Practice Effects in Cognitive Aging: Implications for Biomarkers and Early Diagnosis

认知衰老的实践效果：对生物标志物和早期诊断的影响

• 批准号: 10295029
• 负责人: Mark Sanderson-Cimino
• 金额: $ 3.98万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10295029
• 关键词: Accounting; Address; Adopted; Affect; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Alzheimer' s disease patient; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Biological Markers; Classification; Clinical; Clinical Trials; Cognition; Cognitive; Cognitive aging; Cognitive deficits; Cost of Illness; Data; Data Set; Dementia; Detection; Deterioration; Development; Diagnosis; Diagnostic; Disease; Disease Progression; Early Diagnosis; Early identification; Education; Effectiveness; Elderly; Enrollment; Exposure to; Financial Hardship; Future; Goals; Health Benefit; Heterogeneity; Impaired cognition; Impairment; Individual; Longitudinal Studies; Masks; Memory impairment; Methods; Modeling; Monitor; Noise; Participant; Patient Care; Performance; Pharmaceutical Preparations; Population; Process; Public Health; Quality of life; Research; Research Design; Research Personnel; Risk; Risk Factors; Signal Transduction; Statistical Methods; Sum; Symptoms; Testing; Time; Twin Studies; United States National Institutes of Health; Vietnam; Visit; accurate diagnosis; age related; aged; base; clinically relevant; cognitive ability; cognitive change; cognitive performance; cognitive testing; cohort; cost effective; improved; middle age; mild cognitive impairment; neuroimaging; normal aging; novel; pathological aging; performance tests; prevent; recruit; Accounting; Address; Adopted; Affect; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Alzheimer' s disease patient; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Biological Markers; Classification; Clinical; Clinical Trials; Cognition; Cognitive; Cognitive aging; Cognitive deficits; Cost of Illness; Data; Data Set; Dementia; Detection; Deterioration; Development; Diagnosis; Diagnostic; Disease; Disease Progression; Early Diagnosis; Early identification; Education; Effectiveness; Elderly; Enrollment; Exposure to; Financial Hardship; Future; Goals; Health Benefit; Heterogeneity; Impaired cognition; Impairment; Individual; Longitudinal Studies; Masks; Memory impairment; Methods; Modeling; Monitor; Noise; Participant; Patient Care; Performance; Pharmaceutical Preparations; Population; Process; Public Health; Quality of life; Research; Research Design; Research Personnel; Risk; Risk Factors; Signal Transduction; Statistical Methods; Sum; Symptoms; Testing; Time; Twin Studies; United States National Institutes of Health; Vietnam; Visit; accurate diagnosis; age related; aged; base; clinically relevant; cognitive ability; cognitive change; cognitive performance; cognitive testing; cohort; cost effective; improved; middle age; mild cognitive impairment; neuroimaging; normal aging; novel; pathological aging; performance tests; prevent; recruit

