Smegal Lindsay F, Baillet Marion, Schneider Christoph, Jutten Roos J, Boyle Rory, Rentz Dorene M, Johnson Keith A, Sperling Reisa A, Papp Kathryn V, Jacobs Heidi I L
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Department of Psychology, Georgia State University, Atlanta, GA 30303, USA.
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Neurobiol Aging. 2025 Aug;152:13-24. doi: 10.1016/j.neurobiolaging.2025.03.015. Epub 2025 Apr 26.
The locus coeruleus (LC), one of the earliest structures affected by tau pathology in Alzheimer's disease (AD), plays an important role in modulating arousal and learning. In asymptomatic early stages of AD, more sensitive measures to identify subtle cognitive changes are needed. Previous studies indicate that practice effects can signal initial AD-related learning deficits. Here, we assessed the association between LC integrity and practice effects. We combined dedicated LC-MRI methods with at-home computerized face-name letter task (FNLT), a Mnemonic Similarity Task (MST), and a one card learning task (OCL) performed monthly over one year in 76 older participants from the Harvard Aging Brain Study. Higher LC integrity was related to lower MST reaction times at baseline, and lower MST and FNLT reaction times over one year. No significant associations were found with the OCL. Participants with low accuracy practice effect trajectories exhibited low baseline PACC-5 scores, whereas those with higher reaction times over time displayed low LC integrity, high entorhinal, and high amygdala tau at baseline. These findings suggest reaction times measured monthly may be a sensitive measure for early AD-related biomarkers such as LC integrity and tau burden in preclinical AD.
蓝斑（LC）是阿尔茨海默病（AD）中最早受tau病理影响的结构之一，在调节觉醒和学习方面发挥着重要作用。在AD的无症状早期阶段，需要更敏感的测量方法来识别细微的认知变化。先前的研究表明，练习效应可以预示最初与AD相关的学习缺陷。在此，我们评估了LC完整性与练习效应之间的关联。我们将专门的LC-MRI方法与一项在家进行的电脑化面孔-姓名字母任务（FNLT）、一项记忆相似性任务（MST）以及一项单卡学习任务（OCL）相结合，该任务在来自哈佛衰老大脑研究的76名老年参与者中进行，为期一年，每月进行一次。较高的LC完整性与基线时较低的MST反应时间以及一年中较低的MST和FNLT反应时间相关。未发现与OCL有显著关联。练习效应轨迹准确性低的参与者基线时PACC-5得分低，而随着时间推移反应时间较长的参与者基线时LC完整性低、内嗅区tau高且杏仁核tau高。这些发现表明，每月测量的反应时间可能是早期AD相关生物标志物（如临床前AD中的LC完整性和tau负担）的敏感测量指标。
