 癌症（TLC）研究队列的思想和生活。 TLC包括60岁的女性乳腺癌存活 98岁的人评估了预处理，每年最多60个月，数量相等 同时评估了非癌症对照（n = 700/组）。同意包括将来使用数据和 用于新研究目的的标本。研究较老的乳腺癌存活是合乎逻辑的，因为它们已经 面对认知衰老，CRCD在乳腺癌中最常被描述，冲浪者在年龄 范围范围内使用APOE-4开发AD的非癌人群，女性与男性的AD率更高，并且 35％的TLC表面表面基于明显的变化显着的变化已经具有全球认知能力下降 非癌症控件。纵向TLC数据包括关于记忆神经心理学测试的评分，执行 功能，语言和视觉能力；人口统计学；广告风险因素；和炎症标记（IL- 6，TNF-A，IL-8，IL-10，IFNG，CRP）。我们通过使用银行标本来测试血浆AD-添加这些数据 病理生物标志物（Aβ1-42，TAU，P-TAU和神经丝轻链[NFL]）和危险相关的分子 模式（潮湿：Aβ，S100蛋白质和HMBG1）。印第安纳大学的TLC表面表面的子集有 使用NIA资助的印第安纳州阿尔茨海默氏病中心（IADC）方案的基线和12个月MRI数据。 我们将完成这些表面的24个月成像（n = 75），以评估急性后效应。我们将比较 TLC表面的结果是TLC非癌症控制和发布的AD数据，包括特定于女性的数据。 目的是检验有关以下相关性的假设：1）CRCD和临床病理特征 AD，2）CRCD和已建立的广告风险因素，以及3）与广告相关的炎症标记和AD临床 - CRCD中的病理特征并探索感染是否介导CRCD风险。这项研究很重要 因为我们正在研究两个重要的认知衰老过程的生物学机制-CRCD和AD。 我们将通过阐明遗传学和炎症过程对NIA的研究目标来促进NIA研究目标 认知衰老。这项研究很重要，因为认知衰老对每日的临床重要影响 生活。我们不知道有任何比较CRCD和AD的研究，而没有一个包括已建立的研究 癌症，阿尔茨海默氏症和老年研究人员的合作在整个筒仓中共同工作。总体而言，这 研究将通过确定CRCD和AD之间的潜在双向机制来向前发展。