PROJECT SUMMARY The field of cognitive aging is increasingly concerned with identifying early cognitive decline and the transition point from normal aging to the Alzheimer’s Disease (AD) continuum. Longitudinal assessments are necessary to monitor cognitive change. However, studies that involve repeated testing are subject to practice effects, which are typically defined as improvements in scores because of prior test exposure. Practice effects are important for studies of aging because they inflate performance, thereby obscuring the true degree of age- related cognitive decline expected at mid- and late life. If uncorrected for practice effects, stable performance in a longitudinal study may indicate cognitive decline that would go undetected based on typical norm-based classifications of impairment. Although cognitive decline is a likely a continuous process, cut points for impairment are necessary for determining when to alter patient care and when to enroll subjects in a study. Cut points for cognitive impairment, like cut points for biomarkers, are set because individuals with that level of performance are more likely to have other symptoms or a greater likelihood for disease progression. The misclassification of cognitive change may also obscure the relationship between cognition and biomarkers or risk factors for AD. Nevertheless, researchers almost always utilize uncorrected data, rely on purely statistical methods of practice effect correction, or simply covary for the number of visits. To directly address practice effects across two timepoints, a better method is to include replacement subjects who are naive to the tests, but age- and demographically-matched to returnees. Using this method, the Vietnam Era Twin Study of Aging (VETSA), demonstrated practice effects after six years, even when mean performance declined with age. Moreover, practice effect correction doubled the percentage of mild cognitive impairment (MCI) diagnoses while reducing the number of participants who reverted to normal. In this proposal I will extend this approach to practice effect correction by, for the first time, applying it across more than two assessments. Data will be from the VETSA and the Alzheimer’s Disease Neuroimaging Initiative (ADNI), which differ in participant age, retest interval, biomarkers, and number of assessments. I now have pilot data on the identification of “pseudo” replacement subjects in ADNI. The method will be developed within ANDI and cross-validated in VETSA, which recruited “true” replacement subjects. I hypothesize that accounting for practice effects will lead to earlier diagnoses of MCI, and a stronger signal between cognitive performance and biomarkers. With earlier detection of MCI, researchers and clinicians will be better able to track AD progression and monitor the effectiveness of potential treatments. Beyond the current proposal, a longer-term goal is to develop normative practice effect data (e.g., with NIH toolbox). By promoting earlier detection of cognitive decline and progression to AD-related disorders, normative practice effect data would have substantial nationwide public health implications.

项目摘要 认知衰老的领域越来越关注确定早期认知能力下降和过渡 从正常衰老到阿尔茨海默氏病（AD）的点仍在继续。纵向评估是必要的 监测认知变化。但是，涉及重复测试的研究可能会受到实践效应， 由于先前的测试暴露，通常定义为得分的改进。实践效果是 对于衰老的研究很重要，因为它们会膨胀性能，从而掩盖了真正的年龄程度 - 相关的认知能力下降在中期和晚期。如果未纠正练习效果，则稳定的表现 一项纵向研究可能表明认知能力下降，基于典型规范 损害的分类。尽管认知能力下降可能是一个连续的过程，但 损害对于确定何时改变患者护理以及何时将受试者注册研究是必要的。切 认知障碍的点（例如生物标志物的切点）之所以设定，是因为具有该水平的个人 表现更有可能具有其他症状或疾病进展的可能性更大。这 对认知变化的错误分类也可能掩盖认知与生物标志物之间的关系或 AD的风险因素。然而，研究人员几乎总是利用未校正的数据，依靠纯粹的统计 练习效果校正的方法，或仅用于访问次数的共同体。直接解决实践 在两个时间点上的效果，一种更好的方法是包括对测试天真的替换对象， 但是年龄和人口统计学匹配的回报。使用这种方法，越南时代的衰老研究 （VETSA），即使平均表现随着年龄的增长而下降，也证明了练习效果。 此外，实践效果校正使轻度认知障碍（MCI）诊断的百分比增加了一倍 同时减少恢复正常的参与者人数。在此提案中，我将把这种方法扩展到 练习效应校正首次将其应用于两个以上的评估。数据将来自 VETSA和阿尔茨海默氏病神经影像学计划（ADNI），参与者年龄不同，重新测试 间隔，生物标志物和评估数量。我现在有有关识别“伪”的试点数据 ADNI中的替换对象。该方法将在Andi内开发，并在Vetsa中进行交叉验证， 招募了“真实”替代主题。我假设考虑实践效果会导致更​​早的练习效果 MCI的诊断，认知性能和生物标志物之间的信号更强。与较早的检测 在MCI中，研究人员和临床医生将更好地跟踪AD的进度并监测 潜在治疗。除了目前的提议之外，一个长期目标是制定正常实践效果 数据（例如，使用NIH工具箱）。通过促进早期发现认知能力下降和发展为与广告相关的 疾病，正常实践效果数据将具有重大的国家健康影响。