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

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 认知老化领域越来越关注识别早期认知衰退和过渡 从正常衰老到阿尔茨海默病（AD）的连续性。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影响， 其通常被定义为由于先前的测试暴露而导致的分数的改善。实践效果是 这对衰老的研究很重要，因为它们夸大了表现，从而掩盖了年龄的真实程度- 预期在中年和晚年会出现相关的认知能力下降。如果不纠正练习效果， 一项纵向研究可能表明，基于典型的基于规范的 损害的分类。虽然认知能力下降可能是一个持续的过程， 对于确定何时改变患者护理以及何时在研究中招募受试者是必要的。切割 认知障碍的点，就像生物标志物的分界点一样，是因为具有这种水平的个体， 表现更有可能有其他症状或疾病进展的可能性更大。的 认知变化的错误分类也可能模糊认知与生物标志物之间的关系， AD的危险因素然而，研究人员几乎总是利用未经校正的数据，依靠纯粹的统计数据， 练习的方法影响纠正，或简单地协变访问的数量。直接针对实践 在两个时间点的影响，一个更好的方法是包括替代受试者谁是幼稚的测试， 但在年龄和人口统计学上与回归者相匹配使用这种方法，越南时代的老化双胞胎研究 （VETSA），表现出六年后的实践效果，即使平均性能随年龄下降。 此外，练习效应矫正使轻度认知障碍（MCI）诊断的百分比增加了一倍 同时减少恢复正常的参与者数量。在本建议中，我将把这种方法扩展到 第一次在两个以上的评估中应用效果校正。数据将来自 VETSA和阿尔茨海默病神经影像学倡议（ADNI）在参与者年龄上有所不同， 间隔、生物标志物和评估次数。我现在有了鉴定“伪”的试点数据 ADNI中的替代受试者。该方法将在ANDI中开发，并在VETSA中交叉验证， 招募"真正的"替代实验对象我假设，考虑到实践效果， MCI的诊断，以及认知表现和生物标志物之间更强的信号。通过早期检测 研究人员和临床医生将能够更好地跟踪AD进展并监测MCI的有效性。 潜在的治疗。在目前的建议之外，一个更长远的目标是制定规范的做法效果 数据（例如，工具箱（toolbox）通过促进早期发现认知能力下降和进展为AD相关疾病， 规范性实践效果数据将对全国范围内的公共卫生产生重大影响。

项目成果

Cognitive Reserve and Related Constructs: A Unified Framework Across Cognitive and Brain Dimensions of Aging.

• DOI: 10.3389/fnagi.2022.834765
• 发表时间: 2022
• 期刊: Frontiers in aging neuroscience
• 影响因子: 4.8

Practice Effects in Mild Cognitive Impairment Increase Reversion Rates and Delay Detection of New Impairments.

• DOI: 10.3389/fnagi.2022.847315
• 发表时间: 2022
• 期刊: FRONTIERS IN AGING NEUROSCIENCE
• 影响因子: 4.8
• 作者: Sanderson-Cimino, Mark;Elman, Jeremy A.;Tu, Xin M.;Gross, Alden L.;Panizzon, Matthew S.;Gustavson, Daniel E.;Bondi, Mark W.;Edmonds, Emily C.;Eppig, Joel S.;Franz, Carol E.;Jak, Amy J.;Lyons, Michael J.;Thomas, Kelsey R.;Williams, McKenna E.;Kremen, William S.
• 通讯作者: Kremen, William S.

MRI-assessed locus coeruleus integrity is heritable and associated with multiple cognitive domains, mild cognitive impairment, and daytime dysfunction.

• DOI: 10.1002/alz.12261
• 发表时间: 2021-06
• 期刊: Alzheimer's & dementia : the journal of the Alzheimer's Association
• 作者: Elman JA;Puckett OK;Beck A;Fennema-Notestine C;Cross LK;Dale AM;Eglit GML;Eyler LT;Gillespie NA;Granholm EL;Gustavson DE;Hagler DJ Jr;Hatton SN;Hauger R;Jak AJ;Logue MW;McEvoy LK;McKenzie RE;Neale MC;Panizzon MS;Reynolds CA;Sanderson-Cimino M;Toomey R;Tu XM;Whitsel N;Williams ME;Xian H;Lyons MJ;Franz CE;Kremen WS
• 通讯作者: Kremen WS

Independent and Synergistic Associations Between TBI Characteristics and PTSD Symptom Clusters on Cognitive Performance and Postconcussive Symptoms in Iraq and Afghanistan Veterans.

伊拉克和阿富汗退伍军人的 TBI 特征和 PTSD 症状群对认知表现和脑震荡后症状的独立和协同关联。

• DOI: 10.1176/appi.neuropsych.20050128
• 发表时间: 2021
• 期刊: The Journal of neuropsychiatry and clinical neurosciences
• 作者: Jurick,SarahM;Crocker,LauraD;Merritt,VictoriaC;Sanderson-Cimino,MarkE;Keller,AmberV;Glassman,LisaH;Twamley,ElizabethW;Rodgers,CarieS;Schiehser,DawnM;Aupperle,RobinL;Jak,AmyJ
• 通讯作者: Jak,AmyJ