Jauregi-Zinkunegi Ainara, Betthauser Tobey, Carlsson Cynthia M, Bendlin Barbara B, Okonkwo Ozioma, Chin Nathaniel A, Asthana Sanjay, Langhough Rebecca E, Johnson Sterling C, Mueller Kimberly D, Bruno Davide
School of Psychology, Liverpool John Moores University, United Kingdom.
Wisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA; Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA; Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Cortex. 2025 Mar;184:47-57. doi: 10.1016/j.cortex.2024.12.012. Epub 2025 Jan 3.
Alzheimer's disease (AD) can be diagnosed by in vivo abnormalities of amyloid-β plaques (A) and tau accumulation (T) biomarkers. Previous studies have shown that analyses of serial position performance in episodic memory tests, and especially, delayed primacy, are associated with AD pathology even in individuals who are cognitively unimpaired. The earliest signs of cortical tau pathology are observed in medial temporal lobe (MTL) regions, yet it is unknown if serial position markers are also associated with early tau load in these regions. This study of cognitively unimpaired older individuals examined whether serial position scores in word-list recall cross-sectionally predicted tau PET load in the MTL, and were able to discriminate between biomarker profiles, based on AT classification.
Data from 490 participants (mean age = 68.8 ± 7.2) were extracted from two cohorts, which were merged into one sample. Linear regression analyses were carried out with regional volume-controlled tau (18F-MK-6240) PET SUVR of the entorhinal cortex (EC), parahippocampal cortex (PHC) and hippocampus (H) as outcomes, cross-sectional memory scores from the Rey Auditory Verbal Learning Test as predictors (total and delayed recall, along with serial position scores) and control variables, in separate analyses for each outcome and predictor. The sample was then stratified by biomarker profile and ANCOVAs were conducted with the strongest scores from the regression analyses, AT groups as fixed factor and the covariates.
Higher delayed primacy significantly predicted lower tau PET in EC, PHC, and H, cross-sectionally. Higher total recall scores predicted lower EC tau, but delayed primacy showed the best model fit, as indicated by AICs. ANCOVAs showed that AVLT metrics did not significantly discriminate between A-T- and A+T+, after correcting for multiple comparisons.
Serial position analysis of word-list recall, particularly delayed primacy, may be a valuable tool for identifying in vivo tau pathology in cognitively unimpaired individuals.
阿尔茨海默病（AD）可通过体内淀粉样β斑块（A）和tau蛋白积聚（T）生物标志物的异常来诊断。先前的研究表明，情景记忆测试中的系列位置表现分析，尤其是延迟首因效应，即使在认知未受损的个体中也与AD病理相关。皮质tau蛋白病理的最早迹象出现在内侧颞叶（MTL）区域，但尚不清楚系列位置标记是否也与这些区域的早期tau蛋白负荷相关。这项针对认知未受损老年人的研究，考察了单词列表回忆中的系列位置得分是否能横断面预测MTL中的tau蛋白PET负荷，以及是否能够根据AT分类区分生物标志物特征。
从两个队列中提取了490名参与者（平均年龄=68.8±7.2）的数据，并合并为一个样本。以内嗅皮质（EC）、海马旁皮质（PHC）和海马体（H）的区域体积控制的tau蛋白（18F-MK-6240）PET标准化摄取值比（SUVR）为结果变量，以雷伊听觉词语学习测验的横断面记忆得分作为预测变量（总回忆和延迟回忆，以及系列位置得分）和控制变量，对每个结果变量和预测变量进行单独分析。然后根据生物标志物特征对样本进行分层，并使用回归分析中最强的得分进行协方差分析，将AT组作为固定因素和协变量。
横断面分析显示，较高的延迟首因效应显著预测了EC、PHC和H中较低的tau蛋白PET。较高的总回忆得分预测了较低的EC tau蛋白，但如AIC所示，延迟首因效应显示出最佳的模型拟合。协方差分析表明，在校正多重比较后，AVLT指标在A-T-和A+T+之间没有显著差异。
单词列表回忆的系列位置分析，尤其是延迟首因效应，可能是识别认知未受损个体体内tau蛋白病理的有价值工具。
