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: 10408070
• 负责人: Jeanne Mandelblatt
• 金额: $ 67.21万
• 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 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10408070
• 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; 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 (Brain); Hormonal; Hormone use; IL8 gene; Image; Impaired cognition; Impairment; Indiana; Individual; Inflammation; Inflammatory; Interleukin-10; Interleukin-6; Language; Late Onset Alzheimer Disease; Lead; 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; apolipoprotein E-4; base; 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; 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 随着美国人口老龄化，了解认知老龄化的异质性变得越来越重要，包括 阿尔茨海默病 (AD) 和癌症相关认知能力下降 (CRCD) 等病理状况。 数据表明 CRCD 和 AD 具有重要的认知衰老特征。 数据分析项目旨在测试患有 CRCD 的老年乳腺癌幸存者是否具有以下临床病理特征： AD，包括 AD 病理生物标志物异常、认知变化、脑成像改变等 为了实现这一目标，我们将使用现有的去识别化数据和存储的样本。 癌症思考与生活 (TLC) 研究队列包括 60 岁以上的女性乳腺癌幸存者。 98 岁的老人在治疗前进行评估，每年进行长达 60 个月的评估，并进行同等数量的评估 同时评估非癌症对照（n=700/组），同意包括未来使用数据和 研究老年乳腺癌幸存者的样本是合乎逻辑的，因为他们已经是了。 面对认知老化，CRCD最常被描述为乳腺癌，幸存者处于年龄 携带 APOE-4 的非癌症人群患 AD 的范围，女性 AD 发生率高于男性，并且 35% 的 TLC 幸存者已经出现整体认知能力下降，其变化明显大于 非癌症对照的纵向 TLC 数据包括记忆、执行能力的神经心理学测试分数。 功能、语言和视觉空间能力；AD 危险因素； 我们通过使用储存的样本来测试血浆 AD-来添加这些数据。 病理生物标志物（Aβ1-42、tau、p-tau 和神经丝轻链 [NFL]）和危险相关分子 印第安纳大学 TLC 幸存者的一个子集具有模式（DAMP：Aβ、S100 蛋白和 HMBG1）。 使用 NIA 资助的印第安纳阿尔茨海默病中心 (IADC) 协议获取基线和 12 个月 MRI 数据。 我们将对这些幸存者 (n=75) 进行 24 个月的成像，以评估急性后的影响。 TLC 幸存者结果与 TLC 非癌症对照和已发布的 AD 数据（包括针对女性的数据）一致。 目的是检验以下之间关联的假设：1) CRCD 与临床病理特征 AD，2) CRCD 和已确定的 AD 危险因素，以及 3) AD 相关炎症标志物和 AD 临床- 探讨CRCD的病理特征并探讨炎症是否介导CRCD风险。 因为我们正在研究两个重要的认知衰老过程——CRCD 和 AD 的生物机制。 我们将通过阐明遗传学和炎症过程对 NIA 的影响来推进 NIA 研究目标 这项研究意义重大，因为认知衰老对日常生活具有重要的临床影响。 我们不知道有任何比较 CRCD 和 AD 的研究，也没有包含已确定的研究。 癌症、阿尔茨海默病和老年病学研究人员跨领域合作。 研究将通过确定 CRCD 和 AD 之间潜在的双向机制来推动该领域的发展。