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

项目总结 认知老化领域越来越关注识别早期认知衰退和转换 从正常衰老到阿尔茨海默病(AD)的连续体。纵向评估是必要的 来监测认知变化。然而，涉及重复测试的研究受到实践效果的影响， 这通常被定义为由于先前的测试暴露而导致的分数提高。练习的效果是 对衰老的研究很重要，因为它们夸大了性能，从而掩盖了年龄的真实程度- 预计中老年会出现相关的认知衰退。如果没有针对练习效果进行校正，则在 一项纵向研究可能表明，基于典型常模的认知能力下降不会被发现 减损的分类。尽管认知能力下降可能是一个持续的过程，但 损伤是决定何时改变患者护理和何时将受试者纳入研究的必要因素。切 认知障碍的临界点，就像生物标记物的临界点一样，是因为具有这种水平的个人 表现出其他症状的可能性更大，或者疾病进展的可能性更大。这个 对认知变化的错误分类也可能模糊认知和生物标记物之间的关系 AD的危险因素。然而，研究人员几乎总是使用未经更正的数据，纯粹依靠统计学 练习效果矫正的方法，或简单地根据就诊次数的不同而变化。直接面对实践 跨两个时间点的影响，更好的方法是包括对测试天真的替代受试者， 但年龄--和人口统计--与海归相匹配。使用这种方法，越南时代的双胞胎老龄化研究 (Vetsa)，六年后表现出练习效果，即使平均成绩随着年龄的增长而下降。 此外，练习效果纠正使轻度认知障碍(MCI)的诊断百分比翻了一番 同时减少恢复正常的参与者数量。在这项提议中，我将把这种方法扩展到 通过第一次将其应用于两个以上的评估来练习效果校正。数据将来自 Vetsa和阿尔茨海默病神经成像计划(ADNI)，这两项在参与者年龄上不同的测试，重新测试 时间间隔、生物标志物和评估次数。我现在有关于识别“伪”的试点数据 ADNI中的替代对象。该方法将在Andi内开发，并在Vetsa交叉验证， 招募了“真正的”替补对象。我假设，考虑到实践的影响将导致更早 MCI的诊断，以及认知能力和生物标记物之间更强的信号。具有更早的检测 MCI的研究人员和临床医生将能够更好地跟踪AD的进展并监测 潜在的治疗方法。在目前的提案之外，一个较长期的目标是发展规范实践的效果 数据(例如，使用NIH工具箱)。通过促进认知功能下降和进展为AD相关疾病的早期检测 在精神障碍方面，规范性实践效果数据将对全国公共卫生产生重大影响。

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.