Effect of baseline and intercurrent medical factors on 6-year cognitive trajectory: Secondary analysis of the SAGES Study

基线和并发医疗因素对 6 年认知轨迹的影响：SAGES 研究的二次分析

• 批准号: 10545760
• 负责人: Tammy T Hshieh
• 金额: $ 15.98万
• 依托单位: HEBREW REHABILITATION CENTER FOR AGED
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-15 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10545760
• 关键词: Acceleration; Acute; Address; Age; Aging; Algorithms; Alleles; Alzheimer' s disease related dementia; Anti-Inflammatory Agents; Area; Biological Markers; Brain; C-reactive protein; Cessation of life; Chitinase; Chronic Disease; Clinical; Cognitive; Cognitive aging; Confusion; Data; Data Analyses; Databases; Delirium; Dementia; Development; Disease; Elderly; Event; Exposure to; Foundations; Frequencies; Future; Genetic Risk; Geriatric Assessment; Hemodialysis; Hospitalization; Hospitals; Hypoxia; Impaired cognition; Individual; Inflammatory; Interleukin-6; Intervention; Investigation; Kidney Failure; Laboratories; Liver Failure; Measures; Medical; Medical Records; Medicare; Mentors; Metabolic; Neuropsychological Tests; Operative Surgical Procedures; Pathologic; Pathway interactions; Patients; Persons; Postoperative Period; Predisposition; Prevention; Procedures; Process; Prospective Studies; Proteins; Recurrence; Research; Research Personnel; Research Project Grants; Risk Factors; Sampling; Signal Transduction; Stroke; Time; Work; apolipoprotein E-4; career; chemotherapy; cognitive function; cohort; disorder prevention; experience; follow-up; indexing; innovation; mild cognitive impairment; next generation; postoperative delirium; programs; response; secondary analysis; skills; stressor; success

Responding to PAS-19-391, this proposal will leverage existing data to advance our understanding of Alzheimer’s disease and related dementias (AD/ADRD) and to nurture the career of a promising early stage investigator, Dr. Tammy Hshieh. This proposal will use data drawn from a clinically rich cohort, the Successful Aging after Elective Surgery (SAGES), involving 560 older adults (age 70+) without clinical dementia evaluated prior to major elective surgery and followed for 6 years with repeated neuropsychological testing. We plan to explore a priority area in the PA: ‘to advance our understanding of how cognitive function may change from normal to pathological cognitive aging’, which we here define broadly as including both AD- and ADRD-related processes. SAGES has collected data on intercurrent illnesses, hospitalizations, surgeries, and major treatments (e.g., chemotherapy, hemodialysis) for up to 6 years. We propose to evaluate the effects of these intercurrent factors on cognitive trajectory, along with the moderating effects of delirium and/or ApoE-E4 status, which may serve as markers of brain vulnerability. Our specific aims are: (1) To evaluate the effect of intercurrent medical factors on cognitive trajectory for up to 6 years: We will examine factors first singly then cumulatively with the hypothesis that certain factors will have greater decrements considered singly and that a higher number of factors will result in a steeper slope of decline over time, achieving rates of decline comparable to MCI or early AD/ADRD. (2) To examine the effect of abnormal baseline laboratory results and inflammatory biomarkers (e.g., C-reactive protein, interleukin-6) on cognitive trajectory: We hypothesize that a higher number of abnormal laboratory values and/or biomarkers will have a highest rate of cognitive decline, achieving rates of decline comparable to MCI or early AD/ADRD. (3) To elucidate whether development of delirium and/or genetic risk (ApoE-E4 status) moderates the association of major intercurrent factors or abnormal laboratory- or bio- markers, either singly or cumulatively, on cognitive trajectory. Our analyses will utilize an innovative longitudinal data analysis approach with time-varying predictors to generate a weighting algorithm for a dynamic index (an index that can change within a person over time), representing the cumulative effect of potential cognitive insults. We have demonstrated adequate statistical power to achieve our aims. Success of the proposed work is further assured by a highly skilled interdisciplinary team who have been close collaborators for over 10 years, and who will mentor Dr. Hshieh. This project will help to identify intercurrent factors or abnormal laboratory- or bio- markers that may lead to cognitive decline, particularly in those individuals with more vulnerable brains, as signaled by ApoE-E4 or by development of delirium. Understanding these factors will help us to identify potential pathways which might transform normal to pathological cognitive aging. Such understanding will advance our pathophysiologic understanding, and lay the groundwork for future targeted intervention strategies.

针对 PAS-19-391，该提案将利用现有数据来加深我们对 阿尔茨海默病和相关痴呆症（AD/ADRD）并培养有前途的早期职业 研究员 Tammy Hshieh 博士。该提案将使用从临床丰富的队列中提取的数据，即成功的队列 择期手术后老化 (SAGES)，对 560 名没有临床痴呆的老年人（70 岁以上）进行了评估 在重大择期手术之前进行，并进行为期 6 年的重复神经心理学测试。我们计划 探索 PA 的一个优先领域：“加深我们对认知功能如何从 正常到病理性认知衰老”，我们在这里将其广泛定义为包括 AD 和 ADRD 相关的 流程。 SAGES 收集了有关并发疾病、住院、手术和重大疾病的数据 治疗（例如化疗、血液透析）长达 6 年。我们建议评估这些措施的影响 对认知轨迹的并发因素，以及谵妄和/或 ApoE-E4 状态的调节作用， 这可能作为大脑脆弱性的标志。 我们的具体目标是：（1）评估并发医疗因素对认知轨迹的影响 到 6 年：我们将首先单独检查因素，然后累积地检查因素，假设某些因素将 单独考虑时会有更大的减量，并且更多数量的因素将导致更陡的斜率 随着时间的推移而下降，达到与 MCI 或早期 AD/ADRD 相当的下降率。 (2) 检验效果 异常基线实验室结果和炎症生物标志物（例如 C 反应蛋白、白细胞介素 6） 认知轨迹：我们假设更多数量的异常实验室值和/或生物标志物将 认知能力下降率最高，下降率与 MCI 或早期 AD/ADRD 相当。 (3) 阐明谵妄的发生和/或遗传风险（ApoE-E4 状态）是否会调节这种关联 主要并发因素或异常实验室或生物标志物（单独或累积）对认知的影响 弹道。我们的分析将利用创新的纵向数据分析方法和时变数据 预测器为动态指数（可以在一个人体内改变的指数）生成加权算法 随着时间的推移），代表潜在认知侮辱的累积效应。我们已经证明了足够的 实现我们目标的统计能力。高技能人员进一步保证了拟议工作的成功 跨学科团队，他们一直是 10 多年的密切合作者，并将指导 Hshieh 博士。 该项目将有助于识别并发因素或异常实验室或生物标志物，这些因素可能导致 认知能力下降，特别是那些大脑更脆弱的人，如 ApoE-E4 或 谵妄的发展。了解这些因素将有助于我们识别可能的潜在途径 将正常认知衰老转变为病理性认知衰老。这种理解将促进我们的病理生理学 的认识，为今后有针对性的干预策略奠定基础。